The document discusses the synthesis and biological evaluation of novel 1,4-diaryl-substituted triazole derivatives as selective COX-2 inhibitors. Three categories of compounds were synthesized using click chemistry, varying the length of an alkyl linker between the triazole and aryl rings. Category I compounds with no linker showed good COX-2 potency and selectivity. Category II compounds with one carbon linker produced the most potent and selective COX-2 inhibitor. Category III compounds with a two-carbon linker resulted in compound 30, the most potent COX-2 inhibitor identified. Molecular modeling suggested compound 30's increased flexibility allows its sulfonamide group to deeper bind in the COX-2 active site, correlating with
This document discusses the design and biological evaluation of heterocyclic quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2). Key points:
1) There is a need for new antimalarial drugs with novel mechanisms of action to address rising drug resistance. Targeting PfNDH2 is a novel mechanism with potential for curative activity.
2) A screening campaign identified monoaryl quinolones as hits against PfNDH2. Medicinal chemistry optimization incorporated heterocycles like pyridine to reduce drug likeness properties and enhance potency and solubility, yielding lead compound SL-2-25 with low nan
Cyclooxygenase (COX) is an enzyme that catalyzes the formation of prostanoids like thromboxane and prostaglandins from arachidonic acid. It exists in two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed while COX-2 is inducible during inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes to exert their effects. Kinetic studies show that nitric oxide can increase the activity of COX-2 but not COX-1 by enhancing its maximum reaction rate and decreasing its Michaelis constant for oxygen. Understanding the differences between COX-1 and COX-2
This document summarizes research on a novel tetra nuclear copper (II) complex (compound 2) and its potential anticancer properties. In vitro studies showed compound 2 exhibited significant cytotoxic effects on rat L6 myotubes, mouse NSC-34 motor neurone-like cells, and HepG-2 human liver carcinoma cells after 96 hours, inducing both apoptosis and necrosis. Compound 2 displayed better potency and efficacy than the drug cisplatin. Additionally, compound 2 demonstrated significant superoxide dismutase (SOD) mimetic activity during shorter incubations, more so than the known SOD mimetic TEMPOL. The document concludes compound 2 has potential as a new anticancer drug through SOD-mimetic redo
COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.Coxibs are NSAIDs that are highly selective for the COX2 enzyme. Because the COX2 enzyme mediates prostaglandin production responsible for inflammation and pain, coxibs are analgesic and antiinflammatory, but they lack the side effects related to inhibiting the COX1 enzyme (e.g., bleeding and gastrointestinal irritation).
One pot synthesis of cu(ii) 2,2′ bipyridyl complexes of 5-hydroxy-hydurilic acidrkkoiri
This document describes the one-pot synthesis of two new copper(II) complexes containing the ligands 5-hydroxy-hydurilic acid (complex 1) and alloxanic acid (complex 2) from the reaction of a barbiturate derivative (LH4) with Cu(II) 2,2'-bipyridyl complexes. It also reports the synthesis of a third complex (complex 3) from the reaction of LH4 with copper nitrate that retains the ligand framework. The complexes were characterized using X-ray crystallography, spectroscopy, and electrochemistry. Complexes 1 and 3 were found to cleave DNA and showed cytotoxic activity against cancer cells, while complex 2 was insoluble and not
One pot synthesis of cu(ii) 2,2′ bipyridyl complexes of 5-hydroxy-hydurilic acidrkkoiri
This document describes the one-pot synthesis of three copper(II) complexes with 2,2'-bipyridine and derivatives of a barbiturate ligand. Complex 1 contains 5-hydroxy-hydurilic acid, complex 2 contains alloxanic acid, and complex 3 retains the original barbiturate ligand framework. The complexes were characterized using X-ray crystallography, spectroscopy, and thermal analysis. Their interactions with DNA were studied through absorption and emission titrations as well as circular dichroism. Complexes 1 and 3 were found to cleave plasmid DNA. Their cytotoxicity against T-cell lymphoma cells was also evaluated.
This document provides an overview of 1,2,3-triazoles and their biological activities. It discusses various synthetic strategies for producing 1,2,3-triazoles, including Huisgen cycloaddition and palladium-catalyzed reactions. The document then summarizes research on the anticancer, anti-inflammatory, antitubercular, antiviral, and antibacterial activities of 1,2,3-triazole derivatives, noting several potent compounds and their mechanisms of action.
This document discusses the design and biological evaluation of heterocyclic quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2). Key points:
1) There is a need for new antimalarial drugs with novel mechanisms of action to address rising drug resistance. Targeting PfNDH2 is a novel mechanism with potential for curative activity.
