Novel Hybrid Molecules of Quinazoline Chalcone Derivatives: Synthesis and Stu...Ratnakaram Venkata Nadh
Abstract: Background: A new series of quinazoline linked chalcone conjugates were synthesized
and evaluated for their in vitro cytotoxicity.
Methods: The quinazoline-chalcone derivatives (13a-r) have been prepared by the Claisen-Schmidt
condensation of various substituted benzaldehydes (12a-r) with substituted l-(4-(3,4-
dihydroquinazolin-4-ylamino)phenyl)ethanone (11a-b) in the presence of aqueous NaOH. Three
potential compounds 13f, 13g and 13h exhibited cytotoxicity against leukemia (GI50 value of
1.07, 0.26 and 0.24 μM), Non-small lung (GI50 values of 2.05,1.32 and 0.23 μM), colon (GI50
values of 0.54, 0.34 and 0.34 μM) and breast (GI50 values of 2.17, 1.84 and 0.22 μM) cell line,
respectively.
Results and Conclusion: Based on these biological results, it is evident that compound 13h has the
potential to be considered for further detailed studies either alone or in combination with existing
therapies as potential anticancer agents.
QSAR Modeling of Bisbenzofuran Compounds using 2D-Descriptors as Antimalarial...ijtsrd
In the present study we have performed Quantitative structure activity relationship (QSAR) analysis for 43bisbenzofuran derivatives to estimate the antimalarial activity using some 2D descriptors. Several significant QSAR models has been calculated for predicting the antimalarial activity (“logIC50) of these molecules by using the multiple linear regression (MLR) technique. Among the obtained QSAR models, a four parametric model was most significant having R2=0.9502. An external set was used for confirming the predictive power of the models. High correlation between experimental and predicted antimalarial activity values, was obtained in the validation approach that displayed the good modality of the derived QSAR models. Tripti Kaushal | Anita K | Bashirulla Shaik | Vijay K. Agrawal"QSAR Modeling of Bisbenzofuran Compounds using 2D-Descriptors as Antimalarial Agents" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-2 , February 2018, URL: http://www.ijtsrd.com/papers/ijtsrd9497.pdf http://www.ijtsrd.com/chemistry/other/9497/qsar-modeling-of-bisbenzofuran-compounds-using-2d-descriptors-as-antimalarial-agents/tripti-kaushal
Predictive comparative qsar analysis of as 5 nitrofuran-2-yl derivatives myco...hiij
Antitubercular activity of 5-nitrofuran-2-yl Deriva
tives series were subjected to Quantitative Struc
ture
Activity Relationship (QSAR) Analysis with an effo
rt to derive and understand a correlation between t
he
biological activity as response variable and differ
ent molecular descriptors as independent variables.
QSAR models are built using 40 molecular descriptor
dataset. Different statistical regression express
ions
were got using Partial Least Squares (PLS) ,Multip
le Linear Regression (MLR) and Principal Component
Regression (PCR) techniques. The among these techni
que, Partial Least Square Regression (PLS)
technique has shown very promising result as compar
ed to MLR technique A QSAR model was build by a
training set of 30 molecules with correlation coe
fficient (
) of 0.8484 , significant cross validated
correlation coefficient (
) is 0.0939,
is 48.5187,
for external test set (
_
)
is -0.5604,
coefficient of correlation of predicted data set
( _
) is 0.7252 and degree of freedom is 26 by
Partial Least Squares Regression technique.
Novel Hybrid Molecules of Quinazoline Chalcone Derivatives: Synthesis and Stu...Ratnakaram Venkata Nadh
Abstract: Background: A new series of quinazoline linked chalcone conjugates were synthesized
and evaluated for their in vitro cytotoxicity.
Methods: The quinazoline-chalcone derivatives (13a-r) have been prepared by the Claisen-Schmidt
condensation of various substituted benzaldehydes (12a-r) with substituted l-(4-(3,4-
dihydroquinazolin-4-ylamino)phenyl)ethanone (11a-b) in the presence of aqueous NaOH. Three
potential compounds 13f, 13g and 13h exhibited cytotoxicity against leukemia (GI50 value of
1.07, 0.26 and 0.24 μM), Non-small lung (GI50 values of 2.05,1.32 and 0.23 μM), colon (GI50
values of 0.54, 0.34 and 0.34 μM) and breast (GI50 values of 2.17, 1.84 and 0.22 μM) cell line,
respectively.
Results and Conclusion: Based on these biological results, it is evident that compound 13h has the
potential to be considered for further detailed studies either alone or in combination with existing
therapies as potential anticancer agents.
QSAR Modeling of Bisbenzofuran Compounds using 2D-Descriptors as Antimalarial...ijtsrd
In the present study we have performed Quantitative structure activity relationship (QSAR) analysis for 43bisbenzofuran derivatives to estimate the antimalarial activity using some 2D descriptors. Several significant QSAR models has been calculated for predicting the antimalarial activity (“logIC50) of these molecules by using the multiple linear regression (MLR) technique. Among the obtained QSAR models, a four parametric model was most significant having R2=0.9502. An external set was used for confirming the predictive power of the models. High correlation between experimental and predicted antimalarial activity values, was obtained in the validation approach that displayed the good modality of the derived QSAR models. Tripti Kaushal | Anita K | Bashirulla Shaik | Vijay K. Agrawal"QSAR Modeling of Bisbenzofuran Compounds using 2D-Descriptors as Antimalarial Agents" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-2 , February 2018, URL: http://www.ijtsrd.com/papers/ijtsrd9497.pdf http://www.ijtsrd.com/chemistry/other/9497/qsar-modeling-of-bisbenzofuran-compounds-using-2d-descriptors-as-antimalarial-agents/tripti-kaushal
Predictive comparative qsar analysis of as 5 nitrofuran-2-yl derivatives myco...hiij
Antitubercular activity of 5-nitrofuran-2-yl Deriva
tives series were subjected to Quantitative Struc
ture
Activity Relationship (QSAR) Analysis with an effo
rt to derive and understand a correlation between t
he
biological activity as response variable and differ
ent molecular descriptors as independent variables.
