Abstract: A highly efficient and milder protocol for the syntheses of novel series of 2-aminothiazoles
bearing 5-methylisoxazoline and pyridine-piperazine hybrid molecules has been developed. The target
compounds 13a-e were screened for their in vitro cytotoxicity activity against various tumor cell lines
including MCF-7 (human breast adenocarcinoma), HCT-116 (colorectal carcinoma), Jurkat (human Tcell
leukemia) and THP-1 (human acute monocytic leukemia). The bioactive assay showed most of the
new compounds exhibited promising results in comparison with the parental Sunitinib. The synthesized
compounds could well be used in the future as lead anticancer drugs in drug development studies. The
synthesized compounds were fully characterized by IR, 1H NMR, 13C NMR, elemental analysis and
mass spectral data.
The herbicide residue from intensive agricultural
activity provokes environmental disturbances and human health injuries. Among the enzymatic disruptor herbicides, mesotrione is able to inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD), which plays a key role in the carotenoid synthesis. Therefore, enzyme-based sensors are innovative options for monitoring herbicides used in agriculture.
SOCIAL AND ECONOMIC BURDEN OF CANCER ON 2020- REVIEW Tamizhazhagan, Pugazh...Earthjournal Publisher
SOCIAL AND ECONOMIC BURDEN OF CANCER ON 2020- REVIEW
Tamizhazhagan, Pugazhendy, Sakthidasan, Jayanthi, Ki-Hyun Kim
IRO INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES 2018, 1(1):24-30.
Research Avenues in Drug discovery of natural productsDevakumar Jain
This document discusses challenges facing the pharmaceutical industry and opportunities for natural products in drug discovery. The pharmaceutical industry faces losses of patent protection for many drugs, increasing costs, and litigation. Natural products are attractive alternatives as they have evolved to be bioactive and have structures not limited by human design. Advances like high-throughput screening, metabolomics, metagenomics, and metabolic engineering can help access natural product diversity and accelerate drug discovery from natural sources.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
This document discusses lectin-mediated drug delivery and therapeutics. It begins by introducing the concept of using lectins to specifically target drug delivery systems to sites via direct or reverse targeting based on unique carbohydrate moieties. It then discusses different approaches to lectin-based drug targeting including using prodrugs and conjugating drugs to lectins. Specific examples of lectins that have potential for cancer therapy are also provided. The document concludes by briefly mentioning the use of carbohydrates in vaccines and anti-adhesion therapeutics.
Toxicological advances of traditional medicine in 2019LucyPi1
1. The paper reviewed toxicology research on traditional medicine from 2019. It found that the liver, kidney, and heart are mainly targeted for toxicity.
2. Safety research has also focused on different populations like infants, children, and those who are pregnant. Zebrafish embryos are now commonly used in addition to rodents to evaluate safety.
3. New technologies in 2019 included using multispectral optoacoustic tomography to image liver injury and integrating microRNA profiles to explain toxicity mechanisms. Overall research continues to improve understanding of toxicity targets and mechanisms.
The document discusses the history and importance of pharmacogenetics in understanding variability in individual drug response and toxicity. It describes the role of genetic polymorphisms in drug metabolizing enzymes like CYP450 and how this impacts drug clearance and effects. While data on genetic variability is growing, well-designed clinical trials are still needed to validate pharmacogenetic approaches and address the challenges of predicting drug metabolism and response based on genetics. Understanding these factors can help optimize drug therapy and dosing for individual patients.
Herbal and Synthetic Drug Combinations in Cancer Therapy A Reviewijtsrd
Cancer is one of the leading and most serious diseases in the current decade, every year millions of people die because of various kinds of cancers. Many aspects relate to the cause of disease besides heredity, food habits, smoking, nutritional behaviors, radiation etc. Cancer is a high mortality disease and the therapeutics for cancer, especially for cancer metastasis is still imperfect. The successful cancer treatment till now has been under study, only chemotherapy and radiation treatments are at times successful. Alternative and less toxic medication is very much in need towards the disease, the use of concepts of herbal medicine with synthetic drug could present better drug leads towards the inhibitory treatment of Cancer. Nature shows plethora of medicinal plants with anticancer and antioxidant activities which may suppress the disease completely. By applying combination therapy instead of monotherapy can lead to improved efficacy and reduced toxicity of the conventional method of treatments of cancer. Anusree S | Dr. Silvia Navis A | Dr. Prashob G R "Herbal and Synthetic Drug Combinations in Cancer Therapy- A Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd25222.pdfPaper URL: https://www.ijtsrd.com/pharmacy/pharmacology-/25222/herbal-and-synthetic-drug-combinations-in-cancer-therapy--a-review/anusree-s
The herbicide residue from intensive agricultural
activity provokes environmental disturbances and human health injuries. Among the enzymatic disruptor herbicides, mesotrione is able to inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD), which plays a key role in the carotenoid synthesis. Therefore, enzyme-based sensors are innovative options for monitoring herbicides used in agriculture.
SOCIAL AND ECONOMIC BURDEN OF CANCER ON 2020- REVIEW Tamizhazhagan, Pugazh...Earthjournal Publisher
SOCIAL AND ECONOMIC BURDEN OF CANCER ON 2020- REVIEW
Tamizhazhagan, Pugazhendy, Sakthidasan, Jayanthi, Ki-Hyun Kim
IRO INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES 2018, 1(1):24-30.
Research Avenues in Drug discovery of natural productsDevakumar Jain
This document discusses challenges facing the pharmaceutical industry and opportunities for natural products in drug discovery. The pharmaceutical industry faces losses of patent protection for many drugs, increasing costs, and litigation. Natural products are attractive alternatives as they have evolved to be bioactive and have structures not limited by human design. Advances like high-throughput screening, metabolomics, metagenomics, and metabolic engineering can help access natural product diversity and accelerate drug discovery from natural sources.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
This document discusses lectin-mediated drug delivery and therapeutics. It begins by introducing the concept of using lectins to specifically target drug delivery systems to sites via direct or reverse targeting based on unique carbohydrate moieties. It then discusses different approaches to lectin-based drug targeting including using prodrugs and conjugating drugs to lectins. Specific examples of lectins that have potential for cancer therapy are also provided. The document concludes by briefly mentioning the use of carbohydrates in vaccines and anti-adhesion therapeutics.
Toxicological advances of traditional medicine in 2019LucyPi1
1. The paper reviewed toxicology research on traditional medicine from 2019. It found that the liver, kidney, and heart are mainly targeted for toxicity.
2. Safety research has also focused on different populations like infants, children, and those who are pregnant. Zebrafish embryos are now commonly used in addition to rodents to evaluate safety.
3. New technologies in 2019 included using multispectral optoacoustic tomography to image liver injury and integrating microRNA profiles to explain toxicity mechanisms. Overall research continues to improve understanding of toxicity targets and mechanisms.
The document discusses the history and importance of pharmacogenetics in understanding variability in individual drug response and toxicity. It describes the role of genetic polymorphisms in drug metabolizing enzymes like CYP450 and how this impacts drug clearance and effects. While data on genetic variability is growing, well-designed clinical trials are still needed to validate pharmacogenetic approaches and address the challenges of predicting drug metabolism and response based on genetics. Understanding these factors can help optimize drug therapy and dosing for individual patients.
Herbal and Synthetic Drug Combinations in Cancer Therapy A Reviewijtsrd
Cancer is one of the leading and most serious diseases in the current decade, every year millions of people die because of various kinds of cancers. Many aspects relate to the cause of disease besides heredity, food habits, smoking, nutritional behaviors, radiation etc. Cancer is a high mortality disease and the therapeutics for cancer, especially for cancer metastasis is still imperfect. The successful cancer treatment till now has been under study, only chemotherapy and radiation treatments are at times successful. Alternative and less toxic medication is very much in need towards the disease, the use of concepts of herbal medicine with synthetic drug could present better drug leads towards the inhibitory treatment of Cancer. Nature shows plethora of medicinal plants with anticancer and antioxidant activities which may suppress the disease completely. By applying combination therapy instead of monotherapy can lead to improved efficacy and reduced toxicity of the conventional method of treatments of cancer. Anusree S | Dr. Silvia Navis A | Dr. Prashob G R "Herbal and Synthetic Drug Combinations in Cancer Therapy- A Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd25222.pdfPaper URL: https://www.ijtsrd.com/pharmacy/pharmacology-/25222/herbal-and-synthetic-drug-combinations-in-cancer-therapy--a-review/anusree-s
Annual advances of traditional medicine toxicity in 2018LucyPi1
Abstract There were many researches concerning toxicology of traditional medicine (TM) and active natural products during the past 12 months. This annual toxicology review summarized different analysis methods of toxicology research, common evaluated models, toxic target organs, toxic mechanisms, and popular research issues and herbs in 2018. The emphasis was on hepatorenal toxicity induced by TM through cell apoptosis, metabolic disorder, oxidative stress, inflammatory damage, liver and renal fibrosis and even inducing carcinogenesis. Meanwhile, traditional herbs were listed in this review. Taken together, the herbs mentioned in this paper should be used with caution. Combination of TM, processing drugs, quality control and dose control can be used in the prevention of TM toxicology in the future.
Cheminformatics is an interdisciplinary field that combines chemistry, biology, physics, mathematics, and computer science to manage chemical data and information. It plays a key role in processing the enormous amount of chemical data produced by chemists, maintaining databases, and extracting knowledge from data to model relationships between compound structure and biological activity. Cheminformatics has three major aspects: information acquisition, information management, and information use. It complements bioinformatics by addressing molecular processes like protein structure and function.
This document discusses the concept of endogenous toxicology, which examines pathological conditions from the perspective of toxins produced within the body. It provides several examples:
- Certain neurological diseases may be related to endogenous toxins similar to plant toxins, interacting with receptors evolved in response to environmental toxins.
- Metabolic diseases like diabetes and cardiovascular disease involve the accumulation of endogenous toxic molecules like advanced glycation end products.
- Cancer progression may be influenced by the local microenvironment in organs, with factors like blood flow affecting the likelihood of metastasis to specific sites.
- Many conditions could involve an imbalance or overproduction of endogenous substances acting as toxins in the body. This perspective could provide new approaches to treatment.
This document provides information about a project on waste water treatment in a pharmaceutical factory conducted by 5 students. It includes an abstract, introduction discussing waste water treatment methods for pharmaceutical industries, and sections on literature review, methods of treatment which involve physical, chemical and biological processes, and issues like site selection and environmental impacts. The main goal is to properly design unit operations and select materials to maximize treatment effectiveness and profitability.
This document summarizes a research study that investigated the effect of Fimbristylis ovata, a plant in the sedge family, on vero and MCF-7 cell lines. The study found that a crude methanol extract of F. ovata was able to inhibit the MCF-7 breast cancer cell line with an IC50 value of 73 and the vero cell line with an IC50 value of 280 based on MTT assays. Previous studies had found that F. ovata contains compounds like phenols, saponins, and flavonoids that are known to have anti-cancer effects. The aim of this study was to determine if F. ovata extracts had cytotoxic or anti-cancer potential against these
Targeted drug delivery aims to increase the concentration of drugs in specific tissues while reducing systemic toxicity. It can target drugs to the first order (specific organs), second order (specific cell types), or third order (intracellular sites). Approaches include direct application to affected areas, passive accumulation through leaky vasculature, and active targeting using ligands. Parameters that determine efficacy are the size and blood flow of the target, and number of binding sites. Passive targeting uses physiological or physicochemical factors while active targeting uses carriers functionalized with targeting ligands. Main approaches are retrometabolic systems using drug-carrier complexes and prodrugs that are activated after biotransformation. Examples of targeted delivery systems discussed are magnetic nanoparticles, liposomes
This research paper examines the ability of the drug nelfinavir to overcome multidrug resistance in MCF-7/Dox breast cancer cells. The study finds that multiple exposures to physiologically achievable concentrations of nelfinavir can significantly decrease the doxorubicin IC50 in MCF-7/Dox cells by inhibiting P-glycoprotein expression and function, suppressing AKT signaling pathways, and inducing endoplasmic reticulum stress pathways. In mouse models carrying MCF-7/Dox tumor xenografts, combination treatment with nelfinavir and doxorubicin decreased tumor growth more than either drug alone. The results suggest that nelfinavir can overcome multiple drug resistance
Potential role of bioactive peptides in prevention and treatment of chronic d...NxFxProducerDJ
This review analyzes studies and clinical trials on bioactive peptides and their potential roles in preventing and treating chronic diseases. The review focuses on cardiovascular diseases, immunity, cancer, and other areas. Bioactive peptides from various food sources like fish, milk, meat, and plants have shown effects like lowering blood pressure and lipids in clinical trials. Some peptides also demonstrate anticancer activity in vitro and in vivo as well as immunomodulatory and antimicrobial effects. However, more clinical evidence and standardized extraction procedures are still needed to confirm these effects and enable use of bioactive peptides as preventive or therapeutic treatments.
