THREE-DIMENSIONAL QSAR MODELING BENZIMIDAZOLE ANALOGUES USING THE K-NEAREST NEIGHBOR METHOD

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (12) ◽  
pp. 62-67
Author(s):  
M. C Sharma ◽  
◽  
D. V. Kohli
Keyword(s):  
Nearest Neighbor ◽  
Three Dimensional ◽  
Antihypertensive Agents ◽  
3D Qsar ◽  
Good Alternative ◽  
Qsar Model ◽  
Field Analysis ◽  
K Nearest Neighbor ◽  
Qsar Modeling ◽  
Qsar Studies

We undertook the three-dimensional (3D) QSAR studies of a series of benzimidazole analogues to elucidate the structural properties required for angiotensin II. The 3D-QSAR studies were performed using the stepwise, simulated annealing (SA) and genetic algorithm (GA) selection k-nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient q2 = 0.8216 and a pred_r2 = 0.7852 were obtained. The 3D QSAR model is expected to provide a good alternative to predict the biological activity prior to synthesis as antihypertensive agents.

PREDICTIVE QSAR MODELING OF PYRIDAZINYL DERIVATIVES USING K-NEAREST NEIGHBOR AND PHARMACOPHORE APPROACH

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (07) ◽  
pp. 10-17
Author(s):  
M.C. Sharma ◽  
◽  
D.V. Kohli
Keyword(s):  
Correlation Coefficient ◽  
Nearest Neighbor ◽  
Predictive Ability ◽  
3D Qsar ◽  
Qsar Model ◽  
Field Analysis ◽  
Angiotensin Ii Receptor ◽  
K Nearest Neighbor ◽  
Qsar Modeling ◽  
Leave One Out

This study was carried out elucidate the structural properties required for pyridazinyl derivatives to exhibit angiotensin II receptor activity. The best 2D-QSAR model was selected, having correlation coefficient r2 = 0.8156, cross validated squared correlation coefficient q2 = 0.7348 and predictive ability of the selected model was also confirmed by leave one out cross validation method. Further analysis was carried out using 3D-QSAR method k-nearest neighbor molecular field analysis approach; a leave-one-out crossvalidated correlation coefficient of 0.7188 and a predictivity for the external test set (0.7613) were obtained. By studying the QSAR models, one can select the suitable substituent for active compound with maximum potency.

DEVELOPMENT OF A CREDIBLE QSAR AND K NEAREST NEIGHBOR MODELS FOR IMIDAZOLYL DERIVATIVES

INDIAN DRUGS ◽  
2018 ◽  
Vol 55 (05) ◽  
pp. 7-13
Author(s):  
M. C Sharma ◽  
Keyword(s):  
Correlation Coefficient ◽  
Nearest Neighbor ◽  
Antihypertensive Agents ◽  
3D Qsar ◽  
Qsar Model ◽  
Structural Features ◽  
Field Analysis ◽  
Molecular Field ◽  
K Nearest Neighbor ◽  
Molecular Field Analysis

Quantitative Structure-Activity Relationship studies were performed for correlating the imidazolyl derivatives and their activity using molecular modeling studies. The statistically significant best 2D model was having correlation coefficient = 0.8221 and cross-validated squared correlation coefficient = 0.7534 with external predictive ability of pred_r2 = 0.7716. Molecular field analysis was used to construct the best 3D-QSAR model showing good correlative and predictive capabilities in terms of q2 =0.6781 and pred_r2 =0.7299. The molecular field analysis (MFA) contour plots provided further understanding of the relationship between structural features of Imidazolyl derivatives and their activities which should be applicable to design newer potential antihypertensive agents.

scholarly journals Structural investigations of CXCR2 receptor antagonists by CoMFA, CoMSIA and flexible docking studies

2012 ◽  
Vol 62 (3) ◽  
pp. 287-304 ◽  
Author(s):  
Shravan Kumar Gunda ◽  
Rohith Kumar Anugolu ◽  
Sri Ramya Tata ◽  
Saikh Mahmood
Keyword(s):  
Standard Error ◽  
Three Dimensional ◽  
3D Qsar ◽  
Homology Model ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Structural Investigations ◽  
Qsar Analysis ◽  
Qsar Studies