QSAR models are built using 40 molecular descriptor
dataset. Different statistical regression express
ions
were got using Partial Least Squares (PLS) ,Multip
le Linear Regression (MLR) and Principal Component
Regression (PCR) techniques. The among these techni
que, Partial Least Square Regression (PLS)
technique has shown very promising result as compar
ed to MLR technique A QSAR model was build by a
training set of 30 molecules with correlation coe
fficient (
) of 0.8484 , significant cross validated
correlation coefficient (
) is 0.0939,
is 48.5187,
for external test set (
_
)
is -0.5604,
coefficient of correlation of predicted data set
( _
) is 0.7252 and degree of freedom is 26 by
Partial Least Squares Regression technique.
Pharmacophore modeling: A continuously evolving tool for computational drug d...Simone Brogi
In the latest two or three years progressive
applications of pharmacophore modeling continue to appear in literature. Pharmacophore based parallel screening, for instance, has been introduced in 2006. Moreover, in 2008, a survey discussing the prospective impact of virtual screening techniques in the
discovery of bioactive natural products has been published.
Sulfentrazone and Flumetsulam herbicides caused DNA damage and Instability in...Agriculture Journal IJOEAR
Abstract— Boral 500® (sulfentrazone as active ingredient) and Scorpion® (flumetsulam as active ingredient) are herbicides widely used in Brazil´s soybean crops. U.S. Environmental Protection Agency classificated them as non-carcinogenic and no mutagenic, but literature shows that often this classification is misguided. Allium cepa assay was chosen to evaluate these herbicides, once it analyzes the frequency of micronuclei (MN), chromosomal aberrations (CA) and the mitotic index (MI). Four concentrations of each herbicide (50, 75, 100 and 125 %) were tested in triplicate using distilled water (negative control) and methyl methanesulfonate (positive control) as controls. Three experimental repetitions were realized. Boral 500® showed a higher MI in all concentrations, and higher CA and MN in the 75%, 100% and 125% concentration, with no recovery. Scorpion® showed a higher MI, CA and MN in 100% and 125% concentration, with recovery only for MI and CA. Both herbicides showed mutagenic damage and increased proliferative capacity in Allium cepa. So on, these herbicides should be revaluated as mutagenicity and carcinogenicity for responsible agencies.
Novel Hybrid Molecules of Isoxazole Chalcone Derivatives: Synthesis and Study...Ratnakaram Venkata Nadh
medicine due to their significant role in the treatment of different health problems.
Methods: We have synthesized new series of isoxazole-chalcone conjugates (14a-m) by the
Claisen-Schmidt condensation of suitable substituted acetophenones with isoxazole aldehydes (12a-d).
In vitro cytotoxic activity of the synthesized compounds was studied against four different selected
human cancer cell lines by using sulforhodamine B (SRB) method.
Results: The adopted scheme resulted in good yields of new series of isoxazole-chalcone
conjugates (14a-m). Potent cytotoxic activity was observed for compounds -14a, 14b, 14e, 14i, 14j
and 14k against prostate DU-145 cancer cell line.
Conclusion: The observed potent cytotoxic activities were due to the presence of 3,4,5-
trimethoxyphenyl group.
Pharmacophore modeling: A continuously evolving tool for computational drug d...Simone Brogi
In the latest two or three years progressive
applications of pharmacophore modeling continue to appear in literature. Pharmacophore based parallel screening, for instance, has been introduced in 2006. Moreover, in 2008, a survey discussing the prospective impact of virtual screening techniques in the
discovery of bioactive natural products has been published.
Sulfentrazone and Flumetsulam herbicides caused DNA damage and Instability in...Agriculture Journal IJOEAR
Abstract— Boral 500® (sulfentrazone as active ingredient) and Scorpion® (flumetsulam as active ingredient) are herbicides widely used in Brazil´s soybean crops. U.S. Environmental Protection Agency classificated them as non-carcinogenic and no mutagenic, but literature shows that often this classification is misguided. Allium cepa assay was chosen to evaluate these herbicides, once it analyzes the frequency of micronuclei (MN), chromosomal aberrations (CA) and the mitotic index (MI). Four concentrations of each herbicide (50, 75, 100 and 125 %) were tested in triplicate using distilled water (negative control) and methyl methanesulfonate (positive control) as controls. Three experimental repetitions were realized. Boral 500® showed a higher MI in all concentrations, and higher CA and MN in the 75%, 100% and 125% concentration, with no recovery. Scorpion® showed a higher MI, CA and MN in 100% and 125% concentration, with recovery only for MI and CA. Both herbicides showed mutagenic damage and increased proliferative capacity in Allium cepa. So on, these herbicides should be revaluated as mutagenicity and carcinogenicity for responsible agencies.