Background: Nowadays, hybrid drugs have gained a significant role in the treatment of different
health problems. Most of the hybrid molecules with different heterocyclic moieties were proved
to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation
of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to
investigate their anticancer activity by molecular docking studies.
Methods: Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates.
Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies
were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative
target for cancer.
Results: All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and
A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values
of <0.1 μM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on
MCF-7 and A-549 with GI50 values of 0.12 μM and 0.19 μM respectively. Compound 9g showed better
anticancer activity on A-549 cancer cell line with GI50 value of 0.34 μM.
Conclusion: The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard
drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present
docking investigation proved that having benzoxazole of compound 9c at benzofuran of reference
compound N-acetyl pyrazoline derivative might be valid for contributing to anti-cancer activity.
Monoclonal antibodies generated against specific antigens can selectively deliver cytotoxic drugs to cancer cells when conjugated, minimizing damage to normal cells. This allows targeted drug delivery for more effective cancer chemotherapy. The objective of drug targeting is to use a carrier system like monoclonal antibodies to deliver drugs specifically to the site of action. Monoclonal antibodies show promise as drug carriers due to their high specificity for antigens on targeted cells.
HIV enters latency by interrupting viral gene transcription or through epigenetic modification. Tat is a key viral transactivator that regulates HIV transcription through interaction with cofactors like P-TEFb, but does not work alone. New therapies aim to induce viral reactivation from latency ("shock") combined with antiretroviral treatment ("kill") to potentially cure HIV, but challenges remain around drug resistance and side effects of treatment. Research on the Tat-P-TEFb interaction offers hope for developing drugs that induce reactivation by altering P-TEFb levels or activity.
This document discusses drug delivery systems and their applications in modern therapeutics. It begins by defining therapeutics as any measures taken to treat disease. It then contrasts conventional treatment approaches using natural sources to modern approaches using advanced technologies and novel drug formulations. A key problem is delivering drugs to their site of action. The document defines a drug delivery system as a formulation, technology, or system for transporting a drug in the body to safely achieve the desired therapeutic effects at the target site. Drug delivery systems can use drug carriers and be engineered using biotechnology. They provide benefits like decreasing dosing frequency and reducing side effects. In conclusion, drug delivery systems are a modern therapeutic approach that can improve drug potency and safety by controlling drug
This document discusses toxicity testing of chemicals in marine environments. It defines aquatic toxicity, degradability, and bioaccumulation as key properties to assess the potential hazards of chemicals. The goal of toxicity tests is to determine the concentration of a chemical that causes unacceptable negative effects. Toxicity data from species in three trophic levels (algae, invertebrates, fish) is used to calculate the predicted no-effect concentration (PNEC). The document outlines how to determine toxicity through dose-response relationships and endpoints like median lethal concentrations and no observed effect concentrations.
Environmental Risk Assessment for Pharmaceutical DrugsCovance
Understanding the Evaluation and Implications of Findings to the Regulatory Review of Human Medicines in the Environment. Pharmaceutical drugs are intended for the treatment of human disease, therefore the risk of their environmental exposure in clinical use needs to be evaluated. Environmental risk assessment (ERA) is part of the requirements when applying for marketing approval in many geographic regions throughout the world.
To accomplish a desired systemic effect, drug molecules must reach the systemic circulation after extravascular administration. The percent of the taken dose that reaches intact to the systemic circulation is called “bioavailability, BA”. Absolute Bioavailability compares the BA of the active drug in systemic circulation following non-intravenous administration
This document summarizes recent advances in immunotherapy for solid tumors. It discusses how immunotherapy has established itself as an effective treatment strategy, building on William Coley's pioneering work in the late 1800s using bacteria to elicit anti-tumor immune responses. The document outlines several key immunotherapy approaches, including immune checkpoint inhibitors, adoptive cellular therapy, strategies to enhance tumor immunogenicity like radiotherapy and oncolytic viruses, and cancer vaccines. It also discusses how tumor-infiltrating lymphocytes and immunoscore can help predict cancer prognosis and how the immune system interacts with tumors.
The document discusses the process of drug design and development. It begins by defining drugs and their targets at the molecular level. Historically, drugs came from plants and natural products, but now they can be designed rationally through understanding disease processes. The drug design process involves identifying a target, discovering leads, and optimizing candidates through computer modeling and testing before clinical trials. Modern techniques like molecular modeling, virtual screening, and computer-aided design have made drug discovery more efficient, but it remains a long, complex, and expensive process.
Enzymes as drug targets: curated pharmacological information in the 'Guide to...Guide to PHARMACOLOGY
Presented at the British Pharmacological Society Focused meeting in April 2015, this poster summarises the current coverage of our curation of enzyme drug targets and supplements our previous poster covering this target class
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
The document discusses strategies for optimally using limited antimicrobial resources. It notes increasing antimicrobial resistance and a lack of new drug classes. A multidisciplinary team approach including clinical pharmacists can improve outcomes for severe infectious diseases. Clinical pharmacists can help ensure patients receive the most effective drugs while avoiding nephrotoxic options. Their expertise in pharmacology and drug design can also help address resistance and drug failures through modifications to drug molecules or delivery systems. Close monitoring of drug-resistant bacteria is needed to reduce the threat of antimicrobial resistance. Both chance discoveries and targeted research have led to new anti-infective drugs, so a balanced approach that allows creativity could help address current challenges.
The document discusses the challenges of infectious disease treatment including the emergence of drug resistance and limited new drug development. It argues that clinical pharmacists can help optimize antimicrobial use through multidisciplinary teams and applying medicinal chemistry knowledge to drug design and delivery. Serendipity has also played a role in some drug discoveries, though a more systematic approach is needed today given the rise of resistant bacteria.
Annual advances of traditional medicine toxicity in 2018LucyPi1
Abstract There were many researches concerning toxicology of traditional medicine (TM) and active natural products during the past 12 months. This annual toxicology review summarized different analysis methods of toxicology research, common evaluated models, toxic target organs, toxic mechanisms, and popular research issues and herbs in 2018. The emphasis was on hepatorenal toxicity induced by TM through cell apoptosis, metabolic disorder, oxidative stress, inflammatory damage, liver and renal fibrosis and even inducing carcinogenesis. Meanwhile, traditional herbs were listed in this review. Taken together, the herbs mentioned in this paper should be used with caution. Combination of TM, processing drugs, quality control and dose control can be used in the prevention of TM toxicology in the future.
Cheminformatics is an interdisciplinary field that combines chemistry, biology, physics, mathematics, and computer science to manage chemical data and information. It plays a key role in processing the enormous amount of chemical data produced by chemists, maintaining databases, and extracting knowledge from data to model relationships between compound structure and biological activity. Cheminformatics has three major aspects: information acquisition, information management, and information use. It complements bioinformatics by addressing molecular processes like protein structure and function.
This document discusses the concept of endogenous toxicology, which examines pathological conditions from the perspective of toxins produced within the body. It provides several examples:
- Certain neurological diseases may be related to endogenous toxins similar to plant toxins, interacting with receptors evolved in response to environmental toxins.
- Metabolic diseases like diabetes and cardiovascular disease involve the accumulation of endogenous toxic molecules like advanced glycation end products.
- Cancer progression may be influenced by the local microenvironment in organs, with factors like blood flow affecting the likelihood of metastasis to specific sites.
- Many conditions could involve an imbalance or overproduction of endogenous substances acting as toxins in the body. This perspective could provide new approaches to treatment.
This document provides information about a project on waste water treatment in a pharmaceutical factory conducted by 5 students. It includes an abstract, introduction discussing waste water treatment methods for pharmaceutical industries, and sections on literature review, methods of treatment which involve physical, chemical and biological processes, and issues like site selection and environmental impacts. The main goal is to properly design unit operations and select materials to maximize treatment effectiveness and profitability.
This document summarizes a research study that investigated the effect of Fimbristylis ovata, a plant in the sedge family, on vero and MCF-7 cell lines. The study found that a crude methanol extract of F. ovata was able to inhibit the MCF-7 breast cancer cell line with an IC50 value of 73 and the vero cell line with an IC50 value of 280 based on MTT assays. Previous studies had found that F. ovata contains compounds like phenols, saponins, and flavonoids that are known to have anti-cancer effects. The aim of this study was to determine if F. ovata extracts had cytotoxic or anti-cancer potential against these
Targeted drug delivery aims to increase the concentration of drugs in specific tissues while reducing systemic toxicity. It can target drugs to the first order (specific organs), second order (specific cell types), or third order (intracellular sites). Approaches include direct application to affected areas, passive accumulation through leaky vasculature, and active targeting using ligands. Parameters that determine efficacy are the size and blood flow of the target, and number of binding sites. Passive targeting uses physiological or physicochemical factors while active targeting uses carriers functionalized with targeting ligands. Main approaches are retrometabolic systems using drug-carrier complexes and prodrugs that are activated after biotransformation. Examples of targeted delivery systems discussed are magnetic nanoparticles, liposomes
This research paper examines the ability of the drug nelfinavir to overcome multidrug resistance in MCF-7/Dox breast cancer cells. The study finds that multiple exposures to physiologically achievable concentrations of nelfinavir can significantly decrease the doxorubicin IC50 in MCF-7/Dox cells by inhibiting P-glycoprotein expression and function, suppressing AKT signaling pathways, and inducing endoplasmic reticulum stress pathways. In mouse models carrying MCF-7/Dox tumor xenografts, combination treatment with nelfinavir and doxorubicin decreased tumor growth more than either drug alone. The results suggest that nelfinavir can overcome multiple drug resistance
Potential role of bioactive peptides in prevention and treatment of chronic d...NxFxProducerDJ
This review analyzes studies and clinical trials on bioactive peptides and their potential roles in preventing and treating chronic diseases. The review focuses on cardiovascular diseases, immunity, cancer, and other areas. Bioactive peptides from various food sources like fish, milk, meat, and plants have shown effects like lowering blood pressure and lipids in clinical trials. Some peptides also demonstrate anticancer activity in vitro and in vivo as well as immunomodulatory and antimicrobial effects. However, more clinical evidence and standardized extraction procedures are still needed to confirm these effects and enable use of bioactive peptides as preventive or therapeutic treatments.
Background: Nowadays, hybrid drugs have gained a significant role in the treatment of different
health problems. Most of the hybrid molecules with different heterocyclic moieties were proved
to be potent anti-tumor agents in cancer chemotherapy. Hence, the present study is aimed at the evaluation
of in vitro anticancer activity of novel hybrid molecules (pyrazolyl benzoxazole conjugates) and to
investigate their anticancer activity by molecular docking studies.
Methods: Designed, synthesized and characterized the novel pyrazolyl benzoxazole conjugates.
Anticancer activity of these compounds was determined by SRB assay. Then molecular docking studies
were carried out against proto-oncogene tyrosine-protein kinase (ATP-Src, PDB: 2BDF), a putative
target for cancer.