2) A screening campaign identified monoaryl quinolones as hits against PfNDH2. Medicinal chemistry optimization incorporated heterocycles like pyridine to reduce drug likeness properties and enhance potency and solubility, yielding lead compound SL-2-25 with low nan
Cyclooxygenase (COX) is an enzyme that catalyzes the formation of prostanoids like thromboxane and prostaglandins from arachidonic acid. It exists in two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed while COX-2 is inducible during inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes to exert their effects. Kinetic studies show that nitric oxide can increase the activity of COX-2 but not COX-1 by enhancing its maximum reaction rate and decreasing its Michaelis constant for oxygen. Understanding the differences between COX-1 and COX-2
This document summarizes research on a novel tetra nuclear copper (II) complex (compound 2) and its potential anticancer properties. In vitro studies showed compound 2 exhibited significant cytotoxic effects on rat L6 myotubes, mouse NSC-34 motor neurone-like cells, and HepG-2 human liver carcinoma cells after 96 hours, inducing both apoptosis and necrosis. Compound 2 displayed better potency and efficacy than the drug cisplatin. Additionally, compound 2 demonstrated significant superoxide dismutase (SOD) mimetic activity during shorter incubations, more so than the known SOD mimetic TEMPOL. The document concludes compound 2 has potential as a new anticancer drug through SOD-mimetic redo
COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.Coxibs are NSAIDs that are highly selective for the COX2 enzyme. Because the COX2 enzyme mediates prostaglandin production responsible for inflammation and pain, coxibs are analgesic and antiinflammatory, but they lack the side effects related to inhibiting the COX1 enzyme (e.g., bleeding and gastrointestinal irritation).
One pot synthesis of cu(ii) 2,2′ bipyridyl complexes of 5-hydroxy-hydurilic acidrkkoiri
This document describes the one-pot synthesis of two new copper(II) complexes containing the ligands 5-hydroxy-hydurilic acid (complex 1) and alloxanic acid (complex 2) from the reaction of a barbiturate derivative (LH4) with Cu(II) 2,2'-bipyridyl complexes. It also reports the synthesis of a third complex (complex 3) from the reaction of LH4 with copper nitrate that retains the ligand framework. The complexes were characterized using X-ray crystallography, spectroscopy, and electrochemistry. Complexes 1 and 3 were found to cleave DNA and showed cytotoxic activity against cancer cells, while complex 2 was insoluble and not
One pot synthesis of cu(ii) 2,2′ bipyridyl complexes of 5-hydroxy-hydurilic acidrkkoiri
This document describes the one-pot synthesis of three copper(II) complexes with 2,2'-bipyridine and derivatives of a barbiturate ligand. Complex 1 contains 5-hydroxy-hydurilic acid, complex 2 contains alloxanic acid, and complex 3 retains the original barbiturate ligand framework. The complexes were characterized using X-ray crystallography, spectroscopy, and thermal analysis. Their interactions with DNA were studied through absorption and emission titrations as well as circular dichroism. Complexes 1 and 3 were found to cleave plasmid DNA. Their cytotoxicity against T-cell lymphoma cells was also evaluated.
This document provides an overview of 1,2,3-triazoles and their biological activities. It discusses various synthetic strategies for producing 1,2,3-triazoles, including Huisgen cycloaddition and palladium-catalyzed reactions. The document then summarizes research on the anticancer, anti-inflammatory, antitubercular, antiviral, and antibacterial activities of 1,2,3-triazole derivatives, noting several potent compounds and their mechanisms of action.
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.
This Journal publishes original research work that contributes significantly to further the scientific knowledge in pharmacy.
The document summarizes the role of prostaglandins. It discusses that prostaglandins are derived from arachidonic acid and are involved in various physiological processes and the inflammatory response. They act as local signaling molecules and are generated through the cyclooxygenase pathway. Nonsteroidal anti-inflammatory drugs inhibit this pathway and thereby reduce prostaglandin production and downstream inflammatory effects. The document also outlines prostaglandin nomenclature and biosynthesis.
This document describes a study that synthesized novel 2,3-dihydro-1H-inden-1-one chalcone-like compounds and their hydroxyl derivatives to evaluate their inhibitory effects on mushroom tyrosinase activity. Two compounds, 2a and 2b, inhibited tyrosinase's diphenolase activity in a dose-dependent manner, with IC50 values lower than the positive control, kojic acid. Kinetic analysis showed that compounds 2a and 2b are reversible competitive inhibitors of tyrosinase. Compound 2b, with a 3,4-dihydroxy group resembling the substrate L-DOPA, exhibited the most potent inhibition, suggesting hydroxy-substituted 2,
This study synthesized and characterized Schiff base transition metal complexes of cobalt(II) and copper(II) acetylacetonate (acac) ligands. The cobalt(II) and copper(II) acac complexes were tested for their antimicrobial properties against bacteria and fungi. Both complexes showed little to no inhibitory effects on the microbes tested. Their structures were characterized through UV-Vis spectroscopy, which identified maximum absorbances of 491 nm for cobalt(II) acac and 632 nm for copper(II) acac.
In-vitro biological activities of the free new H4L ( indole-7-thiocarbohydrazone) ligand and its Ni(II), Pd(II) , Pt(II),
Cu(II), Ag(I), Zn(II) and Cd(II) complexes are screened against two cancerous cell lines, that revealed significant
activity only for [Cu2Cl2(H4L)2(PPh3)2] after 72 h treatment by the highest tested concentrations. The Copper(I)
complex was characterized by X-ray Crystallography and the NMR spectra, whereas it has been confirmed to have
momentous cytotoxicity against ovarian, breast cancerous cell lines (Caov-3, MCF-7). The apoptosis-inducing
properties of the Cu(I) complex have been investigated through fluorescence microscopy visualization, DNA
fragmentation analysis and propidium iodide flow cytometry.