Novel Hybrid Molecules of Isoxazole Chalcone Derivatives: Synthesis and Study...Ratnakaram Venkata Nadh
medicine due to their significant role in the treatment of different health problems.
Methods: We have synthesized new series of isoxazole-chalcone conjugates (14a-m) by the
Claisen-Schmidt condensation of suitable substituted acetophenones with isoxazole aldehydes (12a-d).
In vitro cytotoxic activity of the synthesized compounds was studied against four different selected
human cancer cell lines by using sulforhodamine B (SRB) method.
Results: The adopted scheme resulted in good yields of new series of isoxazole-chalcone
conjugates (14a-m). Potent cytotoxic activity was observed for compounds -14a, 14b, 14e, 14i, 14j
and 14k against prostate DU-145 cancer cell line.
Conclusion: The observed potent cytotoxic activities were due to the presence of 3,4,5-
trimethoxyphenyl group.
GQSAR is a breakthrough patent pending methodology that significantly enhances the use of QSAR as an approach for new molecule design. As a predictive tool for activity, this method is significantly superior to conventional 3D and 2D QSAR. Here we explain application of GQSAR for optimizing compounds in congeneric series.
The importance of data curation on QSAR Modeling: PHYSPROP open data as a cas...Kamel Mansouri
This presentation highlighted how data curation impacts the reliability of QSAR models. We examined key datasets related to environmental endpoints to validate across chemical structure representations (e.g., mol file and SMILES) and identifiers (chemical names and registry numbers), and approaches to standardize data into QSAR-ready formats prior to modeling procedures. This allowed us to quantify and segregate data into quality categories. This improved our ability to evaluate the resulting models that can be developed from these data slices, and to quantify to what extent efforts developing high-quality datasets have the expected pay-off in terms of predicting performance. The most accurate models that we build will be accessible via our public-facing platform and will be used for screening and prioritizing chemicals for further testing.
Synthesis & Pharmacological Activity of Cytotoxicity Assay of Coumarins SVCM1...AI Publications
The therapeutic properties of natural and synthetic compounds against human illnesses have attracted a lot of interest. The pharmacological and biological effects of coumarins are widely exploited in medicine; they include anti-inflammatory, anticoagulant, antihypertensive, anticonvulsant, antioxidant, antibacterial, and neuroprotective properties. Signaling pathways affecting many cellular functions may also be modulated by coumarin derivates. Whether or not a coumarin has pharmacological, biochemical, or therapeutic characteristics is dependent on the nature of the replacement surrounding the coumarin core structure. The capacity to kill, repel, or otherwise impact the development of Anopheles arabiensis mosquitoes was evaluated using seven synthetic halogenated coumarins (SVCM1-SVCM7). The compounds SVCM1-SVCM7 were evaluated for their bactericidal and fungicidal activities using the disc diffusion method.
Allometry Scalling in Drug Development by Murugesh Kandasamy in Advancements in Bioequivalence & Bioavailability
Allometry is about the study of body size and its outcomes, it is described as ‘by a different measure’, and in allometric system the proportions are changed in a regular fashion [1]. Allometry, which is the oldest of the approaches and still widely applied in biology, is concerned with the study of the relationship between the size and function of components of the body and growth or size of the whole body [2]. Alternatively, to study the species change in a specific factor which correlates with difference in size of the species. Allometry is centered on the prediction (an exact prediction) by considering the physiological, anatomical and biochemical parallels among animals, which can be explained by mathematical models. It is now an established fact that many physiological processes and size of the organ that exhibit a power-law relationship with the body weight of the species. This relationship is defined as the scientific source of allometric scaling [3,4].
https://crimsonpublishers.com/abb/fulltext/ABB.000512.php
Each and every biological function in living organism occurs due to protein-protein interactions. The
diseases are no exception to this. Identifying one or more proteins for a particular disease and then
designing a suitable chemical compound (which is known as drug or ligand) to destroy those proteins is a
challenging topic of research in computational biology. In earlier methods, drugs were designed using only
a few chemical components and were represented as a fixed-length tree. But in reality, a drug contains
many chemical groups collectively known as pharmacophore. Moreover, the chemical length of the drug
cannot be determined before designing that drug.
In the present work, a Particle Swarm Optimization (PSO) based methodology has been proposed to find
out a suitable drug for a particular disease so that the drug-target protein interaction energy becomes
minimum. In the proposed algorithm, the drug is represented as a variable length tree and essential
functional groups are arranged in different positions of that drug. Finally, the structure of the drug is
obtained and its docking energy is minimized simultaneously. Also, the orientation of chemical groups in
the drug is tested so that it can bind to a particular active site of a target protein and the drug fits well
inside the active site of target protein. Here, several inter-molecular forces have been considered for
accuracy of the docking energy. Results are demonstrated for three different target proteins both
numerically and pictorially. Results show that PSO performs better than the earlier methods.