Results: All the synthesized compound derivatives were evaluated against MCF-7, KB, Hop62 and
A549 cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activities with GI50 values
of <0.1 μM against MCF-7 and A549 cell lines. Compound 9e exhibited good antitumor activity on
MCF-7 and A-549 with GI50 values of 0.12 μM and 0.19 μM respectively. Compound 9g showed better
anticancer activity on A-549 cancer cell line with GI50 value of 0.34 μM.
Conclusion: The two-hybrid molecules 9b and 9c are found to be comparably potent with the standard
drug doxorubicin and may act as drug lead compounds in medicinal chemistry aspect. The present
docking investigation proved that having benzoxazole of compound 9c at benzofuran of reference
compound N-acetyl pyrazoline derivative might be valid for contributing to anti-cancer activity.
Monoclonal antibodies generated against specific antigens can selectively deliver cytotoxic drugs to cancer cells when conjugated, minimizing damage to normal cells. This allows targeted drug delivery for more effective cancer chemotherapy. The objective of drug targeting is to use a carrier system like monoclonal antibodies to deliver drugs specifically to the site of action. Monoclonal antibodies show promise as drug carriers due to their high specificity for antigens on targeted cells.
HIV enters latency by interrupting viral gene transcription or through epigenetic modification. Tat is a key viral transactivator that regulates HIV transcription through interaction with cofactors like P-TEFb, but does not work alone. New therapies aim to induce viral reactivation from latency ("shock") combined with antiretroviral treatment ("kill") to potentially cure HIV, but challenges remain around drug resistance and side effects of treatment. Research on the Tat-P-TEFb interaction offers hope for developing drugs that induce reactivation by altering P-TEFb levels or activity.
This document discusses drug delivery systems and their applications in modern therapeutics. It begins by defining therapeutics as any measures taken to treat disease. It then contrasts conventional treatment approaches using natural sources to modern approaches using advanced technologies and novel drug formulations. A key problem is delivering drugs to their site of action. The document defines a drug delivery system as a formulation, technology, or system for transporting a drug in the body to safely achieve the desired therapeutic effects at the target site. Drug delivery systems can use drug carriers and be engineered using biotechnology. They provide benefits like decreasing dosing frequency and reducing side effects. In conclusion, drug delivery systems are a modern therapeutic approach that can improve drug potency and safety by controlling drug
This document discusses toxicity testing of chemicals in marine environments. It defines aquatic toxicity, degradability, and bioaccumulation as key properties to assess the potential hazards of chemicals. The goal of toxicity tests is to determine the concentration of a chemical that causes unacceptable negative effects. Toxicity data from species in three trophic levels (algae, invertebrates, fish) is used to calculate the predicted no-effect concentration (PNEC). The document outlines how to determine toxicity through dose-response relationships and endpoints like median lethal concentrations and no observed effect concentrations.
Environmental Risk Assessment for Pharmaceutical DrugsCovance
Understanding the Evaluation and Implications of Findings to the Regulatory Review of Human Medicines in the Environment. Pharmaceutical drugs are intended for the treatment of human disease, therefore the risk of their environmental exposure in clinical use needs to be evaluated. Environmental risk assessment (ERA) is part of the requirements when applying for marketing approval in many geographic regions throughout the world.
To accomplish a desired systemic effect, drug molecules must reach the systemic circulation after extravascular administration. The percent of the taken dose that reaches intact to the systemic circulation is called “bioavailability, BA”. Absolute Bioavailability compares the BA of the active drug in systemic circulation following non-intravenous administration
This document summarizes recent advances in immunotherapy for solid tumors. It discusses how immunotherapy has established itself as an effective treatment strategy, building on William Coley's pioneering work in the late 1800s using bacteria to elicit anti-tumor immune responses. The document outlines several key immunotherapy approaches, including immune checkpoint inhibitors, adoptive cellular therapy, strategies to enhance tumor immunogenicity like radiotherapy and oncolytic viruses, and cancer vaccines. It also discusses how tumor-infiltrating lymphocytes and immunoscore can help predict cancer prognosis and how the immune system interacts with tumors.
The document discusses the process of drug design and development. It begins by defining drugs and their targets at the molecular level. Historically, drugs came from plants and natural products, but now they can be designed rationally through understanding disease processes. The drug design process involves identifying a target, discovering leads, and optimizing candidates through computer modeling and testing before clinical trials. Modern techniques like molecular modeling, virtual screening, and computer-aided design have made drug discovery more efficient, but it remains a long, complex, and expensive process.
Enzymes as drug targets: curated pharmacological information in the 'Guide to...Guide to PHARMACOLOGY
Presented at the British Pharmacological Society Focused meeting in April 2015, this poster summarises the current coverage of our curation of enzyme drug targets and supplements our previous poster covering this target class
Pharmacogenomics is the study of how genes affect individual responses to drugs. It combines pharmacology and genomics to develop safe and effective personalized medications and dosages based on a person's genetic makeup. The goal is to improve treatment outcomes by predicting drug effectiveness and reducing adverse reactions. Challenges include implementing genetic tests in clinical practice and addressing cost, ethical and legal issues. Future applications include developing tailored drugs for many diseases and faster, more targeted clinical trials through biomarkers.
The document discusses strategies for optimally using limited antimicrobial resources. It notes increasing antimicrobial resistance and a lack of new drug classes. A multidisciplinary team approach including clinical pharmacists can improve outcomes for severe infectious diseases. Clinical pharmacists can help ensure patients receive the most effective drugs while avoiding nephrotoxic options. Their expertise in pharmacology and drug design can also help address resistance and drug failures through modifications to drug molecules or delivery systems. Close monitoring of drug-resistant bacteria is needed to reduce the threat of antimicrobial resistance. Both chance discoveries and targeted research have led to new anti-infective drugs, so a balanced approach that allows creativity could help address current challenges.
The document discusses the challenges of infectious disease treatment including the emergence of drug resistance and limited new drug development. It argues that clinical pharmacists can help optimize antimicrobial use through multidisciplinary teams and applying medicinal chemistry knowledge to drug design and delivery. Serendipity has also played a role in some drug discoveries, though a more systematic approach is needed today given the rise of resistant bacteria.
INNOVATIVE MEDICINES, TECHNOLOGIES AND APPROACHES FOR IMPROVING PATIENTS' HE...Jing Zang
Despite remarkable scientific and technological achievements during the 20th century, the 21st century has already witnessed additional new and profound changes in all areas of medical science and research, including innovations and discoveries in biology, cellular biology, genomics and proteomics, pharmaceuticals, medical devices, and information technology. This review is an up-date on some of the existing therapies, drug delivery technologies, and approaches that aimed to improve patients’ health care and quality of their life.
International Organization of Scientific Research (IOSR)iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
In silico Drug Design: Prospective for Drug Lead Discoveryinventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Chemical Compounds used in Medicines and their Impact on Humanijtsrd
Chemicals are used to create medicines. Chemical analysis and the synthesis of novel chemicals are used to create new medications. This topic is so wide that it has spawned a new branch of chemistry known as -‘Medicinal Chemistry’ of -‘Chemicals in Medicines’. Medicinal chemistry is a branch of chemistry concerned with the design, analysis, development, and synthesis of drugs as medicine. Medicines are chemical compounds that help living creatures in the treatment of diseases or the relief of suffering. This discipline necessitates knowledge in synthetic organic chemistry, pharmacology, and biological sciences. Medicines include numerous compounds. Medicines have an important role in the treatment and prevention of disease in both humans and animals. But it is because of the very nature of medicines that they may also have unintended effects on animals and microorganisms in the environment. Although the side effects on human and animal health are usually investigated in thorough safety and toxicology studies, the potential environmental impacts of the manufacture and use of medicines are less well understood and have only recently become a topic of research interest. More than 10 million women in the USA alone use oral contraceptives, which eventually find their way into the environment. A wide range of human medicines, including antibiotics, statins or cytotoxins used in cancer treatment, are produced and used, some in the range of thousands of tons per year. It is hard to obtain information on the amount of human medicines used, but recent data from Canada indicates that high use drugs include acetominophen, acetylsalicylic acid, ibuprofen, naproxen and carbamazepine. Dr. Ashutosh Tripathi | Neeraj Pandey "Chemical Compounds used in Medicines and their Impact on Human" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-6 , October 2022, URL: https://www.ijtsrd.com/papers/ijtsrd52116.pdf Paper URL: https://www.ijtsrd.com/chemistry/other/52116/chemical-compounds-used-in-medicines-and-their-impact-on-human/dr-ashutosh-tripathi
This document describes the design, synthesis, and in vitro anticancer evaluation of novel pyrazolyl benzoxazole conjugates. The conjugates were synthesized through a multi-step reaction involving the condensation of 3-phenyl-1H-pyrazole-5-carboxylic acid with substituted 2-aminophenols. The conjugates were evaluated for anticancer activity against four human cancer cell lines. Compounds 9b and 9c exhibited excellent anticancer activity comparable to doxorubicin with GI50 values below 0.1 μM. Molecular docking studies revealed compounds 9b and 9c bound strongly to the ATP binding site of proto-oncogene tyrosine-protein kinase, a putative cancer target
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology.
A study on prescription pattern and rational use of statins in tertiary care ...SriramNagarajan16
Objectives
Our objectives are to evaluate prescription pattern and rational use of statins in a tertiary care corporate hospital.
Methodology
It was a prospective observational study conducted for a period of 6 months and included various departments of 300
bedded multi specialty tertiary care corporate hospital. A total of 200 patients were included and the study criteria
was inpatients and induvial more than 18 years of either gender who are prescribed with HMG-CoA reductase
inhibitors.
Results
In the present study 200 patients belonged to the age group of above 18 years, out of which about 65% were male
and 35% were female. Atorvastatin (67%) was prescribed mostly and Rosuvastatin (29.5%) was also used.
Conclusion
It is finally concluded that Rational and prophylactic use of statins can reduce further complications of Diabetes
Mellitus (DM) and cardiac events.
Statins treatment is favourable in long term treatment of diseases, it is most effectively used in treatment of serious
disease conditions which has shown its immense therapeutic role in treatment
Nanoparticle Based Targeting Approaches for Lung Cancer: A Mini ReviewAI Publications
Every year more than 10 million people are diagnosed with cancer and more than 6 million deaths – around 12% of deaths worldwide. The objective of cancer treatment still is to cure the patients if possible or prolong their life and improve their quality of life by surgical removal of the cancerous tissue, radiation therapy, biotherapy, chemotherapy, bone marrow transplant or a combination of some of these available treatments. This review aims to explore the various approaches using nanotechnology and surface decoration with ligands capable to target lung cancers.
This document summarizes several key molecular targets in cancer therapy and discusses how traditional Ayurvedic medicine may provide leads in developing treatments by modulating these targets. It describes major targets like the NF-κB, AP-1, and JAK-STAT pathways that are involved in processes like inflammation, proliferation, apoptosis, and drug resistance. The document then discusses how phytochemicals from plants used in Ayurveda have been shown to suppress many of these same targets and molecular pathways. It suggests Ayurvedic medicine could provide insights on new therapeutic agents if rediscovered in light of modern knowledge of cancer biology.
Linde Gas whitepaper 'Drug discovery advances inextricably linked to specialt...Linde Gas Benelux
The development and commercialisation of new medical drugs is a complex and costly process, but increasing pressure is being placed on drug companies to accelerate the timeline from discovery of new drugs, through to clinical trials and then to their release onto the market. The pharmaceutical industry continues to demand ever more advanced products aimed at improving health and the quality of modern-day life.
Research and development take place in pharmaceutical laboratories using analytical instruments such as gas chromatographs with multiple detectors, liquid chromatographs coupled with mass spectrometers (LC-MS), ultraviolet/visible (UV/VIS) spectrometers and nuclear magnetic resonance (NMR) spectrometers. These significantly accelerate research and development cycles, ultimately bringing beneficial drugs onto the market faster than ever before. The effective operation of these instruments depends on the use of the appropriate gases or gas mixtures.