Anticancer Activity of New Di-Nuclear Copper (I) ComplexTaghreed Al-Noor
In-vitro biological activities of the free new H4L ( indole-7-thiocarbohydrazone) ligand and its Ni(II), Pd(II) , Pt(II),
Cu(II), Ag(I), Zn(II) and Cd(II) complexes are screened against two cancerous cell lines, that revealed significant
activity only for [Cu2Cl2(H4L)2(PPh3)2] after 72 h treatment by the highest tested concentrations. The Copper(I)
complex was characterized by X-ray Crystallography and the NMR spectra, whereas it has been confirmed to have
momentous cytotoxicity against ovarian, breast cancerous cell lines (Caov-3, MCF-7). The apoptosis-inducing
properties of the Cu(I) complex have been investigated through fluorescence microscopy visualization, DNA
fragmentation analysis and propidium iodide flow cytometry.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, 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.
This document summarizes recent research on using gold nanoclusters (Au NCs) for biomedical applications. It discusses how Au NCs that are less than 6 nm in size can be cleared renally due to their ultra-small size. Their tunable photoluminescence from UV to near-infrared makes them suitable for multimodal imaging. The document reviews methods for synthesizing different types of Au NCs stabilized by various ligands and discusses parameters that influence their behavior after administration in small animals. It presents recent advances in using Au NCs as theranostic agents and compares them to other contrast agents.
During favorable conditions, the level of reactive spices in the cell is limited to what is required for normal cellular activities. They act as important components of signaling pathways. Plants control some important processes such as defense, hormonal signaling and development by using them as signaling molecules. And An equilibrium is steblished between antioxidant system and ros formation. But when plant feels an external stress like, drought,cold, salt etc. the level of reactive specease increases above the basal level a situation that we call oxidative stress. These reactive molecules during oxidative stress, they react with biomolecules like as carbohydrates, unsaturated lipids, proteins, nucleic acids. Proteins are the most abundant cellular targets of the oxidative species, more than DNA and lipids, making up 68% of the oxidized molecules in the cell. Ros reacts with proteins which results in protein modification called redox PTMs.
This document summarizes the synthesis and characterization of lanthanide complexes with the drug cloxacillin. Cloxacillin is an antibiotic drug that is commonly used to treat bacterial infections. Seven lanthanide complexes of the form [Ln(Clox)2(H2O)2]Cl where Ln = La(III), Pr(III), Nd(III), Sm(III), Dy(III), Ho(III) and Er(III) were synthesized. The complexes were characterized using elemental analysis, infrared spectroscopy, electronic spectroscopy, magnetic susceptibility measurements, and thermal analysis. Elemental analysis showed a 1:2 metal to ligand ratio in the complexes. Infrared spectroscopy indicated that cloxacillin binds in
Synthesis, characterization, amdet and docking studies of novel diclofenac de...Alexander Decker
This document discusses the synthesis and characterization of novel diclofenac derivatives containing phenylalanine moieties as selective inhibitors of cyclooxygenase-2 (COX-2). Sixteen novel diclofenac derivatives were synthesized and their structures were confirmed through various analytical techniques. Molecular docking studies predicted that compounds 7, 12 and 16 showed stronger binding with COX-2 than the reference drug diclofenac, making them potential selective COX-2 inhibitors. The binding scores of these compounds were higher than diclofenac when docked into the active site of COX-2.
Detailed characterization of saponins isolated from Zygophyllum Propinqueem D...Open Access Research Paper
Zygophyllum propinquum Decne (syn. Z. coccineum, family: Zygophyllaceae) is a low shrub, perennial herb, or desert succulent undershrub and has several important biological activities. The major secondary metabolites of this plant are a class of ursane-type triterpene saponins. Saponins derive their name from stable foam formation in water. These saponins have peculiar properties like, bitterness, fish poisoning, haemolysis, complex formation with cholesterol. Saponins are consisting of two main parts, one is the aglycone part while the other one is the glycone part. The glycone part is further consisting of sugar moieties. Current studies were conducted to isolate specifically biologically important saponins. Saponins were isolated successfully using standard procedures and characterized successfully using different spectroscopic techniques including Fourier Transform-Infrared Spectroscopy, Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy. Two saponins were isolated from the whole plant of Zygophyllum propinquum Decne with the help of repeated column chromatography and HPLC. The purified saponins were hydrolyzed with H2SO4-dioxane resulting in lactone formation. All the compounds (saponins and lactone) were characterized with the help of FAB-MS and 1D and 2D-NMR techniques. Their structures were confirmed to be 3-O–β-D-glucopyranosyl-(1→6)- β-D-2-O-sulfo-glucuronopyranosylurs-20(21)-en28 oic acid 28-O-[β-D-glucuronopyranosyl] ester (1), (3β–O-2-O-sulfo-β-D-glucuronopyranosylurs-20(21)-en28 oic acid 28-O-[β-D-2-O-sulfonylglucuronopyranosyl] ester (2), and 3β-Hydroxy urs-28,20 β-olide (3).