Study on multi-target mechanism of Radix et Rhizoma Rhei (Dahuang) and Semen ...LucyPi1
Abstract Objective: To explore the mechanism of action of Radix et Rhizoma Rhei (Dahuang) (RERR) and Semen Persicae (Taoren) (SP) on adhesive intestinal obstruction (AIO). Methods: The main targets of the active ingredients of RERR and SP were filtered based on the traditional Chinese medicine system pharmacology analysis platform. Cytoscape 3.2.1 was applied to build the ingredient-target network of RERR and SP for AIO. Results: Fifteen active components were predicted from the RERR and SP herb pair, such as aloe-emodin, catechin, rhein, gibberellin (GA) 119, GA120 and GA121. These components were applied to 59 targets mainly involved in many biological processes such as signal transduction, anti-apoptosis, and inflammatory response involved in activating the immune effect. Conclusion: This study proposes the system pharmacology method and identifies the potent combination therapeutic mechanism of RERR and SP for AIO. This strategy will provide a new insight to the study of herb combinations.
B. PHARM 6TH SEMESTER DRUG DESIGN. FACTORS, QSAR, DRUG DISCOVERY, DRUG DEVELOPMENT, VARIOUS APPROACHES FOR DRUG DESIGN, PARTITION COEFFICIENT, HAMMETS EQUATION, TAFTS STERIC PARAMETER, HANSCH ANALYSIS
QSAR Studies of the Inhibitory Activity of a Series of Substituted Indole and...inventionjournals
HF method, with the basis set 6-31G (d) was employed to calculate quantum some chemical descriptors of 37 substituted Indole. The best descriptors were selected to establish the quantitative structure activity relationship (QSAR) of the inhibitory activity against isoprenylcysteine carboxyl methyltransferase (Icmt), by principal components analysis (PCA), to a multiple regression analysis (MLR), to a nonlinear regression (RNLM) and to an artificial neural network (ANN). We accordingly propose a quantitative model and we interpret the activity of the compounds relying on the multivariate statistical analysis. This study shows that the MLR and have served to predict activity, but when compared with the results given by the ANN model. We concluded that the predictions achieved by this latter is more effective and much better than other models. The statistical results indicate that the model is statistically significant and shows very good stability towards data variation in the validation method. The contribution of each descriptor to the structure-activity relationship is evaluated.
Predicting active compounds for lung cancer based on quantitative structure-a...IJECEIAES
Recently, advancements in computational and artificial intelligence (AI) methods have contributed in improving research results in the field of drug discovery. In fact, machine learning techniques have proven to be especially effective in this regard, aiding in the development of new drug variants and enabling more precise targeting of specific disease mechanisms. In this paper, we propose to use a quantitative structure-activity relationship-based approach for predicting active compounds related to non-small cell lung cancer. Our approach uses a neural network classifier that learns from sequential structures and chemical properties of molecules, as well as a gradient boosting tree classifier to conduct comparative analysis. To evaluate the contribution of each feature, we employ Shapley additive explanations (SHAP) summary plots to perform features selection. Our approach involves a dataset of active and non-active molecules collected from ChEMBL database. Our results show the effectiveness of the proposed approach when it comes to predicting accurately active compounds for lung cancer. Furthermore, our comparative analysis reveals important chemical structures that contribute to the effectiveness of the compounds. Thus, the proposed approach can greatly enhance the drug discovery pipeline and may lead to the development of new and effective treatments for lung cancer.
QIVIVE extrapolation requires a precise correlation between exposure and the effective chemical concentration at the site where the MIE occurs.
This work demonstrates that intracellular distribution is not ruled only by physical-chemical parameters, rather it is mainly regulated by specific biological-mediated mechanisms. Substances with
apparent chemical similarity may show different distribution profile, as shown by the intra-nuclear distribution of polyphenols. While our results derive from a limited number of substances applied to
one cell line, it is plausible that using different substances and/or different cell lines would also have shown that intracellular distribution is not directly related to physical-chemical parameters.
Chemical uptake should be specifically measured and simple extrapolations based on physical-chemical properties may provide misleading decision
Pharmacokinetic Properties of Biomass-extracted Substances Isolated by Green ...Michal Jablonsky
According to the literature, approximately 41 nutraceutical compounds have been isolated from different types of biomass using green solvents. It is important to collect information on the pharmacokinetic properties of the nutraceutical substances from biomass isolated according to the published papers. The pharmacokinetic properties of the bioactive substances extracted by green solvents, such as the molecular weight, logP, AlogP, H-bond acceptor, H-bond donor, total polar surface area, atom molar refractivity, number of rotatable bonds, number of atoms, rotatable bond count, number of rigid bonds, number of atom rings, and number of H-bonds, were calculated with a drug-likeness tool. In practical terms, the original and most well-known Lipinski's Rule of Five (Ro5) was applied to 28 substances, namely 3-hydroxytyrosol; apigenin; artemisinin; bergapten; bilobalide; biochanin A; caffeic Acid; caffeoylmalic acid; catechins; cinnamic acid; curcumin; daidzei; daidzin; epicatechin; gallic acid; genistein; ginkgolide A; ginkgolide B; levofloxacin; luteolin; naringenin; p-coumaric acid; protocatechuic acid; psoralen; quercetin; trans-ferulic acid; tyrosol, and vanillin.
Crimson Publishers-Potential Application of Raman Micro-Spectroscopy as an In...CrimsonPublishersMAPP
Potential Application of Raman Micro-Spectroscopy as an In vitro Drug Screening and Companion Diagnostic Tool for Clinical Application: Chemotherapeutic Drug Mechanism of Action, Cellular Effects and Resistance by Z Farhane in Modern Applications in Pharmacy & Pharmacology
WE THE STUDENT OF PHARMACEUTICAL CHEMISTRY FROM GURUNANAK COLLEGE OF PHARMACY HAS PRESENTED QSRR, TO MAKE READERS EASILY AVAILABLE, A COMPLETE TOPIC OF MPHARM 1ST YEAR WHICH WILL MAKE THEIR STUDY AND TO COLLECT DATA MORE EASILY AT A PLACE.