Ultrasound Technology as a Novel Treatment Strategy in Pancreatic Cancer_Crim...CrimsonpublishersCancer
Adenocarcinoma of the pancreas (PDAC) accounts for 2.4% of all cancers diagnosed and is the fourth leading cause of cancer death, with almost equal rates of incidence and mortality [1]. By 2030, pancreatic cancer is projected to be the second leading cause of cancer-related death [2], surpassing breast, prostate and colorectal cancer. The overall survival at 5 years of around 7.2% as the majority of patients present with advanced disease at diagnosis. Patients with localized disease are treated with surgery, with or without neoadjuvant chemotherapy/ radiotherapy, followed by adjuvant chemotherapy. The majority (around 80%) of patients are treated only with chemotherapy as they have an advanced disease. Patients are treated in the first line with gemcitabine-abraxane or Folfirinox and with Naliri plus 5FU in the second line. There have been few clinical advances in PDAC treatment over the last 20 years and chemotherapy is the only treatment option available for the majority of patients. These tumours are also resistant to many targeted therapies such as anti-EGFR therapy like cetuximab [3] due to the presence of a KRAS mutation in the majority of primary tumors. Personalized medicine strategies have not yet been established in pancreatic cancer as in other more common tumour types. Thus, novel anti-tumour strategies are an important clinical need in order to improve survival rates.
Relative Properties and Relative Potency of Various Hydrazide Compounds That ...IOSRJPBS
This document summarizes the molecular properties and relative potency of various hydrazide compounds that inhibit the growth of Mycobacterium tuberculosis. It describes the molecular structures of nine hydrazide compounds tested, including isoniazid. It analyzes the compounds' molecular properties like Log P, polar surface area, molecular weight, and number of atoms. All compounds showed zero violations of the "Rule of 5" indicating favorable drug-likeness. Minimum inhibitory concentrations ranged from 16.7 to 65.9 ug/mL. Estimated brain penetration (Log BB) was calculated and no outliers were found. Overall, the compounds exhibited variation in properties but remained favorable for inhibiting tuberculosis growth.
Ligand and structure based drug design against antimicrobial resistance induc...Mohit Kumar
Helicobacter pylori is a gram-negative, microaerophilic bacterium found usually in the stomach of a person with chronic gastritis and gastric ulcers. More than 50% of the world’s population harbor H. pylori in their upper gastrointestinal tract. About 85% of people infected with H. pylori never experience symptoms or complications. Individuals with chronic gastritis and infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers, MALT lymphoma, the pathogenesis of gastric cancer and several extra-gastric diseases. No vaccines are developed yet and the bacterial antibiotic resistance has been a growing concern. Helicobacter pylori produce virulence and antibiotic resistance through quorum sensing mechanisms by generating AI-2. Inhibition of quorum sensing would be a novel approach for the effective treatment of antibiotic-resistant strains of H. pylori. Chemical nature of AI-2 is furanosyl borate diester which is generated from 4,5-dihydroxy 2,3-pentanedione (DPD). But there are no synthetic congeners of AI-2 and DPD compounds tested against H. pylori till date. Therefore, it is the aim of the present study to design some potent AI-2 and DPD compounds under the framework of pharmacophore modeling.
Neglected and rare diseases traditionally have not been the focus of large pharmaceutical company research as biotech and academia have primarily been involved in drug discovery efforts for such diseases. This area certainly represents a new opportunity as the pharmaceutical industry investigates new markets. One approach to speed up drug discovery is to examine new uses for existing approved drugs; this is termed drug repositioning or drug repurposing and has become increasingly popular in recent years. Analysis of the literature reveals that using high-throughput screening there have been many examples of FDA approved drugs found to be active against additional targets that can be used to therapeutic advantage for repositioning for other diseases. To date there are far fewer such examples where in silico approaches have allowed for the derivation of new uses. It is suggested that with current technologies and databases of chemical compounds (drugs) and related data, as well as close integration with in vitro screening data, improved opportunities for drug repurposing will emerge. In this publication a review of the literature will highlight several proof of principle examples from areas such as finding new inhibitors for drug transporters with 3D pharmacophores and uncovering molecules active against Mycobacterium tuberculosis (Mtb) using Bayesian models of compound libraries. Research into neglected or rare/orphan diseases can likely benefit from in silico drug repositioning approaches and accelerate drug discovery for these diseases.
The document discusses the role of clinical pharmacists in medical teams treating severe and critical patients. It argues that including clinical pharmacists can reduce mortality rates by adding pharmaceutical knowledge and expertise to evaluate drug efficacy and make treatment decisions. The main focus of clinical pharmacists should be on the most critical patients, as their contributions can save lives. Their presence helps optimize pharmacological strategies and outcomes through competencies in areas like pharmacokinetics, drug design, and preventing antimicrobial resistance.
A radiology report serves as an intermediary between a radiologist and referring clinician for suggesting
appropriate treatment to the patients, aimed at better healthcare management. It is essentially a tool
that assists radiologists in conveying their input to the patients and clinicians regarding positive or negative findings on a case. The objective of this paper is to discuss and propose Radiology Information & Reporting System (RIRS), highlight challenges governing its implementation and suggest way forwards
towards its effective implementation across the public sector tertiary care institutions of Pakistan. In the end, it is concluded that the proposed RIRS would potentially offer enormous benefits in terms of cost
savings, reporting accuracy, faster processing and operational efficiency as opposed to the conventionally available manual radiology reporting procedures and systems.
This document provides an overview of targeted chemotherapy and reviews recent developments. It discusses how targeted therapies like monoclonal antibodies and small molecule inhibitors precisely target molecular changes in cancer cells, potentially causing fewer side effects than traditional chemotherapy. The document outlines several FDA-approved targeted drugs and their indications. It also discusses considerations for targeted therapy like evaluating effectiveness through biomarkers, increased costs compared to chemotherapy, and challenges in determining optimal dosing. Future areas of research discussed include personalized treatment based on a patient's molecular profile and defining dose-response relationships through randomized trials.
Nanotechnology in Targeted Drug Delivery.pdfAzeem Muhammed
This document discusses nanotechnology for targeted drug delivery and therapeutics. It describes how nanocarriers such as liposomes, polymeric nanoparticles, micelles, dendrimers, and hydrogels can be used as drug delivery platforms. These nanocarriers protect drugs, allow for controlled release, and can be modified for targeted delivery through conjugation of ligands. Many nanocarrier drug delivery systems are currently in clinical trials for applications such as cancer therapy and treatment of other diseases.
Similar to Synthesis and Antitumor Activity Evaluation of 2-Aminothiazoles Appended 5-methylisoxazoline and Pyridine-piperazine Hybrid Molecules (20)
Electrochemical study of anatase TiO2 in aqueous sodium-ion electrolytesRatnakaram Venkata Nadh
In this paper, a basic electro-analytical study on the behavior of anatase TiO2 in aqueous NaOH has been presented using cyclic voltammetry technique (CV). The study has explored the possibility of using TiO2 as anode material for ARSBs in presence of 5 M NaOH aqueous electrolyte. CV profiles show that anatase TiO2 exhibits reversible sodium ion insertion/de-insertion reactions. CV studies of TiO2 anode in aqueous sodium electrolytes at different scan rate shows that the Na+ ion insertion reaction at the electrode is diffusion controlled with a resistive behavior. Proton insertion from aqueous sodium electrolytes into TiO2 cannot be ruled out. To confirm the ion inserted and de-inserted, CV studies are done at different concentration of NaOH and it is found that at lower concentrations of NaOH, proton insertion process competes with Na+ ion insertion process and as the concentration increases, the Na+ ion insertion process becomes the predominant electrode reaction making it suitable anode materials for aqueous sodium batteries in 5 M NaOH.
Validated HPLC Method for Assay and Content Uniformity Testing of Roflumilast...Ratnakaram Venkata Nadh
Roflumilast is a selective enzyme inhibitor of phosphodiesterase-4. This drug is recommended for treatment of patients suffering from
chronic-obstructive-pulmonary-disease with chronic-bronchitis. Roflumilast is not official in pharmacopoeia and the reported methods
are having high chromatographic run times. A short run time HPLC method was developed for assay and content uniformity testing to
determine the roflumilast in blend and tablets. The mobile phase consists of 10 mM sodium dihydrogen phosphate monohydrate buffer
and acetonitrile in the ratio of 45:55 v/v. The HPLC method was developed using accucore-C18 150 × 4.6 mm, 4 μm column with a flow
rate of 1.0 mL min-1, 215 nm wavelength and 10 μL injection volume with run time of 5 min. The method linearity was proved between
5.02-40.17 μg mL-1 and obtained correlation-coefficient value is 1.0000. The mean recovery of roflumilast was 100.6%. The stability
indicating nature was established and performed the validation by considering ICH Q2 (R1) recommendations.
Substrate Inhibition in Ruthenium(III) Catalyzed Oxidation of Propane-1,3-dio...Ratnakaram Venkata Nadh
- Ruthenium(III) catalyzed oxidation of propane-1,3-diol by potassium periodate was studied in aqueous perchloric acid medium.
- The reaction was found to be first order in oxidant and catalyst concentrations, and inverse fractional order in acid concentration. Substrate inhibition was also observed with increasing substrate concentration.
- Various reaction conditions like temperature, addition of salts, and acetic acid-water solvent composition were varied to determine their effects. Based on the kinetic data, a plausible reaction mechanism was proposed.
Ruthenium(III) Catalyzed Oxidation of Sugar Alcohols by Dichloroisocyanuric A...Ratnakaram Venkata Nadh
Kinetics of ruthenium(III) catalyzed oxidation of biologically important sugar alcohols (myo-inositol,
D-sorbitol, and D-mannitol) by dichloroisocyanuric acid was carried out in aqueous acetic acid—perchloric
medium. The reactions were found to be first order in case of oxidant and ruthenium(III). Zero order
was observed with the concentrations of sorbitol and mannitol whereas, a positive fractional order was found
in the case of inositol concentration. An inverse fractional order was observed with perchloric acid in oxidation
of three substrates. Arrhenius parameters were calculated and a plausible mechanism was proposed
Shift of Reaction Pathway by Added Chloride Ions in the Oxidation of Aromatic...Ratnakaram Venkata Nadh
Role of added chloride ions on the shift of reaction pathway of oxidation of aromatic ketones (acetophenone,
desoxybenzoin) by dichloroisocyanuric acid (DCICA) was studied in aqueous acetic acid—perchloric
acid medium. Participation of enolic and protonated forms of ketones in the rate determining steps is
manifested from zero and first orders with respect to the oxidant in absence and presence of added chloride
ions, respectively. Positive and negative effects of acid and dielectric constant on the reaction rate were
observed. The observations deduce plausible mechanisms involving (i) rate-determining formation of enol
from the conjugate acid of the ketone (SH+) in the absence of added chloride ions and (ii) rapid formation of
molecular chlorine species from HOCl (hydrolytic species of DCICA) in the presence of added chloride ions,
which then interacts with SH+ in a rate-determining step prior to the rapid steps of product formation. The
order of Arrhenius parameters substantiate the proposed plausible mechanisms based on order of reactants
both in presence and absence of added chloride ions.
Kinetics of Ruthenium(III) Catalyzed and Uncatalyzed Oxidation of Monoethanol...Ratnakaram Venkata Nadh
Kinetics of uncatalyzed and ruthenium(III) catalyzed oxidation of monoethanolamine by N-bromosuccinimide
(NBS) has been studied in an aqueous acetic acid medium in the presence of sodium acetate
and perchloric acid, respectively. In the uncatalyzed oxidation the kinetic orders are: the first order in NBS,
a fractional order in the substrate. The rate of the reaction increased with an increase in the sodium acetate
concentration and decreased with an increase in the perchloric acid concentration. This indicates that free
amine molecules are the reactive species. Addition of halide ions results in a decrease in the kinetic rate,
which is noteworthy. Both in absence and presence of a catalyst, a decrease in the dielectric constant of the
medium decreases the kinetic rate pointing out that these are dipole—dipole reactions. A relatively higher
oxidation state of ruthenium i.e., Ru(V) was found to be the active species in Ru(III) catalyzed reactions. A
suitable mechanism consistent with the observations has been proposed and a rate law has been derived to
explain the kinetic orders.