This study synthesized a series of hydroxy-substituted chalcone oxime derivatives and evaluated their inhibitory effects on tyrosinase and melanin formation in mouse melanoma cells. Two compounds exhibited much stronger tyrosinase inhibition than the positive control kojic acid. Kinetic studies showed that these compounds act as competitive tyrosinase inhibitors by binding to the enzyme's active site. Both compounds inhibited tyrosinase activity and melanin production in mouse melanoma cells, suggesting their potential as skin lightening agents.
This document discusses a study on the inhibitive properties and quantum chemical analysis of 1,4-benzothiazine derivatives for corrosion inhibition of mild steel in acidic medium. Two derivatives, compounds P3 and P4, were synthesized and their structures were confirmed through various analytical techniques. Electrochemical tests including polarization, electrochemical impedance spectroscopy, and weight loss measurements were used to evaluate the corrosion inhibition efficiency of P3 and P4 in 1 M HCl solution. Quantum chemical calculations based on density functional theory were also performed to correlate inhibition efficiency with molecular properties. The results showed that P3 and P4 acted as efficient corrosion inhibitors for mild steel in acidic solution, with inhibition efficiency increasing with increasing concentration. Adsorption
This document discusses an enzyme called cyclooxygenase. Prostaglandin Endoperoxide H Synthase (Commonly known as "Cyclooxygenase") is an enzyme essential for immune response and mainly, in prostaglandin biosynthesis (a metabolic pathway in Arachidonic acid metabolism). Read the document for further information.
SiO2@FeSO4 nano composite: A recoverable nano-catalyst for eco-friendly synth...Iranian Chemical Society
Various aldoximes and ketoximes synthesis of corresponding aldehydes and ketones in the presence of SiO2@FeSO4 nano composite as recoverable nano catalyst and NH2OH·HCl. The SiO2@FeSO4 nano composite system was carried out between 10 to 15 min in oil bath (70-80 °C) under solvent-free condition in excellent yields in addition this protocol can be used for industrial scales. This method offers some advantages in term of clean reaction conditions, easy work-up procedure, short reaction time, applied to convert α-diketones to α-diketoximes (as longer than other carbonyl compounds), α,β-unsaturated aldehydes and ketones to corresponding oximes and suppression of any side product. So we think that NH2OH•HCl/SiO2@FeSO4 nano composite system could be considered a new and useful addition to the present methodologies in this area. Structure of products and nano composite elucidation was carried out by 1H NMR, 13C NMR, FT-IR, scanning electron microscopy (SEM).
Organomercury compounds have a variety of applications despite their toxicity. This document discusses two recent research topics on the use of organomercury catalysts:
1) The development of organomercury haptens for enzyme-linked immunoassays to detect inorganic and organic mercury. Antibodies were successfully generated that could bind both mercury ions and organometallic forms of mercury.
2) A direct method for derivatizing disulfide bonds in proteins using organic mercury in alkaline medium without chemical pre-reducing agents. p-Hydroxymercurybenzoate was shown to effectively label disulfide groups in lysozyme, allowing for their one-step determination.
Overall, the document
1. krebs cycle activators, inhibitors and their roles in the modulation of ...kennyfranz1
The document discusses the Krebs cycle, which is a series of chemical reactions in mitochondria that breaks down nutrients to generate energy. It focuses on how the cycle produces molecules like NADH that fuel ATP production and provides reducing power to cells. The review examines the Krebs cycle pathways, key enzymes and reactions involved, and how activators and inhibitors can impact energy metabolism and carcinogenesis.
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.
This Journal publishes original research work that contributes significantly to further the scientific knowledge in pharmacy.
The document summarizes the role of prostaglandins. It discusses that prostaglandins are derived from arachidonic acid and are involved in various physiological processes and the inflammatory response. They act as local signaling molecules and are generated through the cyclooxygenase pathway. Nonsteroidal anti-inflammatory drugs inhibit this pathway and thereby reduce prostaglandin production and downstream inflammatory effects. The document also outlines prostaglandin nomenclature and biosynthesis.
This document describes a study that synthesized novel 2,3-dihydro-1H-inden-1-one chalcone-like compounds and their hydroxyl derivatives to evaluate their inhibitory effects on mushroom tyrosinase activity. Two compounds, 2a and 2b, inhibited tyrosinase's diphenolase activity in a dose-dependent manner, with IC50 values lower than the positive control, kojic acid. Kinetic analysis showed that compounds 2a and 2b are reversible competitive inhibitors of tyrosinase. Compound 2b, with a 3,4-dihydroxy group resembling the substrate L-DOPA, exhibited the most potent inhibition, suggesting hydroxy-substituted 2,
This study synthesized and characterized Schiff base transition metal complexes of cobalt(II) and copper(II) acetylacetonate (acac) ligands. The cobalt(II) and copper(II) acac complexes were tested for their antimicrobial properties against bacteria and fungi. Both complexes showed little to no inhibitory effects on the microbes tested. Their structures were characterized through UV-Vis spectroscopy, which identified maximum absorbances of 491 nm for cobalt(II) acac and 632 nm for copper(II) acac.