= Three-dimensional quantitative structure activity relationship (3D QSAR) analysis was carried out on a et of 56 N,N’-diarylsquaramides, N,N’-diarylureas and diaminocyclobutenediones in order to understand their antagonistic activities against CXCR2. The studies included comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Models with good predictive abilities were generated with CoMFA q2 0.709, r2 (non-cross-validated square of correlation coefficient) = 0.951, F value = 139.903, r2 bs = 0.978 with five components, standard error of estimate = 0.144 and the CoMSIA q2 = 0.592, r2 = 0.955, F value = 122.399, r2 bs = 0.973 with six components, standard error of estimate = 0.141. In addition, a homology model of CXCR2 was used for docking based alignment of the compounds. The most active compound then served as a template for alignment of the remaining structures. Further, mapping of contours onto the active site validated each other in terms of residues involved with reference to the respective contours. This integrated molecular docking based alignment followed by 3D QSAR studies provided a further insight to support the structure-based design of CXCR2 antagonistic agents with improved activity profiles. Furthermore, in silico screening was adapted to the QSAR model in order to predict the structures of new, potentially active compounds.

scholarly journals Docking and 3D QSAR Studies on p38α MAP Kinase Inhibitors

2011 ◽  
Vol 8 (4) ◽  
pp. 1596-1605
Author(s):  
Mohan Babu Jatavath ◽  
Sree Kanth Sivan ◽  
Yamini Lingala ◽  
Vijjulatha Manga
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Model ◽  
Chemotherapeutic Agents ◽  
Field Analysis ◽  
Qsar Studies

The p38 signaling cascade has emerged as an attractive target for the design of novel chemotherapeutic agents for the treatment of inflammatory diseases. Three dimensional quantitative structure- activity relationship (3D- QSAR) studies were performed on a series of 25, 2-aminothiazole analogs as inhibitors of p38α mitogen activated protein (MAP) kinase. The docking results provided a reliable conformational alignment scheme for the 3D-QSAR model. The 3D-QSAR model showed very good statistical results namely q2, r2and r2predvalues for both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models & docking results provided the most significant correlation of steric, electrostatic, hydrophobic,H-bond donor,H-bond acceptor fields with biological activities and the provided values were in good agreement with the experimental results. The information rendered from molecular modeling studies gave valuable clues to optimize the lead and design new potential inhibitors.

QSAR STUDIES ON HUMAN CARBONIC ANHYDRASE II INHIBITORS

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (11) ◽  
pp. 18-28
Author(s):  
Tanvi V. Wani ◽  
◽  
Mrunmayee P. Toraskar
Keyword(s):  
Carbonic Anhydrase ◽  
Nearest Neighbor ◽  
3D Qsar ◽  
Field Analysis ◽  
Molecular Field ◽  
Carbonic Anhydrase Ii ◽  
Carbonic Anhydrases ◽  
K Nearest Neighbor ◽  
Qsar Studies ◽  
Molecular Field Analysis

Carbonic anhydrase II is one of the forms of human α carbonic anhydrases which are ubiquitous metalloenzymes that catalyze inter-conversion of carbon dioxide and water to bicarbonate and proton, overexpression of which leads to disorders such as glaucoma. 2D and 3D Quantitative Structure Activity Relationship studies were carried out on previously synthesized series of sulfanilamide derivatives by VLife MDS software using stepwise variable, multi-linear regression and k-nearest neighbor molecular field analysis methods. 2D-QSAR model depicts contribution of halogens (such as chlorine and fluorine), methylene and oxygen atoms to inhibition of human carbonic anhydrases II activity. Using k-nearest neighbor molecular field analysis method two 3D-QSAR models (model A and B) were generated from which model A was found to be the best validated model with q2 (0.9494), pred_r2 (0.7367) and q2 _ se (0.2037). It displayed the fact that the inhibitory action of sulfanilamide derivatives against human carbonic anhydrases II is influenced by hydrophobicity and electro positivity.