A novel reversed-phase liquid chromatographic method for the simultaneous det...Ratnakaram Venkata Nadh
In the present study 12 impurities of bisoprolol fumarate (BISO) and hydrochlorothiazide (HCTZ) were
separated simultaneously in a single HPLC method. Out of these 12 impurities, five are potential
degradants, which are validated as per The International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use (ICH) guidelines. As the two active drug substances
BISO and HCTZ have different solubilities and polarities, the most critical parameters in resolving the
components from each other are pH, temperature, and solvents. The method is precise (RSD < 1.0%),
accurate, linear (r2 > 0.999), robust, and stability indicating in the range of limit of quantification (LOQ)
to 150%. The HPLC method is then migrated to ultra-performance liquid chromatography (UPLC) to
further reduce the run time and solvent consumption, and increase the sample throughput
The emergence of multidrug-resistant TB (MDR-TB) against first-line drugs and extensively drug resistant TB (XDRTB)
due to misuse of second-line anti tubercular drugs (ATDs) is a further concern. Recommended treatment involves
long term and multiple drug therapy with severe side effects. Due to this concern nanoparticle-based systems
have significant potential for treatment and prevention of tuberculosis (TB) to overcome the need to administer
ATDs at high and frequent doses, would assist in improving patient compliance and circumvent hepatotoxic ity
and/or nephrotoxicity/ocular toxicity/ototoxicity associated with the prevalent first-line chemotherapy.
Nanostructured delivery systems constitute a wide range of systems varying from liposomes, micelles, micro- and
nanoemulsions, to polymeric nanoparticles (PNPs ) and solid lipid nanoparticles (SLNs). Pulmonary administration
of inhaled nanoparticles in the form of dry powder inhalers offer particular advantages for pulmonary administration
of anti tubercular drugs (ATDs). Present review comprehensively about different approaches of nanobased
drug delivery, devises and techniques for pulmonary delivery of nanoparticle encapsulated ATD.
Kinetic, isotherm and thermodynamics investigation on adsorption of divalent ...Ratnakaram Venkata Nadh
Three novel and distinct agricultural waste materials, viz., Casuarinas fruit powder (CFP), sorghum stem powder
(SSP) and banana stem powder (BSP) were used as low cost adsorbents for the removal of toxic copper(II) from
aqueous solutions. Acid treated adsorbents were characterized by SEM, EDX and FTIR. Different factors effecting
adsorption capacity were analyzed and the effi ciency order was BSP>SSP>CFP. Based on the extent of compatibility
to Freundlich/Langmuir/D-R/Temkin adsorption isotherm and different models (pseudo-fi rst and second order,
Boyd, Weber’s and Elovich), chemisorption primarily involved in the case of CFP and SSP, whereas, simultaneous
occurrence of chemisorption and physisorption was proposed in the case of BSP. Based on the observations, it was
proposed that three kinetic stages involve in adsorption process viz., diffusion of sorbate to sorbent, intra particle
diffusion and then establishment of equilibrium. These adsorbents have promising role towards removal of Cu(II)
from industrial wastewater to contribute environmental protection.
Kinetic, thermodynamic and equilibrium studies on removal of hexavalent chrom...Ratnakaram Venkata Nadh
Removal of Cr(VI) by biosorption on two agro waste materials, casuarinas fruit powder (CFP) and sorghum
stem powder (SSP), has been investigated. The prepared adsorbent materials were characterized by SEM, EDX,
FTIR and BET. These biomaterials effectively removed Cr(VI) with a maximum removal of 93.35% and 63.75% using
15 gL−1 and 5 gL−1 of CFP and SSP, respectively, at 60 oC with 20mgL−1 initial Cr(VI) concentration in solution. In both
cases of adsorbents, kinetic data of adsorption fitted well in pseudo-second-order in terms of correlation coefficient
(R2). This helps in proposing the process of adsorption as chemical coordination, which is correlated with the thermodynamic
study results conducted at different values of temperature. Langmuir, Freundlich and D-R models were evaluated
for description of metal sorption isotherms. Values of coefficients of intra-particle diffusion and mass transfer have
also been determined at different values of temperature.
Novel coumarin isoxazoline derivatives: Synthesis and study of antibacterial ...Ratnakaram Venkata Nadh
A highly efficient and mild protocol for the syntheses of ethyl-3-
[7-benzyloxy-4-methyl-2-oxo-2H-8-chromenyl]-5-aryl-4,5-dihydro-4-
isoxazole carboxylates and ethyl-3-[7-benzyloxy-3-chloro-4-methyl-2-
oxo-2H-8-chromenyl]-5-aryl-4,5-dihydro-4-isoxazole carboxylates in
good yields via [3 þ 2] cycloaddition of in situ–generated nitrile
oxides from 7-benzyloxy-4-methyl-coumarin hydroxymoylchlorides
and 7-benzyloxy-3-chloro-4-methyl-coumarin hydroxymoylchlorides
respectively with ethyl-3-aryl prop-2-enoate has been developed.
The new compounds are screened for antibacterial activity.
Ultra performance liquid chromatographic method for simultaneous quantificati...Ratnakaram Venkata Nadh
Plerixafor (PLX) injections are administered to patients with cancers of lymphocytes
(non-Hodgkin’s lymphoma) and plasma cells (multiple myeloma). The main
objective of the current study was to develop a short reverse phase chromatographic
method for the simultaneous quantification of PLX and its impurities, in an injection
formulation, to reduce the time required for these quality tests. Furthermore, the
present work describes the role of nonalkyl branched nonquaternary ion pair reagent
in improving the peak shape and reducing column equilibration time. The separation
of PLX and its related substances is pH dependent (optimum pH = 2.50) and was
achieved on an octadecylsilyl (C18) column. The method was validated for its intended
purpose in accordance with the current regulatory guidelines for validation. The
proposed method can be applied for quality control, release, and stability analyses of
active pharmaceutical ingredient, PLX, as well as finished products, PLX injections
Caralluma lasiantha: A review on it’s vital role in Indian Traditional MedicineRatnakaram Venkata Nadh
Caralluma is a genus used as traditional medicine. Caralluma lasiantha is medicinally important due
to existence of pregnane glycosides, which may possess various biological activities. This article thoroughly
reviewed about the usage of C. lasiantha in traditional medicinal system, phytochemicals present in it, profile
identification studies, anti-hyperglycemic effect, antibacterial, antifungal, cytotoxic and antioxidant activities
Phytochemical Investigation of Caralluma lasiantha: Isolation of Stigmasterol...Ratnakaram Venkata Nadh
This document summarizes the isolation and identification of stigmasterol from Caralluma lasiantha. Stigmasterol was isolated using a sequence of steps including saponification, fractional crystallization, and column chromatography. Structural identification was confirmed through spectral data including IR, 1H NMR, 13C NMR, and mass spectrometry, as well as by comparing data to literature values. Stigmasterol is a phytosterol that was isolated for the first time from this plant species.
Phytochemical Screening of Caralluma lasiantha Isolation of C21 Pregnane SteroidRatnakaram Venkata Nadh
Phytochemical screening of Caralluma lasiantha was carried out and one C21 pregnane steroid was isolated from chloroform extract. Based on spectroscopic studies (IR, 1H NMR, 13C NMR and ESI-MS) the isolated compound is 3b,14b-dihydroxy-14b-pregn-5-en-20-one which was earlier isolated from other species.
Supercritical fluid (CO2) chromatography for quantitative determination of se...Ratnakaram Venkata Nadh
In the present study, two cancer therapeutic drugs (docetaxel and bortezomib) were separated from their
potential impurities on a chromatographic platform by utilizing CO2 gas (supercritical state) and quantified.
The chromatographic separations were achieved on two short columns BEH-2EP (100mm 3mm, 1.7 mm)
and CHIRALPAK AD-3 (100 mm 4.6 mm, 3 mm) for docetaxel and bortezomib, respectively. The present
work describes the role of organic modifiers in the separation of polar compounds by supercritical fluid
chromatography. The two new methods were fully validated in accordance with the current ICH
(International Council for Harmonization of technical requirements for pharmaceuticals for human use)
guidelines. The stability indicating power of the methods was demonstrated from the stress studies
conducted on the injection formulations of the two compounds. The methods are precise with % RSD of
0.4, linear with the correlation coefficient of r2 $ 0.999 and accurate in the range of 50–150% of the
target assay concentration. The two methods can be equally employed for the assay determination of
docetaxel and bortezomib APIs as well.
Quality-by-design-based development and validation of a stability-indicating ...Ratnakaram Venkata Nadh
A systematic design-of-experiments was performed by applying quality-by-design concepts to determine
design space for rapid quantification of teriflunomide by the ultraperformance liquid chromatography
(UPLC) method in the presence of degradation products. Response surface and central composite
quadratic were used for statistical evaluation of experimental data using a Design-Expert software. The
response variables such as resolution, retention time, and peak tailing were analyzed statistically for the
screening of suitable chromatographic conditions. During this process, various plots such as perturbation,
contour, 3D, and design space were studied. The method was developed through UPLC BEH C18
2.1 � 100 mm, 1.7-μ column, mobile phase comprised of buffer (5 mM K2HPO4 containing 0.1%
triethylamine, pH 6.8), and acetonitrile (40:60 v/v), the flow rate of 0.5 mL min 1 and UV detection at
250 nm. The method was developed with a short run time of 1 min. Forced degradation studies revealed
that the method was stability-indicating, suitable for both assay and in-vitro dissolution of a drug product.
The method was found to be linear in the range of 28–84 μg mL 1, 2.8–22.7 μg mL 1 with a correlation
coefficient of 0.9999 and 1.000 for assay and dissolution, respectively. The recovery values were found in
the range of 100.1–101.7%. The method was validated according to ICH guidelines.
A convenient new and efficient commercial synthetic route for dasatinib (Spry...Ratnakaram Venkata Nadh
A new and efficient synthetic route for dual-Src/Abl kinase inhibitor
dasatinib (Sprycel®), an anticancer drug, is described. This commercially
viable process yields dasatinib monohydrate free of potential impurities
with consistent yield of 68% in route A and 61% in route B with HPLC
purity >99.80% over four stages.
Utilization of agro-waste for removal of toxic hexavalent chromium: surface i...Ratnakaram Venkata Nadh
Abundantly available agricultural waste materials
(banana bunch, sorghum stem and casuarinas fruit) are
processed with negligible cost and are found to be highly
suitable as biosorbents for chromium(VI) removal from
aqueous environment due to high surface area and functional
groups of adsorbents. The equilibrium data have
been analyzed for the adsorbate–adsorbate/adsorbent
interactions and found to be fitted to the data in the order,
Hill–de Boer C Fowler–Guggenheim % Frumkin[Kiselev.
To determine the characteristic parameters for process
design, mass transfer studies have been carried out using
two-parameter isotherm models (Harkins–Jura, Halsey,
Smith, El-Awady and Flory–Huggins) and three-parameter
isotherm models (Redlich–Peterson and Sips) which are
applied to the experimental data. The fitness of the isotherms
describes that both mono- and multilayer adsorptions
occur in the present studied three biosorbents in
preference to the latter. The mechanism of adsorption has
been studied using diffusion kinetic models (viz. liquid film
diffusion, Dunwald–Wagner intra-particle diffusion model
and moving boundary model) and described the possibility
of diffusion in the order of banana bunch–stem powder[
sorghum stem powder[casuarinas fruit powder in
terms of diffusion coefficients. In essence of all the results,
the selected adsorbents can be used as a potential adsorbent
for the removal of Cr(VI) from aqueous solutions.