In-vitro biological activities of the free new H4L ( indole-7-thiocarbohydrazone) ligand and its Ni(II), Pd(II) , Pt(II),
Cu(II), Ag(I), Zn(II) and Cd(II) complexes are screened against two cancerous cell lines, that revealed significant
activity only for [Cu2Cl2(H4L)2(PPh3)2] after 72 h treatment by the highest tested concentrations. The Copper(I)
complex was characterized by X-ray Crystallography and the NMR spectra, whereas it has been confirmed to have
momentous cytotoxicity against ovarian, breast cancerous cell lines (Caov-3, MCF-7). The apoptosis-inducing
properties of the Cu(I) complex have been investigated through fluorescence microscopy visualization, DNA
fragmentation analysis and propidium iodide flow cytometry.
Anticancer Activity of New Di-Nuclear Copper (I) ComplexTaghreed Al-Noor
In-vitro biological activities of the free new H4L ( indole-7-thiocarbohydrazone) ligand and its Ni(II), Pd(II) , Pt(II),
Cu(II), Ag(I), Zn(II) and Cd(II) complexes are screened against two cancerous cell lines, that revealed significant
activity only for [Cu2Cl2(H4L)2(PPh3)2] after 72 h treatment by the highest tested concentrations. The Copper(I)
complex was characterized by X-ray Crystallography and the NMR spectra, whereas it has been confirmed to have
momentous cytotoxicity against ovarian, breast cancerous cell lines (Caov-3, MCF-7). The apoptosis-inducing
properties of the Cu(I) complex have been investigated through fluorescence microscopy visualization, DNA
fragmentation analysis and propidium iodide flow cytometry.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, 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.
This document summarizes recent research on using gold nanoclusters (Au NCs) for biomedical applications. It discusses how Au NCs that are less than 6 nm in size can be cleared renally due to their ultra-small size. Their tunable photoluminescence from UV to near-infrared makes them suitable for multimodal imaging. The document reviews methods for synthesizing different types of Au NCs stabilized by various ligands and discusses parameters that influence their behavior after administration in small animals. It presents recent advances in using Au NCs as theranostic agents and compares them to other contrast agents.
During favorable conditions, the level of reactive spices in the cell is limited to what is required for normal cellular activities. They act as important components of signaling pathways. Plants control some important processes such as defense, hormonal signaling and development by using them as signaling molecules. And An equilibrium is steblished between antioxidant system and ros formation. But when plant feels an external stress like, drought,cold, salt etc. the level of reactive specease increases above the basal level a situation that we call oxidative stress. These reactive molecules during oxidative stress, they react with biomolecules like as carbohydrates, unsaturated lipids, proteins, nucleic acids. Proteins are the most abundant cellular targets of the oxidative species, more than DNA and lipids, making up 68% of the oxidized molecules in the cell. Ros reacts with proteins which results in protein modification called redox PTMs.
This document summarizes the synthesis and characterization of lanthanide complexes with the drug cloxacillin. Cloxacillin is an antibiotic drug that is commonly used to treat bacterial infections. Seven lanthanide complexes of the form [Ln(Clox)2(H2O)2]Cl where Ln = La(III), Pr(III), Nd(III), Sm(III), Dy(III), Ho(III) and Er(III) were synthesized. The complexes were characterized using elemental analysis, infrared spectroscopy, electronic spectroscopy, magnetic susceptibility measurements, and thermal analysis. Elemental analysis showed a 1:2 metal to ligand ratio in the complexes. Infrared spectroscopy indicated that cloxacillin binds in
Synthesis, characterization, amdet and docking studies of novel diclofenac de...Alexander Decker
This document discusses the synthesis and characterization of novel diclofenac derivatives containing phenylalanine moieties as selective inhibitors of cyclooxygenase-2 (COX-2). Sixteen novel diclofenac derivatives were synthesized and their structures were confirmed through various analytical techniques. Molecular docking studies predicted that compounds 7, 12 and 16 showed stronger binding with COX-2 than the reference drug diclofenac, making them potential selective COX-2 inhibitors. The binding scores of these compounds were higher than diclofenac when docked into the active site of COX-2.
Detailed characterization of saponins isolated from Zygophyllum Propinqueem D...Open Access Research Paper
Zygophyllum propinquum Decne (syn. Z. coccineum, family: Zygophyllaceae) is a low shrub, perennial herb, or desert succulent undershrub and has several important biological activities. The major secondary metabolites of this plant are a class of ursane-type triterpene saponins. Saponins derive their name from stable foam formation in water. These saponins have peculiar properties like, bitterness, fish poisoning, haemolysis, complex formation with cholesterol. Saponins are consisting of two main parts, one is the aglycone part while the other one is the glycone part. The glycone part is further consisting of sugar moieties. Current studies were conducted to isolate specifically biologically important saponins. Saponins were isolated successfully using standard procedures and characterized successfully using different spectroscopic techniques including Fourier Transform-Infrared Spectroscopy, Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy. Two saponins were isolated from the whole plant of Zygophyllum propinquum Decne with the help of repeated column chromatography and HPLC. The purified saponins were hydrolyzed with H2SO4-dioxane resulting in lactone formation. All the compounds (saponins and lactone) were characterized with the help of FAB-MS and 1D and 2D-NMR techniques. Their structures were confirmed to be 3-O–β-D-glucopyranosyl-(1→6)- β-D-2-O-sulfo-glucuronopyranosylurs-20(21)-en28 oic acid 28-O-[β-D-glucuronopyranosyl] ester (1), (3β–O-2-O-sulfo-β-D-glucuronopyranosylurs-20(21)-en28 oic acid 28-O-[β-D-2-O-sulfonylglucuronopyranosyl] ester (2), and 3β-Hydroxy urs-28,20 β-olide (3).