Stable Drug Designing by Minimizing Drug Protein Interaction Energy Using PSO csandit
Each and every biological function in living organism happens as a result of protein-protein interactions. The diseases are no exception to this. Identifying one or more proteins for a
particular disease and then designing a suitable chemical compound (known as drug) to destroy these proteins has been an interesting topic of research in bio-informatics. In previous methods,drugs were designed using only seven chemical components and were represented as a fixedlength
tree. But in reality, a drug contains many chemical groups collectively known as
pharmacophore. Moreover, the chemical length of the drug cannot be determined before
designing the drug.
In the present work, a Particle Swarm Optimization (PSO) based methodology has been
proposed to find out a suitable drug for a particular disease so that the drug-protein interaction
becomes stable. In the proposed algorithm, the drug is represented as a variable length tree and essential functional groups are arranged in different positions of that drug. Finally, the structure of the drug is obtained and its docking energy is minimized simultaneously. Also, the
orientation of chemical groups in the drug is tested so that it can bind to a particular active site of a target protein and the drug fits well inside the active site of target protein. Here, several inter-molecular forces have been considered for accuracy of the docking energy. Results showthat PSO performs better than the earlier methods.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Sagar alone qsar studies of saponin analogues for anticancer activity
1. GUIDED BY- Dr. S. L. DEORE.
Asst. Professor
Govt. College Of Pharmacy,
Amravati.
PRESENTED BY – Mr. SAGAR S. ALONE.
M.Pharm-2nd
(Pharmacognosy & Phytochemistry)
2. Introduction
Review of Literature
Aim & Objective
Need & Scope
Plan of Work
Experimental work
Result & Discussion
Conclusion
Future Scope
References
2Government College Of Pharmacy, Amravati.2August 2013
3. QSAR is the mathematical relationship between the chemical
structure (Describe as Descriptors) and Biological activity.
Physicochemical properties or descriptors are expressed by
numbers.
One can form a mathematical relationship, or quantitative
structure-activity relationship between the two.
The mathematical equation can then be used to predict the
biological response of other chemical structures or analogues.
Biological Activity = ƒ (Physicochemical properties and /or
structural properties)
3Government College Of Pharmacy, Amravati.2August 2013
4. Biological properties
1) Bioconcentration
2) Biodegradation
3) Carcinogenicity
4) Drug metabolism and
clearance
5) Inhibitor constant
6) Mutagenicity
7) Permeability
8) Blood brain barrier
9) Skin
10)Pharmacokinetics
11) Receptor binding
Chemical properties
1) Boiling point
2) Chromatographic
retention time
3) Dielectric constant
4) Diffusion coefficient
5) Dissociation constant
6) Melting point
7) Reactivity
8) Solubility
9) Stability
10) Thermodynamic
properties
11) Viscosity
Government College Of Pharmacy, Amravati. 42August 2013
5. Carcinogens can be present in food ,water, air, in
chemicals and sunlight that people are exposed to.
In 1996 there were 10 million new cancer cases
worldwide and six million deaths attributed to cancer.
In 2020 there are predicted to be 20 million new cases
and 12 million deaths.
A globalization of unhealthy lifestyles, particularly
cigarette smoking and the adoption of many features of
the modern Western diet (high fat, low fibre content)
will increase cancer incidence.
5Government College Of Pharmacy, Amravati.2August 2013
6. Soap-like foaming when shaken in aqueous solutions [4].
Two kinds of saponins are recognized – The steroidal and The pentacyclic
triterpenoid types [5].
More than half of terrestrial plants may contain saponins.
Diversified pharmacological effects (haemolytic, cytotoxic, antitumor, anti-
inflammatory, molluscicidal [9].
Saponins have been shown to induce both cycle arrest and apoptosis within
cancerous cells [10].
Isolation of saponins from plant extracts is often a long and fastidious process
involving many purification steps and usually only small amounts of products
are obtained in a pure and homogeneous form [11].
Therefore, chemical synthesis or semisynthesis of saponin analogue appear to be
a rational way to gain access to adequate amounts of saponins in order to
promote further pharmaceutical studies [12].
6Government College Of Pharmacy, Amravati.2August 2013
7. Quantifying the relationship between structure and
activity.
Biological Activity data provides an understanding of the
effect of structure on activity.
Potential to make predictions leading to the synthesis of
novel analogues.
Help to understand interactions between functional
groups in the molecules of greatest activity, with those of
their target.
7Government College Of Pharmacy, Amravati.2August 2013
8. Modern drug design & drug discovery.
Prediction of biological activity.
Study of different physicochemical properties affecting
biological activity.
Prediction of Chemical toxicity.
To study Mechanism of action.
Prediction of molecular properties.
ADME properties prediction.
8Government College Of Pharmacy, Amravati.2August 2013
9. Siddiqi Mohammad Imran,CDRI Lucknow have been reported which included following
aspects of molecular modeling containing, a technique for the investigation of molecular
structures and Activities/properties using computational chemistry & biology and graphical
visualization techniques in order to provide a plausible 3-D representation [16].