Evaluation of in vitro antibacterial activity of Caralluma lasiantha for scie...Ratnakaram Venkata Nadh
Caralluma lasiantha is used as a traditional medicine in India to heal body
heat and inflammations. In order to find out a scientific validation for the Indian
traditional knowledge, antibacterial activity of C. lasiantha extracts was studied
against inflammation causing bacteria (viz., Staphylococcus aureus, Escherichia coli,
Streptococcus Sp., Bacillus subtilis, Enterobacter aerogenes, Klebsiella pneumoniae)
along with other Gram-positive and Gram-negative bacteria. Solvents with different
polarity were used for extraction from dry roots and stems. Minimum inhibitory
concentrations (MIC) were also studied. Differential antibacterial activity was
exhibited by extracts and higher inhibition potential against Gram-positive bacteria
was explained. The observed antibacterial activities were correlated with the chemical
structures of phytochemicals present in C. lasiantha. Anti-inflammation activities
are related to C. lasiantha extracts through their antibacterial activities.
10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
DECLARATION OF HELSINKI - History and principlesanaghabharat01
This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
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2. 2 Letters in Organic Chemistry, 2018, Vol. 15, No. 0 Suresh et al.
20]. Cancer is the second leading cause of death in high-
income countries (following cardiovascular diseases) and the
third leading cause of death in low- and middle-income
countries (following cardiovascular diseases and infectious
and parasitic diseases). According to estimates from the In-
ternational Agency for Research on Cancer (IARC), there
were 14.1 million new cancer cases in 2012 worldwide, of
which 8 million occurred in economically developing coun-
tries, which contain about 82% of the world’s population.
These estimates do not include non-melanoma skin cancers,
which are not tracked in cancer registries. The corresponding
estimates for total cancer deaths in 2012 were 8.2 million
(about 22,000 cancer deaths a day) – 2.9 million in economi-
cally developed countries, and 5.3 million in economically
developing countries. However, the estimated future cancer
burden will probably be considerably larger due to the adop-
tion of lifestyles that are known to increase cancer risk, such
as smoking, poor diet, physical inactivity, and fewer preg-
nancies, in economically developing countries. A tour-de-
force development in anticancer research results vast number
of anticancer drugs. Based on the mode of action these anti-
cancer drugs are broadly categorized into three main groups
[21].
a) Genotoxic agents.
b) Antimetabolites.
c) Mitotic spindle inhibitors.
In view of the seriousness of the dreadful disease and
improved drug resistance among the cancer cells, there is a
continuous need for the development of new anticancer
drugs [21].
“Thiazole, a nitrogen-sulfur containing” heterocycle is
widely used as an important synthetic intermediate for the
preparation of large number of pharmaceutical drug prod-
ucts. A number of drugs including Famotidine, Cefdinir and
Meloxcam are widely distributed in the market which con-
tains 2-aminothiazole (2-AT) core as an active pharma-
cophore. Substituted aminothiazole compounds play a vital
role in the drug development and have a diverse range of
biological properties [22-28] including potential antitumor
activity [29-32]. Anticancer drugs Dabrafenib, Dasatinib and
Bleomycin are marketed widely in the world which contain
thiazole as an important structural element. The groove-
binding agents Dactinomycin, Netropsin and Thia-netropsin
are well known anticancer drugs with thiazole ring as an
important structural element [33]. It is evident from the lit-
erature, aminothiazoles acts as ligands for estrogen receptors
and novel class of adenosine receptor antagonists [34, 35]. It is
evident from the literature, amide containing heterocycles are
reported as a class of compounds displaying potential
biological activities, which consist of a vast number of natural
and synthetic products and are extremely versatile building
blocks for the manufacturing of bioactive compounds in
pharmaceutical drug development [36, 37].
Piperazine is a well-known six membered nitrogen con-
taining heterocyclic that can be found in a vast number of
marketed drug products including anticancer drugs. The
piperazine scaffold and its analogues hybrid systems have
gained much attention of the scientific community due to its
potential biological properties [38-43], especially antitumor
activity [44]. Slight structural alteration on the piperazine
pharmacophore facilitates as indispensable anchors for the
development of new chemical entities with a range of differ-
ent biological targets in medicinal chemistry [45, 46]. Louis
J. Lombardo and his co-workers reported the synthesis
of N-(2-Chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)-
piperazin-1-yl)-2-methylpyrimidin-4-ylamino) thiazole-5-
carboxamide (BMS-354825), a dual Src/Abl Kinase Inhibitor
with potent antitumor activity, which is widely used in the
cancer treatment with a brand name Sprycel (Dasatinib mono-
hydrate) which contain piperazine-thiazole scaffold [47]. Peter
L. Toogood and his team invented the best cancer drug,
6-Acetyl-8-cyclopentyl-5-methyl-2-{[5-(1-piperazinyl)-2-
pyridinyl] amino}pyrido[2,3-d]pyrimidin-7(8H)-one, brand
name Ibrance (Palbocilcib) that contains piperazine-pyridine
heterocyclic system [48].The well-known marketed alpha
blockers Terazosin, and Doxazosin comprise of the piperazine
structure. On the other hand, a large number of piperazine
scaffolds are reported with alpha blocking activity [49-52].
Isoxazoline is an important class of nitrogen and oxygen
containing five membered heterocycles belongs to azole
family. Substituted isoxazoles play a vital role in the drug
development and have a diverse range of biological proper-
ties [53-58] including antitumor activity [59].
Aforementioned endings in combining features of more
than one biologically active pharmacophores in a single
molecule may result in prominent pharmacological activity
while retaining high diversity and biological significance
[60-64]. On the basis of high-throughput screening, it was
envisaged to synthesize conjugate derivatives with amino-
thiazole, piperazine, pyridine and methyl isoxazoline
moieties in the same scaffold. The present study describes
the synthesis, characterization and antitumor activity evalua-
tion of 2-aminothiazoles bearing 5-methylisoxazoline and
pyridine-piperazine scaffolds.
2. RESULTS AND DISCUSSION
2.1. Chemistry
The key intermediate 5 for this study was prepared as
shown in Scheme 1. The first step of the synthesis involves the
condensation of ethyl acetoacetate 1 and triethylorthoformate
2 in presence of acetic anhydride resulted (Z)-ethyl 2-
(ethoxymethylene)-3-oxobutanoate 3 as a pale yellow liquid
in 63% yield. Further cyclization of 3 in presence of aqueous
hydroxylamine hydrochloride and alcoholic NaOH resulted
in ethyl 5-methylisoxazole-4-carboxylate 4 as a dark brown
liquid in 48% yield. Further hydrolysis of 4 in aqueous hy-
drochloric acid for 4h at reflux, yielded the key intermediate
5 as a pale yellow solid, in 71% yield [65]. Further chlorina-
tion with thionyl chloride [66] in refluxing toluene and cata-
lytic DMF result acid chloride 6. Further coupling of in situ
generated acid chloride 6 with different aryl amines 12a-e
yielded [67] the corresponding piperazine scaffolds 13a-e in
69-75% yields. All these newly synthesized compounds were
purified by column chromatography and characterized by
Mass, 1
H NMR and 13
C NMR.
3. Synthesis and Antitumor Activity Evaluation of 2-Aminothiazoles Letters in Organic Chemistry, 2018, Vol. 15, No. 0 3
O
O O OO
O
+
O O
O
O
NH2OH.HCl
N
O
OH
O
Ac2O
100-110°C
EtOH-NaOH
H2O-EtOH 80-85°c
6N HCl-reflux, 4 h
Toluene-Water
N
O
O
O
1
43
5
2
63% 48%
71%
Scheme (1). Synthetic route for key starting material (5).
S
N
O
OH2N
THF, 24h, rt
Boc2O, DMAP S
N
O
OBocHN
6N NaOH
THF-MeOH,
24h, rt, 81%
S
N
O
OHBocHN
1. (COCl)2,cat.DMF, DCM, THF, 4h, rt
DCM, DIPEA2.
3h, rt
Trifluoroacetic acid
N
N
N
R
H2N
N
N
N
R
N
H
N
S
BocHN
O N
N
N
R
N
H
N
S
H2N
O
N
O
O
OH
8 97
N
O
O
ClSOCl2-Toulene
5 6
10a-e
11a-e 12a-e
N
O
O
N
N
N
R
N
H
N
S
HN
OR =
N
O
O
O
OH
= =
=
=
13a-e
CH3
Toluene-Pyridine
65%
65-73%
85-93%
65-75%
Scheme (2). Synthesis of 2-aminothiazoles appended 5-methylisoxazoline and pyridine-piperazine derivatives (13a-e).
The five stage synthetic route for the target compounds
13a-e is depicted in Scheme 2. Briefly, the first step of the
synthesis involves the Boc protection of amine function in
Ethyl 2-aminothiazole-5-carboxylate 7 resulted compound 8
in 65% yield, which was further hydrolyzed with aqueous
NaOH in THF/MeOH gave acid 9 in 81% yield [67]. Boc
acid 9 was chlorinated with oxalyl chloride followed by in
situ coupling with aryl amine, 10a-e gave thiazole coupled
piperazine pyridine intermediates, 11a-e in 67-73%yield
[66]. Deprotection of Boc function of 11a-e in trifluoroacetic
acid yielded aminothiazole conjugates 12a-e in 85-93% yield
[32]. Finally, coupling of 12a-e with 5-methylisoxazole-4-
carboxylic acid 5 via in situ acid chloride 6, in pyridine and
refluxing toluene [66], gave the final compounds 13a-e in
69-75% yields (Table 2) as off white solid. All these newly
synthesized compounds were purified by column chromatog-
raphy and characterized by Mass, 1
H NMR and 13
C NMR.
2.1. Antiproliferative Activity
Antiproliferative activity of the final compounds, 13a-e
have been evaluated in vitro against four tumor cell lines,
namely MCF-7 (human breast adenocarcinoma), HCT-116
(colorectal carcinoma), Jurkat (human T-cell leukemia) and
THP-1 (human acute monocytic leukemia) using Sunitinib as
standard by following the MTT assay method [68].
In view of the structural diversity of 2-aminothiazoles
bearing 5-methylisoxazoline and pyridine-piperazine scaf-
folds, we mainly investigated the influence of R functional
group on piperazine heterocycles. All the synthesized com-
pounds showed potent activities against tested cancel cell
lines. Among the screened compounds, the rate of inhibition
was observed in the following order 13a > 13b > 13c > 13d
> 13e (Table 1) against THP 1 cancer cell lines. Among
these, compound 13a and 13b showed highest inhibition of
4. 4 Letters in Organic Chemistry, 2018, Vol. 15, No. 0 Suresh et al.
Table 1. In vitro cytotoxicity data of compounds 13a-e on MCF-7, HCT-116, Jurkat and THP-1 tumor cell lines.
IC50
a
(µM/L) ± SE
Compound
MCF-7 HCT-116 Jurkat THP-1
13a 6.4 + 0.31 5.9 + 0.29 8.3 + 0.92 2.9 + 0.32
13b 7.2 + 0.29 4.9 + 0.22 9.4 + 0.25 3.2 + 0.24
13c 8.4 + 0.18 4.8 + 0.28 7.4 + 0.86 3.9 + 0.54
13d 7.1 + 0.16 5.7 + 0.29 6.9 + 0.75 5.9 + 0.26
13e 8.3 + 0.24 6.7 + 0.28 9.9 + 0.52 6.8 + 0.51
Sunitinib 6.3+ 0.22 4.7 + 0.32 6.4 + 0.92 3.5 + 0.56
a
Concentration inhibiting fifty percent of cell growth for 72 h exposure period of tested samples. Assay was done in triplicate and mean values are presented.
Table 2. Yields of 2-aminothiazoles appended 5-methylisoxazoline and pyridine-piperazine derivatives (13a-e).