This study synthesized a series of hydroxy-substituted chalcone oxime derivatives and evaluated their inhibitory effects on tyrosinase and melanin formation in mouse melanoma cells. Two compounds exhibited much stronger tyrosinase inhibition than the positive control kojic acid. Kinetic studies showed that these compounds act as competitive tyrosinase inhibitors by binding to the enzyme's active site. Both compounds inhibited tyrosinase activity and melanin production in mouse melanoma cells, suggesting their potential as skin lightening agents.
This document discusses a study on the inhibitive properties and quantum chemical analysis of 1,4-benzothiazine derivatives for corrosion inhibition of mild steel in acidic medium. Two derivatives, compounds P3 and P4, were synthesized and their structures were confirmed through various analytical techniques. Electrochemical tests including polarization, electrochemical impedance spectroscopy, and weight loss measurements were used to evaluate the corrosion inhibition efficiency of P3 and P4 in 1 M HCl solution. Quantum chemical calculations based on density functional theory were also performed to correlate inhibition efficiency with molecular properties. The results showed that P3 and P4 acted as efficient corrosion inhibitors for mild steel in acidic solution, with inhibition efficiency increasing with increasing concentration. Adsorption
This document discusses an enzyme called cyclooxygenase. Prostaglandin Endoperoxide H Synthase (Commonly known as "Cyclooxygenase") is an enzyme essential for immune response and mainly, in prostaglandin biosynthesis (a metabolic pathway in Arachidonic acid metabolism). Read the document for further information.
SiO2@FeSO4 nano composite: A recoverable nano-catalyst for eco-friendly synth...Iranian Chemical Society
Various aldoximes and ketoximes synthesis of corresponding aldehydes and ketones in the presence of SiO2@FeSO4 nano composite as recoverable nano catalyst and NH2OH·HCl. The SiO2@FeSO4 nano composite system was carried out between 10 to 15 min in oil bath (70-80 °C) under solvent-free condition in excellent yields in addition this protocol can be used for industrial scales. This method offers some advantages in term of clean reaction conditions, easy work-up procedure, short reaction time, applied to convert α-diketones to α-diketoximes (as longer than other carbonyl compounds), α,β-unsaturated aldehydes and ketones to corresponding oximes and suppression of any side product. So we think that NH2OH•HCl/SiO2@FeSO4 nano composite system could be considered a new and useful addition to the present methodologies in this area. Structure of products and nano composite elucidation was carried out by 1H NMR, 13C NMR, FT-IR, scanning electron microscopy (SEM).
Organomercury compounds have a variety of applications despite their toxicity. This document discusses two recent research topics on the use of organomercury catalysts:
1) The development of organomercury haptens for enzyme-linked immunoassays to detect inorganic and organic mercury. Antibodies were successfully generated that could bind both mercury ions and organometallic forms of mercury.
2) A direct method for derivatizing disulfide bonds in proteins using organic mercury in alkaline medium without chemical pre-reducing agents. p-Hydroxymercurybenzoate was shown to effectively label disulfide groups in lysozyme, allowing for their one-step determination.
Overall, the document
1. krebs cycle activators, inhibitors and their roles in the modulation of ...kennyfranz1
The document discusses the Krebs cycle, which is a series of chemical reactions in mitochondria that breaks down nutrients to generate energy. It focuses on how the cycle produces molecules like NADH that fuel ATP production and provides reducing power to cells. The review examines the Krebs cycle pathways, key enzymes and reactions involved, and how activators and inhibitors can impact energy metabolism and carcinogenesis.
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3. Introduction
• Over the last 100 years, nonsteroidal anti-inflammatory drugs (NSAIDs)
were among the most prominent and frequently used drugs in medicine
for the treatment of pain, fever, inflammation and arthritis-associated
disorders.
• The main therapeutic mechanism of NSAIDs action involves inhibition of
cyclooxygenase-mediated biosynthesis of prostaglandins (PGs).
• Cyclooxygenase (prostaglandin endoperoxide synthase or COX) enzyme
exists in at least two closely related isoforms1–4 viz. COX-1 and COX-
2. COX-1 is consecutively expressed in most tissues.
• COX-1 is involved in homeostasis of cytoprotective PGs in the
gastrointestinal tract, homeostasis of proaggregatory thromboxane A2
(TXA2) in blood platelets and in overall vascular homeostasis.
4. • In contrast, inducible COX-2 isoform is absent in most organs and
tissues, except for brain, kidney, pancreas, uterus, ovary, and
macrophages.
• However, upon inflammatory or carcinogenic stimulation, COX-2
expression levels are elevated, and COX-2 is responsible for the
production of inflammatory PGs.
• Moreover, high levels of COX-2 were also found in various human
cancers like gastric, breast, lung, colon, oesophageal, prostate, and
hepatocellular carcinomas.
• Classical NSAIDs (aspirin, ibuprofen, meclofenamic acid and
indomethacin) block the activity of both COX isoforms non-selectively
to exhibit their anti-inflammatory effects, which leads to unwanted side
effects by the inhibition of COX-1
5.