Bang Seong-Cheol, et al, (2005) have been reported antitumor Activity of Pulsatilla koreana
Saponins and Their Structure–Activity Relationship he mentioned Seventeen saponins
isolated from the root of Pulsatilla koreana were examined for their in vitro cytotoxic
activity against the human solid cancer cell lines [17].
Yan L. L et al. (2009) have been reported invitro and in vivo anticancer activity of steroid
saponins of Paris Polyphylla Var. Yunnanensis, to confirm the anticancer activity of steroid
saponins isolated from the rhizome of Paris polyphylla var. yunnanensis and evaluate the
structure-activity relationships of these steroid saponins in vitro and in vivo [18].
Malik Adeel et al. (2006) have been reported Databases and QSAR for Cancer Research in
this review, he take a survey of bioinformatics databases and quantitative structure-activity
relationship studies reported in published literature [19].
9Government College Of Pharmacy, Amravati.2August 2013
10. Gauthier Charles et al. (2009) have been investigated recent Progress in the Synthesis of
Naturally Occurring Triterpenoid Saponins and describe recently reported semi- and total
syntheses of naturally occurring triterpenoid saponins [20].
Matthew J. et al, (2009) have been reported Structural analogues of diosgenyl saponins
synthesis and anticancer activity and he studied Saponins display various biological
activities including anti-tumor activity [21].
Chanin Nantasenamat et al (2009) have been reported a practical overview of quantitative
structure-activity relationship in this review article author describes history and
development of QSAR model and study QSAR modeling pertains to the construction of
predictive models of biological activities as a function of structural and molecular
information of a compound library [1].
Dholwani K. K et al (2008) have been reported on plant derived natural product and their
analogue with antitumor activity” and describes traditional medicine including Chinese
herbal formulation can serve as a potential new drugs and initial research focus on the
isolation of bioactive lead compounds [22].
Tsubuki Masayoshi et al. (2008) has been reported a new synthesis of potent antitumor
saponin OSW-1 Via Witting rearrangement and he work on OSW-1 and its analogues [23].
10Government College Of Pharmacy, Amravati.2August 2013
13. To review saponin analogues having anticancer
activity.
To select training and test set of saponin analogues.
To perform 2D QSAR of selected sets.
To relate different descriptor parameters to saponin
chemical moieties.
To find out specific descriptors affecting anticancer
activity.
To elaborate the role of structural changes in saponin
analogues for Anticancer activity.
Finally to predict the structural changes which tends to
increses anticancer activity.
13Government College Of Pharmacy, Amravati.2August 2013
14. Medical oncology is an important frontier which has gained attention from various research
communities.
The mortality rate of cancer patients is usually high (65%).
Primarily there are three treatment methods for cancer: [24]
Invasive methods - Surgical removal of cancer tissue.
Irradiation methods - Use of high energy radiation.
Chemotherapy - Administration of drugs.
To control cancer from mankind we should discover or make new compound by using QSAR
before going work into actual wet laboratory.
QSAR techniques will continue to make a valuable contribution to the computer-assisted
analysis of structure-bioactivity relationships.
Hence taking into consideration the part of present research which we are performing to do
QSAR study of different saponin analogues having anticancer activity by using Modern
computational technology (QSAR).
14Government College Of Pharmacy, Amravati.2August 2013
15. 1) Literature survey.
2) Selection of saponin analogues for anticancer activity.
3) Study of descriptors.
4) Design and making structure of saponin analogues.
5) QSAR studies.
6) Result and Discussion.
15Government College Of Pharmacy, Amravati.2August 2013
16. Data set-
17 saponins molecules isolated from the Pulsatilla koreana as anticancer agent are
taken from literature for QSAR analysis.[17] Pulsatilla koreana belongs to the family
Ranunculaceae and is an endemic species in Korea containing 17 saponins in which
eight lupane-type (1, 3, 5, 7, 9, 11, 13, 15) and nine oleanane-type (2, 4, 6, 8, 10, 12, 14,
16, 17), isolated from P. koreana roots. Molecule sketching- sketched by using 2D draw
application of VLife MDS (Molecular Design Suite).
2D to 3D- by using VLife MDS (Molecular Design Suite) TM 3.5 software supplied by
VLife Sciences Technologies Pvt. Ltd., Pune, India.
Batch optimization & energy minimization - Batch optimization by taking 100000 cycle
Statistical method- Multiple linear regression (MLR)
QSAR models were generated by a training set of 11 molecules for each model and a
test set of 6 molecules
Training set of molecules (3,4,6,7,11,12,13,14,15,16,17)
Test set of molecules (1,2,5,8,9,10)
GovernmentCollege Of Pharmacy,Amravati. 162August 2013
17. 2D Physicochemical descriptors including Individual, Chi chain, Path count, Chiv,
Element count and Kappa categories and Alignment independent including topological
structure descriptors were calculated for QSAR analysis using Vlife MDS software.
Multiple linear regression method is used to generate QSAR equation.
For validating the quality of the models, Selection of molecules in the training set and
test is a key and important feature of any QSAR model.
Therefore, the care was taken in such a way that biological activities of all compounds
in test lie within the maximum and minimum value range of biological activities of
training set of compounds.
The Uni-Column Statistics of test and training sets further reflected the correct selection
of test and training sets. A Uni-Column statistics for training set and test set were
generated to check correctness of selection criteria for trainings and test set molecules.