S. No. R Product Yield* (%)
1 OH
1 13a 69
2 N
O
1
13b 71
3 CH31 13c 70
4
O
1
13d 75
5
O
1
13e 73
proliferation activity against THP 1 cancer cell lines with
IC50 values 2.9 + 0.32 and 3.2 + 0.24, when compared to
reference standard drug Sunitinib. The better antiprolifera-
tive activity of compound 13a and 13b is due to the presence
of electron donating groups like 2-hydroxyethyl in 13a and
6-memebered morphine ring in 13b. The observed antipro-
liferation activity data showed that compounds containing
electron donating groups on aryl-piperazine ring are more
active compared to electron withdrawing carbonyl functional
groups on aryl-piperazine heterocyclic systems [69]. The
better activity by the compounds 13a and 13b could be at-
tributed to the cell permeability factor which is usually en-
hanced by electron donating functional group like 2-
hydroxyethyl functional substitution on aryl-piperazine het-
erocyclic systems [49].
3. EXPERIMENTAL
All of the chemicals were obtained from commercial
sources and used without further purification. Melting points
were determined in open glass capillaries on a Fisher–Johns
melting point apparatus and are uncorrected. NMR (1
H 400
MHz; 13
C 100 MHz) spectra were recorded at room tempera-
ture in DMSO and CDCl3 as solvent and TMS as an internal
standard (δ = 0 ppm), and the values were reported in the
following order: chemical shift (δ in ppm), multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet, qq
= quartet of quartet), coupling constants (J in Hz), and inte-
gration. All the reactions were monitored by thin layer
chromatography (TLC) on precoated silica gel 60 F254
(mesh); spots were visualized under UV light at 254 nm.
3.1. Typical Experimental Procedure for the Key Com-
pounds
3.1.1. 5-methylisoxazole-4-carboxylic acid (5)
To the stirred solution of 6N HCl (20.0 mL), ethyl 5-
methylisoxazole-4-carboxylate 4 (2.0 g, 0.0064 mol) was
added at 5-10°C and heated for 4 hours at 90-95°C. Reaction
completion was confirmed by TLC and charged with toluene
(30.0 mL) at 90-95°C. Further cooled to 25-30°C and stirred
for 5 hours, filtered the precipitated solid as a creamy solid.
Creamy solid charged in to a stirred 10% aqueous toluene
(150 ml) and heated to reflux, cooled to 40-45°C, filtered
and dried to give 5-methylisoxazole-4-carboxylic acid com-
pound 5 as off white solid 1.14 g (71%). MR: 136-138 °C;
1
H NMR spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz):
8.53 (s, 1H, thiazole-H), 2.74 (s, 3H, -CH3);13
C NMR spec-
trum (100 MHz, DMSO-d6), δ, ppm:169.7 (isoxazole-C),
167.9 (acid-C), 159.3 (isoxazole-C), 106.3 (isoxazole-C),
14.3 (CH3); MS (ESI) m/z 127.9 [M + H], 149.9 [M + Na].
5. Synthesis and Antitumor Activity Evaluation of 2-Aminothiazoles Letters in Organic Chemistry, 2018, Vol. 15, No. 0 5
3.1.2. Ethyl 2-((tert-butoxycarbonyl)amino)thiazole-5-
carboxylate (8)
To the stirred solution of ethyl 2-amino-4-
methylthiazole- 5-carboxylate 7 (5.0 g, 0.0290 mol) in dry
THF (65.0 mL), Boc-anhydride (7.6 g, 0.0348 mol) and cata-
lytic amount of 4-DMAP (177 mg, 0.0145 mol) were added
at 25-30°C. The reaction mass warmed up to 40-45°C and
stirred for 8 hours. The reaction mixture was concentrated.
The residue was dissolved in ethyl acetate (150.0 mL), and
washed with 2N HCl, DM water, 10% aqueous NaCl solu-
tion, dried over sodium sulfate and concentration resulted
creamy solid. Further recrystallization in ethyl acetate and
hexane resulted 8 (5.18 g, 65%) as a pale yellow solid. 1
H
NMR spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz): 11.3
(s, 1H, N-H), 8.12 (s, 1H, thiazole), 4.21-4.11 (q, 2H), 1.49
(s, 9H, Boc-H), 1.28-1.23 (t, 3H); 13
C NMR spectrum (100
MHz, DMSO-d6), δ, ppm: 168.3 (ester-C), 163.2 (thiazole-
C), 158.3 (amide-C), 131.2 (thiazole-C), 119.9 (thiazole-C),
69.8 (Boc-C), 59.8 (CH2), 20.5 (3C, Boc-CH3), 15.2 (CH3);
MS (ESI) m/z 273.1 [M + H] +
.
3.1.3. 2-((tert-butoxycarbonyl)amino)thiazole-5-carboxylic
acid (9)
To the stirred solution of ester 8, (4.5 g, 0.0165 mol) in
1:1 (72.0 mL) THF-Methanol, 3.3 g of NaOH dissolved in
45.0 mL water was added at 25-30°C. The reaction mass was
warmed to 60-65°C and stirred for 3 hours. Solvent was dis-
tilled under vacuum and charged with 45.0 mL water. The
reaction mass was cooled to 0-5°C and adjusted the reaction
mass pH to 3.2 with citric acid (15.8 g, 0.0826) and stirred
for 1h. The precipitated solid was filtered, washed with wa-
ter, 20% acetone-MTBE solution, yielded the compound 9
(3.24 g, 81%) as a pale yellow solid. 1
H NMR spectrum (400
MHz, DMSO-d6), δ, ppm (J, Hz): 12.5 (bs, 1H, acid), 10.9
(s, 1H, NH), 8.4 (s, 1H, thiazole), 1.49 (s, 9H, Boc-H), 13
C
NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 171.3 (acid-
C), 165.3 (thiazole-C), 160.5 (amide-C), 134.2 (thiazole-C),
119.6 (thiazole-C), 70.2 (Boc-C), 20.5 (3C, Boc-CH3); MS
(ESI) m/z 245.1 [M + H] +
, 267.2 [M + Na].
3.1.4. tert-butyl (5-((5-(4-(2-hydroxyethyl)piperazin-1-
yl)pyridin-2-yl)carbamoyl)thiazol-2-yl)carbamate (11a)
To the stirred suspension of 9 (2.75 g, 0.01126 mol) in
dichloromethane, 2 M oxalyl chloride (6.7 mL, 0.0135 mol)
and DMF (0.12 mL) were added at 0-5°C and warmed to 25-
30°C and stirred for 2 hours. The reaction mass was concen-
trated and the obtained residue was dissolved in ethyl acetate
(50.0 mL) and washed with 2N HCl, DM water, 10% aque-
ous NaCl solution, dried over sodium sulfate and concen-
trated, resulted pale yellow residual mass, treated with ethyl
acetate and hexane resulted acid chloride (2.8 g, 95%) as a
pale yellow solid, suspended in toluene (42.0 mL) and
cooled to 15-20°C and charged commercially available 2-(4-
(6-aminopyridin-3-yl)piperazin-1-yl)ethanol 10a (2.36 g,
0.01062 mol), diisopropylethylamine (4.6 mL, 0.0266 mol)
and catalytic DMAP. Reaction mass was heated for 3 hours
at reflux. Cooled the reaction mass to 25-30°C filtered the
solid 11a (3.2 g, 67%) as a pale yellow solid.
1
H NMR spectrum (400 MHz, DMSO-d6), δ, ppm (J,
Hz): 11.32 (s, 1H, Boc-NH), 10.98 (bs, 1H, amide-NH), 8.92
(s, 1H, thiazole-H), 7.69 (d, 1H, pyridine-H), 7.36-7.34 (m,
2H, pyridine-H), 4.41 (t, 1H, -OH), 3.54-3.51 (m, 6H, -
CH2CH2OH & piperazine-CH2), 2.39-2.32 (m, 6H, -
CH2CH2OH & piperazine-CH2) 1.42 (s, 9H, Boc-H); 13
C
NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 160.6
(thiazole-C), 159.1 (amide-C), 153.2 (Boc amide-C), 141.9
(pyridine-C), 136.9 (thiazole-C), 135.2 (pyridine-C), 129.5
(pyridine-C), 127.9 (pyridine-C), 125.3 (thiazole-C), 112.3
(pyridine-C), 71.2 (Boc-CH), 59.7 (CH2), 58.9 (CH2), 51.1
(piperazine-2C), 39.7 (piperazine-2C), 29.3 (CH3-3C); MS
(ESI) m/z 449.1[M + H] +
; Anal. Calcd % for C20H28N6O4S:
C 53.56; H 6.29; N 18.74. Found: C 53.45; H 6.31; N 18.63.
Following the same procedure as illustrated for 11a the
other Boc protected 2-aminothiazoles 11b-e were prepared
by coupling 9 with corresponding amino pyridines 10b-e.
3.1.5. 2-amino-N-(5-(4-(2-hydroxyethyl)piperazin-1-
yl)pyridin-2-yl)thiazole-5-carboxamide (12a)
To the stirred solution of trifluoroacetic acid (22.0 mL),
compound 11a (2.75 g, 0.00613) was added at 0-5°C. The
reaction mass warmed to 25-30°C and stirred for 2 hours.
The reaction mass was concentrated and charged with water
(25.0 mL) and 10% NaHCO3 solution (50.0 mL) and stirred
for 3 hours. Filtered the solid and washed the wet cake with
10% acetone water solution, obtained the compound 12a as a
pale yellow solid (1.9 g). Further recrystallization in 85%
Methanol/water (160.0 mL), obtained the compound 12a
(1.82 g, 86%) as an off white solid.
1
H NMR spectrum (400 MHz, DMSO-d6), δ, ppm (J,
Hz): 10.91 (bs, 1H, amide-NH), 8.26 (s, 1H, thiazole-H),
7.74 (d, 1H, pyridine-H), 7.30-7.23 (m, 2H, pyridine-H),
7.12 (bs, 2H, NH2), 4.32 (t, 1H, -OH), 3.59-3.63 (m, 6H, -
CH2CH2OH & piperazine-CH2), 2.45-2.41 (m, 6H, -
CH2CH2OH & piperazine-CH2); 13
C NMR spectrum (100
MHz, DMSO-d6), δ, ppm: 165.3 (thiazole-C), 159.7 (amide-
C), 141.3 (pyridine-C), 138.9 (thiazole-C), 134.6 (pyridine-
C), 131.9 (pyridine-C), 129.4 (pyridine-C), 127.6 (thiazole-
C), 115.3 (pyridine-C), 60.8 (CH2), 59.3 (CH2), 51.6
(piperazine-2C), 39.1 (piperazine-2C); MS (ESI) m/z 349.1
[M + H] +
; Anal. Calcd % for C15H20N6O2S: C 51.71; H 5.79;
N 24.12. Found: C 51.68; H 5.77; N 24.17.
Following the same procedure as depicted for 12a the
other derivatives 12b-e were prepared from the corresponding
Boc protected 2-aminothiazoles 11b-d.
3.1.6. N-(5-((5-(4-(2-hydroxyethyl)piperazin-1-yl)pyridin-2-
yl)carbamoyl)thiazol-2-yl)-5-methylisoxazole-4-carbox-
amide (13a)
5-methylisoxazole-4-carboxylic acid 5 (1.0 g, 0.00786
mol) and catalytic amount of DMF (0.05) were added to the
stirred solution of thionyl chloride (3.0 mL) at 25-30°C [46].
Reaction mass was heated under reflux for 3 hours and con-
centrated. The residue was distilled through a fractionating
column by collecting the acid chloride (0.59 g, 52%) at 68-
71°C in 11 mm Hg vacuum. Acid chloride fraction (0.59 g)
was taken in toluene (12.0 mL) and cooled to 5-10°C and
charged with 5-amino-N-(5-(4-(2-hydroxyethyl)piperazin-1-
6. 6 Letters in Organic Chemistry, 2018, Vol. 15, No. 0 Suresh et al.
yl)pyridin-2-yl)thiazole-2-carboxamide 12a (1.41 g, 0.0040
mol). Pyridine (1.8 mL, 0.0223) added slowly to the stirred
reaction mass at 5-10°C, over 1-2 minutes. Reaction mass
was heated to reflux and stirred for 3 hours and concentrated.
The residue was purified by column chromatography using
methanol/dichloromethane/triethyl amine eluent, yielded the
target compound 13a as an off white solid (1.27 g, 69%).