6. • Inhibition of consecutively expressed COX-1 isoform and/or downfall in
the production of physiological PGs by classical NSAIDs is considered
as the basis of life-threatening side effects such as gastrointestinal
irritation, ulcer, hepatic and renal toxicity.
• In this context, selective inhibition of COX-2 was proposed to be a safer
therapeutical approach to reduce deleterious side effects of classical
NSAIDs.
• As a result, a variety of selective COX-2 inhibitors (COXIBs) such as
celecoxib (1), rofecoxib (2), valdecoxib (3), etoricoxib (4) and lumiracoxib
(5) have been developed (fig1)
7. • Selective COX-2 inhibitors have widely been used for the
treatment of inflammation and a variety of diseases such as
rheumatoid arthritis, osteoarthritis, Alzheimer’s disease (AD) and
Parkinson’s disease.
• Besides these therapeutic applications, NSAIDs have also been
found to play an important role in the prevention of several types
of human cancer such as colon, lung, breast and prostate
cancers.
• Over the last two decades, numerous studies have been
carried out to improve the COX-2 selectivity and safety profile.
8. • However, various selective COX-2 inhibitors came under scrutiny
due to an increased risk of adverse cardiovascular side effects.
• This development led to the withdrawal of rofecoxib and
valdecoxib from the market and stimulated the development of
novel classes of selective and safe COX-2 inhibitors with reduced
cardiovascular side effects.
• In this line, several nitric oxide releasing NSAIDs and dual
COX/LOX inhibitors have been developed recently.
9. • Among the different classes of COXIBs, several vicinal diaryl
heterocycles bearing a p-methylsulfonyl- or p-aminosulfonyl-aryl
substituent rings represent the most important class of selective COX-
2 inhibitors.
• Structure–activity relationship (SAR) data indicate that the nature and
position of substituents on two vicinal aryl rings is an important
determinant.
• It has been observed that compounds containing RSO2 (R = NH2, CH3,)
groups effectively interact with amino acid residues of the COX-2
secondary pocket resulting in a generally high COX-2 selectivity and
potency profile.
• Recently, our group has reported the synthesis of various 1,4 and 1,5-
diaryl substituted 1,2,3-triazoles (6–11, Fig. 1) as COX-2 inhibitors.
• .
10.
11. • From this study it was concluded that compounds containing a vicinal
diaryl substitution pattern display higher COX-2 inhibition potency
compared to their corresponding 1,4- diaryl-substituted counterparts.
Both series of compounds showed moderate COX-2 selectivity profiles.
• As an extension to this work, we now describe the synthesis of a novel
class of 1,4 diaryl-substituted triazoles as potential selective COX-2
inhibitors.
• Novel compounds were designed based on Cu(I)-mediated click
chemistry between azides containing the SO2NH2 COX-2
pharmacophore attached to an aryl ring and various aryl acetylenes
containing different substitutents (H, F, Cl, CH3 or OCH3) attached to
the para position of the aryl ring
12. • . Furthermore, the size of the molecule was increased through the
introduction of an alkyl linker to enhance flexibility of the compound to
facilitate COX-2 binding. The COX-1/COX-2 inhibitory activities of
these compounds were determined in a COX binding assay, and
plausible binding interactions within the COX-1/COX-2 active sites
were explored using molecular docking studies
13. Chemistry
There is three categories of compounds which is 1,4
-
elozairt detutitsbuslyraid
:
1. Category 14
_
18
2. Category 21
_
25
3. Category 28
_
32
They are all di substituted triazole but they have a linker
(n= 0,1,2
HC,lC,F,H=R dna (
3
HCO,
3
All contain triazole ring as the name implies and two aromatic
rings.
15. Point of view
To discuss the effect of chain length, size and flexibility of the
molecule on the COX- 1
XOC/
-
2 inhibitory potency and selectivity
(SI).
The chemical approach used here is popular click chemistry Cu+
mediated [ 2+3
ediza citamora eerht fo noitcaer noitiddaolcyc ]
) erutcurts enelyteca lyra detutitsbus suoirav htiw
4
-
, H
4
-
,F
4
-
,lC
4
-
HC
3,4
-
HCO
3
ekam ot (
1,4
-
elozairt detutitsbus lyraid
.
Equimolar amount are used in precence of ETOH/H2O ,Cu+and
triethylamine at 60
°
rof C
14
_
16 hour.
Moderate to good chemical yeild 54
_
89% after purification.
18. • The COX-1/2 inhibitory potency and selectivity profile of
compounds 14
–
18
,
21
–
25
dna ,
28
–
32 was determined in
triplicate using a fluorescent COX- 1
XOC/
-
2 inhibitor screening
assay kit.
• In vitro study showed that all classes exhibit potency on COX-
2 over COX-1.
• Range of IC50 of COX-2 = 0.17-28 Mm
• Range of IC50 of COX-1 = 21 to >100 mM
19. • Synthesis of compounds 14, 15, 17 and 18 as
potential inhibitors of carbonic anhydrases VA and
VB was reported recently.
20. Category I (14-18)
N=0 R=H,F,Cl,CH3,OCH3
Para-phenyl sulfonamide attached directly to
N-1 of the triazole ring.