MLR is a statistical method for creating linear relationship between a dependent
variable Y (ED50) and independent variable X (2D descriptors).
GovernmentCollege Of Pharmacy,Amravati. 172August 2013
18. Uni-column statistics of the training and test sets for QSAR models
GovernmentCollege Of Pharmacy,Amravati. 18
Cell line Training/Test
set
Average Max Min Std. Dev Sum
A-549 Training set 94.1109 300.000 4.2400 114.9137 1035.2200
Test set 131.5417 300.000 2.5600 138.64.97 789.2500
SK-OV-3 Training set 88.6536 300.0000 3.9500 112.7344 975.1900
Test set 127.3850 300.0000 2.3100 139.3976 764.3100
SK-MEL-2 Training set 94.0000 300.0000 3.0400 116.5289 1034.0000
Test set 136.1183 300.0000 1.5700 139.8473 816.7100
HCT-15 Training set 96.4845 300.0000 5.5000 114.9111 1061.3300
Test set 138.8817 300.0000 8.3600 138.1815 833.2900
Multiple linear Regression equation takes the form
Y = b1 x1 + b2 x2 + b3 x3 + c
Where- Y is dependent variable, ‘b’s are regression coefficients for corresponding ‘x’s
(independent variable), ‘c’ is a regression constant or intercept [6, 7].
2August 2013
19. Statistics of the Models for 4 different cancer cell lines
GovernmentCollege Of Pharmacy,Amravati. 19
Statistics A-549 SK-OV-3 SK-MEL-2 HCT-15
N 11 11 11 11
Degree of freedom 8 8 8 8
r2 0.9281 0.9554 0.9160 0.9203
q2 0.8691 0.9187 0.8285 0.8357
F test 51.6079 85.7357 43.6084 46.1887
r2 se 34.4579 26.6109 37.7639 36.2697
q2 se 46.4909 35.9315 53.9485 52.0702
pred_r2 0.9538 0.9686 0.8950 0.8899
pred_r2se 31.0692 25.8051 47.7110 48.3659
Here:
N - Number of molecules, K - Number of descriptors in a model,
DOF - Degree of freedom (higher is better),
r2 - Coefficient of determination (> 0.7),
q2 - Cross-validated r (>0.5),
pred_r2 - r for external test set (>0.5),
F-test - F-test for statistical significance of the model (higher is better, for same set of descriptors and compounds),
r2_Se, q2_se, pred_r2_se = error for r2, q2, pred_r2 respectively.
2August 2013
20. Here generate four QSAR Equation which is a Mathematical relationship between
Physicochemical properties (Descriptors) & Biological activity
For (A-549):
ED50= + 55.3309( 6.5096) T_2_C_7 + 23.9224( 8.9012) 6ChainCount - 616.7280
For (SK-OV-3):
ED50= + 53.2371( 0.5713) T_2_C_7 + 553.1007( 130.2520) chi6chain -612.2515
For (SK-MEL-2):
ED50 = + 53.9707( 7.2274) T_2_C_7 + 7.3979( 2.5587) T_O_O_5 - 493.8088
For (HCT15):
ED50 = + 53.2728( 6.9414) T_2_C_7 + 7.3583( 2.4574) T_O_O_5 - 484.2732
GovernmentCollege Of Pharmacy,Amravati. 202August 2013
22. 9 PK09 135.28 104.038 114.32 93.2087 165.54 112.479 171.29 114.68
10 PK10 2.56 17.2984 2.31 14.9598 1.57 4.53761 8.36 8.13401
11 PK11 43.64 80.1154 38.90 68.1195 39.67 90.2853 49.04 92.6047
12 PK12 13.49 -6.624 13.71 -10.1294 14.12 -17.6561 14.17 -13.9409
13 PK13 155.32 104.038 124.12 93.2087 145.68 127.275 138.73 129.396
14 PK14 4.24 17.2984 3.95 14.9598 3.47 19.3334 5.50 22.8506
15 PK15 41.35 80.1154 38.91 68.1195 40.02 75.4896 40.86 77.8882
16 PK16 9.58 -6.624 11.39 -10.1294 10.37 -32.4518 12.74 -28.6574
17 PK17 10.73 41.2208 10.66 40.049 9.81 48.925 14.09 52.2837
GovernmentCollege Of Pharmacy,Amravati. 22
From the following data we can conclude that first 4 analogues has no anticancer
activity because all 4 has sugar ester group attached to C-28.
But all analogues from 5 to 17 has free carboxylic acid group at C-28 position and
showing anticancer activity.
2August 2013
23. Graphical representation & comparison of Actual vs. Predicted activity for
training and test set of 4 cancer cell lines
GovernmentCollege Of Pharmacy,Amravati. 23
A-549
SK-OV-3
2August 2013
25. Fitness plot of 4 model for 4 different cancer cell lines
Government College Of Pharmacy, Amravati. 25
A-549 SK-OV-3
SK-MEL-2
HCT-15
2August 2013
26. Contribution plot of 4 model for 4 different cancer cell lines showing
which descriptors are responsible for anticancer activity
Government College Of Pharmacy, Amravati.
26
A-549 SK-OV-3
SK-MEL-2 HCT 15
2August 2013
27. I have evaluated a series of Pulsatilla koreana saponin analogues by doing 2D QSAR with the help of
different descriptors in order to determine the better structural characteristics and to study different
descriptors responsible for anticancer activity.