MR: 265-267°C; 1
H NMR spectrum (400 MHz, DMSO-
d6), δ, ppm (J, Hz): 11.47 (bs, 1H, amide-NH), 9.88 (s, 1H,
amide-NH), 8.49 (s, 1H, thiazole-H), 8.22 (s, 1H, isoxazole-
H), 7.39 (t, 1H, pyridine-H), 7.30-7.23 (m, 2H, pyridine-H),
4.46 (t, 1H, -OH), 3.54-3.51 (m, 6H, -CH2CH2OH &
piperazine-CH2), 2.48-2.46 (m, 4H, piperazine-CH2), 2.44-
2.42 (m, 2H, -CH2CH2OH), 2.40 (s, 3H, ioxazole-CH3); 13
C
NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 165.1
(isoxazole-C), 162.5 (amide-C), 162.3 (thiazole-C), 159.9
(amide-C), 156.9 (isoxazole-C), 140.8 (pyridine-C), 138.8
(thiazole-C), 133.5 (pyridine-C), 132.4 (pyridine-C), 129.0
(pyridine-C), 128.1 (thiazole-C), 126.9 (pyridine-C), 98.8
(isoxazole-C), 60.1 (CH2), 58.5 (CH2), 52.7 (piperazine-2C),
43.6 (piperazine-2C), 18.29 (CH3); MS (ESI) m/z 458.1 [M +
H] +
; Anal. Calcd % for C20H23N7O4S: C 52.51; H 5.07; N
21.43. Found: C 52.49; H 5.12; N 21.45.
Following the same procedure as illustrated for 13a the
other 2-aminothiazoles appended 5-methylisoxazoline and
pyridine-piperazine derivatives 13b-e were prepared by
coupling 5 with corresponding amines 12b-e. The physical,
spectral, and analytical data for these compounds are
mentioned as follows.
3.1.6.1. 5-methyl-N-(5-((5-(4-(2-morpholinoethyl)pipera-
zin-1-yl)pyridin-2-yl)carbamoyl)thiazol-2-yl)isoxazole-4-
carboxamide (13b)
(1.25 g, 71%); MR: 279-281°C; 1
H NMR spectrum (400
MHz, DMSO-d6), δ, ppm (J, Hz): 11.49 (bs, 1H, amide-
NH), 9.85 (s, 1H, amide-NH), 8.71 (s, 1H, thiazole-H), 8.24
(s, 1H, isoxazole-H), 7.43 (t, 1H, pyridine-H), 7.31-7.24 (m,
2H, pyridine-H), 3.55-3.52 (m, 6H, morpholine &
piperazine-CH2), 3.34-3.36 (m, 2H, piperazine-CH2), 3.15-
3.11 (m, 4H, piperazine-CH2), 2.49-2.45 (m, 4H,
morpholine-CH2), 2.43 (t, 2H, methylene -CH2), 2.40 (t, 2H,
methylene -CH2), 2.15 (s, 3H, -CH3); 13
C NMR spectrum
(100 MHz, DMSO-d6), δ, ppm: 165.1 (isoxazole-C), 162.6
(amide-C), 162.4 (thiazole-C), 159.9 (amide-C), 156.9
(isoxazole-C), 140.9 (pyridine-C), 138.8 (thiazole-C), 133.5
(pyridine-C), 132.4 (pyridine-C), 129.0 (pyridine-C), 128.1
(thiazole-C), 127.0 (pyridine-C), 97.0 (isoxazole-C), 66.4
(morpholine-2C), 61.3 (morpholine-2C), 60.23 (methylene-
1C), 58.5 (methylene-C), 52.7 (piperazine-2C), 43.6
(piperazine-2C), 18.3 (CH3); MS (ESI) m/z 527.1 [M + H] +
;
Anal. Calcd % for C24H30N8O4S: C 54.74; H 5.74; N 21.28.
Found: C 54.71; H 5.69; N 21.31.
3.1.6.2. 5-methyl-N-(5-((5-(4-methylpiperazin-1-yl)pyridin-
2-yl)carbamoyl)thiazol-2-yl)isoxazole-4-carboxamide (13c)
(1.31 g, 70%); MR: 243-246°C; 1
H NMR spectrum (400
MHz, DMSO-d6), δ, ppm (J, Hz): 11.15 (bs, 1H, amide-
NH), 9.90 (s, 1H, amide-NH), 8.69 (s, 1H, thiazole-H), 8.23
(s, 1H, isoxazole-H), 7.40-7.38 (m, 1H, pyridine-H), 7.29-
7.23 (m, 2H, pyridine-H), 2.86-2.80 (m, 4H, piperazine-
CH2), 2.79-2.78 (m, 4H, piperazine-CH2), 2.40 (s, 3H,
ioxazole-CH3), 2.23 (s, 3H, N-CH3); 13
C NMR spectrum
(100 MHz, DMSO-d6), δ, ppm: 165.6 (isoxazole-C), 163.0
(amide-C), 162.7 (thiazole-C), 160.4 (amide-C), 157.4
(isoxazole-C), 154.3 (pyridine-C), 141.3 (thiazole-C), 139.2
(pyridine-C), 134.0 (pyridine-C), 132.9 (pyridine-C), 129.4
(thiazole-C), 128.6 (pyridine-C), 99.5 (isoxazole-C), 61.1
(piperazine-2C), 43.7 (piperazine-2C), 38.5 (N-CH3), 16.0
(CH3); MS (ESI) m/z 428.1 [M + H] +
; Anal. Calcd % for
C19H21N7O3S: C 53.38; H 4.95; N 22.94. Found: C 53.29; H
4.87; N 23.03.
3.1.6.3. N-(5-((5-(4-acetylpiperazin-1-yl)pyridin-2-
yl)carbamoyl)thiazol-2-yl)-5-methylisoxazole-4-
carboxamide (13d)
(1.37 g, 75%); MR: 257-259°C; 1
H NMR spectrum (400
MHz, DMSO-d6), δ, ppm (J, Hz): 11.31 (bs, 1H, amide-
NH), 9.89 (s, 1H, amide-NH), 8.44 (s, 1H, thiazole-H), 8.22
(s, 1H, isoxazole-H), 7.41-7.39 (m, 1H, pyridine-H), 7.30-7.24
(m, 2H, pyridine-H), 3.44 (m, 4H, piperazine-CH2), 2.75-2.73
(m, 4H, piperazine-CH2), 2.40 (s, 3H, ioxazole-CH3), 2.24 (s,
3H, acetyl-CH3); 13
C NMR spectrum (100 MHz, DMSO-d6),
δ, ppm: 167.0 (isoxazole-C), 165.1 (acetyl-C), 162.6 (amide-
C), 162.5 (thiazole-C), 159.9 (amide-C), 156.9 (isoxazole-
C), 140.8 (pyridine-C), 138.8 (thiazole-C), 133.5 (pyridine-
C), 132.4 (pyridine-C), 129.0 (pyridine-C), 128.1 (thiazole-
C), 127.0 (pyridine-C), 98.4 (isoxazole-C), 45.2 (piperazine-
2C), 44.7 (piperazine-2C), 25.6 (acetyl-CH3), 18.3 (CH3);
MS (ESI) m/z 456.1 [M + H] +
; Anal. Calcd % for
C20H21N7O4S: C 52.74; H 4.65; N 21.53. Found: C 52.69; H
4.69; N 21.61.
3.1.6.4. N-(5-((5-(4-(cyclopropanecarbonyl)piperazin-1-
yl)pyridin-2-yl)carbamoyl)thiazol-2-yl)-5-methylisoxazole-
4-carboxamide (13e)
(1.31 g, 73%); MR: 259-261°C; 1
H NMR spectrum (400
MHz, DMSO-d6), δ, ppm (J, Hz): 11.51 (bs, 1H, amide-
NH), 9.91 (s, 1H, amide-NH), 8.75 (s, 1H, thiazole-H), 8.25
(s, 1H, isoxazole-H), 7.47-7.41 (m, 1H, pyridine-H), 7.35-
7.31 (m, 2H, pyridine-H), 3.56-3.51 (m, 4H, piperazine-
CH2), 2.89-2.85 (m, 4H, piperazine-CH2), 2.40 (s, 3H,
ioxazole-CH3), 1.48-1.46 (m, 1H, cyclopropyl-CH), 0.89-
0.79 (m, 4H, cyclopropyl-CH2); 13
C NMR spectrum (100
MHz, DMSO-d6), δ, ppm: 170.4 (isoxazole-C), 165.6
(acetyl-C), 163.0 (amide-C), 162.8 (thiazole-C), 160.4
(amide-C), 157.4 (isoxazole-C), 141.3 (pyridine-C), 139.3
(thiazole-C), 134.0 (pyridine-C), 132.9 (pyridine-C), 129.4
(pyridine-C), 128.6 (thiazole-C), 127.4 (pyridine-C), 98.6
(isoxazole-C), 60.4 (piperazine-2C), 58.6 (piperazine-2C),
26.0 (CH3), 18.7 (cyclopropyl-CH), 13.1 (cyclopropyl-2C);
MS (ESI) m/z 482.0 [M + H] +
; Anal. Calcd % for
C20H23N7O4S: C 54.88; H 4.81; N 20.36. Found: C 54.85; H
4.86; N 20.43.
4. SCREENING OF ANTIPROLIFERATIVE ACTI-
VITY
Antiproliferative activity of the final compounds 13a-e
has been evaluated in vitro against four tumor cell lines, by
7. Synthesis and Antitumor Activity Evaluation of 2-Aminothiazoles Letters in Organic Chemistry, 2018, Vol. 15, No. 0 7
using following MTT assay method [68] (MTT; 3-(4, 5-
dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide).
All cancer cell lines (MCF-7, HCT-116, Jurkat and THP-1)
were cultured in Roswell Park Memorial Institute (RPMI)
1640 Medium with heat inactivated Fetal Bovine Serum
(FBS) (10%) and 1% Pen/Strep in a humidified atmosphere
of 95% air and 5% CO2 at 37°C for 72 hours. Primarily, each
test compound of 10.0 mg was dissolved in 1.0 mL of
DMSO and further diluted to obtain required experimental
stock concentrations from 0.01 to 0.1% and obtained the
final volume of 250.0 mL. Briefly, cells were seeded in 96
well microtiter plates at a density of 2 X 106
cells per well
with 0.1 mL of RPMI medium. After 72 hours the inhibition
of cell proliferation was determined by treating cells against
tested compounds 13a-e at different concentrations and the
cell viability was assessed after 48 h, by adding 10 µL per
well of MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl
tetrazolium bromide). The plates were incubated at 37°C for
additional 5 hours. Discarded the medium and the obtained
formazan blue in the cells, was dissolved with DMSO for 10
minutes with gentle agitation. The rate of colour production
was measured at 570 nm in a spectrophotometer. The assay
was done in triplicate and average values were recorded.
The concentrations that cause 50% of cell proliferation
inhibition, IC50 values were determined for each compound
from a regression equation, a plot of drug concentration
versus percentage loss of viability and the results were
summarized in Table 1.
CONCLUSION
In conclusion, we have successfully achieved two impor-
tant aspects of this work. One is a highly efficient and milder
protocol for the synthesis of 2-aminothiazoles bearing
5-methylisoxazoline and pyridine-piperazine scaffolds 13a-e
in good yields. The second one is the coupling of different
pharmacophores, each endowed with diverse biological
properties resulted in hybrid molecules with significant
antitumor activity. Interestingly, all these new compounds are
active and showed moderate to good activity against tested
cancel cell lines. The observed activity profile suggested that
the presence of electron donating functional group enhanced
the anticancer activity compared to electron withdrawing
groups on piperazine heterocyclic. In conclusion, based on the
observed antiproliferative activity data compounds 13a and
13b could be further developed in to potential anticancer
drugs.
CONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
Declared none.
SUPPLEMENTARY MATERIAL
Supplementary material is available on the publisher’s
website along with the published article. Spectra of key
compounds were attached as a separate file.
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