24. • MOST POTENT and SELECTIVE inhibitor of COX-2 .
• COX-1 IC50 = > 100mM.
• COX-2 IC50 = 1.2mM.
• SI = 83
25. • displayed comparable COX-2 inhibitory potency but COX-2
selectivity index of compound 22 was smaller than that of
compound 24.
• COX-2 IC50 = 1.5mM.
• SI = 13.3
26. Category III )
32
-
28
(
• N=2, R=H,F,Cl,CH3,OCH3
Compound 30 the most potent cox-2
inhibitor.
• COX-2 IC50 = 0.17mM.
•SI = >588
28. • COX-1 IC50 = >100mM.
• COX-2 IC50 = 1mM.
Compounds 28,29 have low potency toward cox-
2 but high cox-2 selectivity.
29.
30. What can be used as lead
compound ?
The most effective compound is 30 because it
display high potency and selectivity.
So it can be a lead compound.
32. Molecular modeling (docking) studies were carried out for compounds
(16, 23, 30) to gain more insights into the probable nature of their
respective binding interactions within the active site of COX-1 and COX-2
isozymes. Docking experiments were performed using X-ray crystal
structure data for COX-1 and COX-2 obtained from the protein data bank.
33. Compound 16, when docked into the COX-2 binding site , comfortably
enters into the COX-2 active site and places its para-Cl-phenyl
substituent near S530, L531residues, while one of the nitrogen atom of the
triazole ring indicates hydrogen bonding interactions with V523 residue of
COX-2 active site (NO = 1.55 Å). The SO2NH2 group as prominent and
effective COX-2 pharmacophore) is pointed near the COX-2 isozyme
secondary pocket amino acid residues (A516, F518, R513, Q192 and H90).
34. In a comparable manner, compound 23 displays a favorable orientation in
the COX-2 active site and the SO2NH2 group is oriented at the entrance
of the secondary pocket. This places the SO2NH2 group near the R513,
L352 residues. The 4-chlorophenyl substituent was moved near to the
L359 amino acid of the COX-2 binding site.
35. A similar molecular docking simulation for compound 30 within the COX-2
active site, showed noticeable interactions between compound 30 and active
binding site residues .The SO2NH2 group in compound 30 deeply enters into
the secondary pocket region of the COX-2 active site, where it is oriented
towards Q192, R513, H90, and S353 residues. The nitrogen atom of the
SO2NH2 group indicates hydrogen bonding interactions with the oxygen of
carbonyl group of Q192 ,and one of the oxygen atom of SO2NH2 group is
hydrogen bonded to the nitrogen atom of H90 residue.
36. However, in contrast to binding interactions of compound 16
and 23, the docking results of compound 30 indicate that upon
increasing the size of the linker chain (n = 2), there is an
increase in the flexibility of the molecule which facilitates the
deeper insertion of the SO2NH2 group into the secondary binding
pocket and more significant intermolecular binding interactions.
This favorable orientation and electrostatic binding interactions of
compound 30 with COX-2 active site residues are consistent
with experimentally observed high COX-2 inhibitory potency
(COX-2 IC50 = 0.17 lM). A comparison of the binding mode of
compounds 16, 23 and 30 in the COX-2 active site using a
molecular docking structure containing all three compounds (16,
23 and 30) docked in the same COX-2 active site is given in the
Supplementary section.
37. Alternatively, docking results for compound 16, 23 and 30 in
COX-1 active site show that compound 16 comfortably enters
into the COX-1 active site and its p-Cl-phenyl substituent has
moved into the hydrophobic subpocket of COX-1isozyme
constituted by W387, Y385 and F381 residues.
38. However, during docking studies of compound 23 and 30 into
COX-1, compounds were not able to enter into the COX-1 active
site completely .This inability is likely due to the increase in their
size or/and due to the steric conflict with side chains of amino acid
residues of the active site. This body of data evidently supports the
experimentally observed weak COX-1inhibitory activity of
compound 23 and 30.
23 30
39. Conclusions
In conclusion, a new class of 1,4-diaryl-substituted triazoles was
synthesized using high yielding Cu(I)-mediated click chemistry. In vitro
COX-1/COX-2 inhibition studies showed that some compounds of this
novel class of 1,4-diaryl-substituted triazoles are able to inhibit COX-2
with high otency and selectivity. Especially compounds (28–30) were
identified as highly potent (IC50 range 0.17–1.1Mm) and selective novel
COX-2 inhibitors (SI >91 to >588). Among all investigated compounds, a
‘lead compound’ 4-{2-[4-(4-Chloro-phenyl)-[1,2,3]triazol-1-yl]-ethyl}-
benzenesulfon-amide was identified that exhibited appreciable COX-2
inhibitory potency and selectivity (COX-1 IC50 >100 lM, COX-2 IC50 =
0.17 lM; SI >588).
40. Molecular docking analyses for compounds 16, 23 and 30 on the
COX-1/COX-2 isozymes complement the experimental results. From
both the experimental structure– activity data and the molecular
docking results it can be concluded that an increase of the length of
the linker chain is accompanied with an enhancement in molecular
interactions between functional groups of the compounds and amino
acid residues of the secondary pocket of the COX-2 active site.