From the QSAR studies it was found that the Alignment Independent category is most responsible for all 4
types of cancer cell lines which includes
T_2_C_7: This is the count of No. of double bounded atoms (i.e. - Any double bonded atoms, T-2)
separated from carbon atom by 7 bonds in a molecule.
T_O_O_5: This is the count of No. of oxygen atoms (Single double or triple bounded) separated from
other other oxygen by 5 bond distance in a molecule.
6chain count: These descriptors signify total numbers of six membered rings in a compound.
Chi6chain: These descriptors signify a retention index for six membered rings.
It was found that all descriptors have positive correlation with the anticancer activity.
Hence increase in all descriptor values will help to increase the anticancer activity of Pulsatilla koreana
saponins analogues for anticancer activity.
Hence, the model proposed in this work is useful and can be employed to design new saponin derivative of
Pulsatilla koreana as most active anticancer agent.
GovernmentCollege Of Pharmacy,Amravati. 272August 2013
28. To determine the better structural characteristics
and to study different descriptors (3D
Descriptors) responsible for anticancer activity
(3D QSAR Study).
To identify all other cancer cell lines to which
Pulsatilla koreana saponin analogues exhibits its
affinity/Inhibition potential.
To design new saponin derivative of Pulsatilla
koreana as most active anticancer agent.
GovernmentCollege Of Pharmacy,Amravati. 282August 2013
29. [1] Chanin Nantasenamat et.al. (2009) A practical overview of quantitative structure-activity relationship, excli Journal, pp.74-88.
[2] Tatsuhiko Yoshino, (2010) QSAR in Catalysis in Silico Catalyst Design, pp.1-15.
[3] Alison Malcolm R, (2001) Cancer. Encyclopedia of life sciences, Nature Publishing Group, pp.1-8.
[4] Hostettmann, K et.al. (1995). Saponins. Cambridge: Cambridge University Press. Pp.32970-71.
[5] Osbourn, A. (1996) Saponins and plant defence – a soap story. Trends Plant Sci. vol 1, pp 4-9.
[6] Vincken, J. P.et.al. (2007) Saponins, classification. And occurrence in the plant kingdom. Phytochemistry, 68, pp.275 297.
[7] Agrawal, P. K et.al. (1985) Carbon-13 NMR spectroscopy of steroidal sapogenins and steroidal saponins. Phytochemistry,
pp.2479-2496.
[8] Agrawal, P. K. et.al. (1992) NMR spectroscopy of oleanane triterpenoids. Prog. Nucl. Mag, pp.1-90.
[9] Agrawal, P. K et.al. (1996) Nuclear magnetic resonance spectroscopic approaches for the determination of interglycosidic
linkage and sequence in oligosaccharides. Phytochem. Anal.7, pp.113-130.
[10] Sahu N. P et.al. (2001) Advances in structural determination of saponins and terpenoid glycosides. Curr. Org. Chem 5, pp.315-
334.
[11] Qin, G. W et.al. (1998) Some progress on chemical studies of triterpenoid saponins from Chinese medicinal plants. Curr. Org.
Chem 2, pp.613-625.
[12] Liu, J.et.al. (2002) Traditional Chinese medicine (TCM): Are polyphenols and saponins the key ingredients triggering biological activities? Curr
Med. Chem 9, pp.1483-1485.
29Government College Of Pharmacy, Amravati.2August 2013
30. [13] Riguera, Ricardo, (1997). Isolating bioactive compounds from marine organisms Journal of Marine Biotechnology 5 (4) pp.187–193.
[14] Liener, Irvin E (1980). Toxic constituents from plant foodstuffs. New York City: Academic Press. p.161.
[15] Francis, George et.al. (2002). The biological action of saponins in animal Systems: a review. British Journal of Nutrition 88 (6): pp.587–605.
[16] Mohammad Imran Siddiqi, (2007) QSAR: Principles and Selected Case Studies, CDRI, Lucknow.
[17] Seong-Cheol Bang, et al (2005) Antitumor Activity of Pulsatilla koreana Saponins and Their Structure–Activity Relationship Chem. Pharm.
Bull, pp.1451—1454.
[18] L.L. Yan, et al (2009) In vitro and in vivo anticancer activity of steroid saponins of Paris Polyphylla var. Yunnanensis Exp Oncol pp.27–32.
[19] Malik Adeel, Singh Hemajit, et al. (2006) Databases and QSAR for cancer research cancer informatics, Cancer Inform 2: pp.99–111.
[20] Charles Gauthier et.al. (2009) Recent Progress in the Synthesis of Naturally Occurring Triterpenoid Saponins, Mini-Reviews in Organic
Chemistry vol-6, pp.321-344.
[21] Kaskiw M. J et al, (2009) Structural analogues of diosgenyl saponins: Synthesis and anticancer activity, Bioorg. Med. Chem pp.7670–7679.
[22] Dholwani K.K., et al, (2008) A review on plant derived natural product and their analogue with antitumor activity, Indian J pharmacol Apr, issue
2, pp.49-58.
[23] Masayoshi Tsubuki et. al. (2008) A new synthesis of potent antitumor saponin OSW-1Via Wittig rearrangement Tetrahedron, pp.229–232.
[24] Paila, Hari Srinivas Kalyan, (2008) M.S. Molecular Modeling Studies of Curcumin Analogs as Anti-Angiogenic Agents pp.97.
30Government College Of Pharmacy, Amravati.2August 2013