INSIGHT INTO THE STRUCTURAL REQUIREMENTS OF SULFONYL DERIVATIVES BASED ON TWO AND THREE-DIMENSIONAL DESCRIPTORS: QSAR STUDIES

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (01) ◽  
pp. 81-86
Author(s):  
M. C Sharma ◽  
Keyword(s):  
Nearest Neighbor ◽  
Three Dimensional ◽  
Structural Features ◽  
At1 Receptor ◽  
Field Analysis ◽  
K Nearest Neighbor ◽  
Qsar Studies ◽  
Contour Plots ◽  
The Relationship ◽  
Insight Into

The present work provides the rationale to the changes in the structure to have more potent analogs sulfonyl derivatives were reported to possess potent activity for the angiotensin AT1 receptor. We report here 2D QSAR and k-nearest neighbor molecular field analysis based model for sulfonylureas compounds as AT1 receptor. The here k-nearest neighbor contour plots provided further understanding of the relationship between structural features of substituted sulfonyl derivatives and their activities which should be applicable to design newer potential AT1 receptor.

DEVELOPMENT OF A ROBUST QSAR MODEL OF ANGIOTENSIN RECEPTOR REVEALS A K NEAREST NEIGHBOR APPLICABLE TO DIVERSE SCAFFOLDS

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (06) ◽  
pp. 30-36
Author(s):  
M. C Sharma ◽  
◽  
D. V. Kohli
Keyword(s):  
Biological Activity ◽  
Nearest Neighbor ◽  
3D Qsar ◽  
Qsar Model ◽  
Partial Least Square ◽  
Least Square ◽  
Positive Contribution ◽  
K Nearest Neighbor ◽  
Qsar Studies ◽  
2D Qsar

Quantitative structure–activity relationship (QSAR) studies were performed on quinazolinone analogues for prediction of antihypertensive activity. The best significant 2D-QSAR model having r2 = 0.8118 and pred_r2 = 0.7428 was developed by stepwise-partial least square method. k-nearest neighbor molecular field analysis was used to construct the best 3D-QSAR model, showing good correlative and predictive capabilities in terms of q2 = 0.7388 and pred_r2 = 0.6983. Results reveal that the 2D-QSAR studies signify positive contribution of SssOE index and SsCH3 count towards the biological activity. The results have showed that electronegative groups are necessary for activity and halogen, bulky, less bulky groups in quinazolinones nucleus enhanced the biological activity. The information rendered by 2D- and 3D-QSAR models may lead to a better understanding of structural requirements of substituted quinazolinones derivatives and also aid in designing novel potent antihypertensive molecules.

DESIGN OF POTENTIAL CYCLOOXYGENASE INHIBITORS USING PHARMACOPHORE OPTIMIZATION BY MOLECULAR MODELING STUDIES

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (12) ◽  
pp. 16-22
Author(s):  
S. S Todkar ◽  
◽  
A. H. Hoshmani
Keyword(s):  
Molecular Modeling ◽  
Nearest Neighbor ◽  
3D Qsar ◽  
Field Analysis ◽  
K Nearest Neighbor ◽  
Qsar Studies ◽  
2D Qsar ◽  
Molecular Modeling Studies ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Recently discovery of relation between cyclooxygenase–2 (COX–2) inhibition and prevention of growth of cansar cells is a major area for research in medicinal chemistry, as it is free from side effects which are genetically shown by developed anticancer agents. In an attempt to develop potent and nontoxic COX–2 inhibitors, we have optimized the 1,5- diaryl pyrazole pharmacophore by using molecular modeling studies. In this paper we present results of 2D and 3D QSAR studies of a series of 22 molecules containing 1,5- diaryl pyrazole pharmacophore as selective COX–2 inhibitors. The 3D QSAR studies were performed using two different methods, stepwise variable selection k–nearest neighbor molecular field analysis (SW kNN–MFA) and simulated annealing k–nearest neighbor molecular field analysis (SA kNN–MFA) methods. The 2D QSAR studies were performed using multiple regressions. 3D QSAR studies produced reasonably good predictive models with high cross–validated r2cv value of 0.732 and 0.783 and predicted r2 value of 0.882 and 0.794 values using the models SW kNN–MFA and SA kNN–MFA method, respectively, whereas the r2 & predicted r2 value in 2D QSAR studies was found to be 0.84914 & 0.9157, respectively. the 2D QSAR studies indicated contribution of different physicochemical descriptors and the result of 3D QSAR studies indicated the exact steric and electronic requirement in the ranges at various positions in the 1,5- diaryl pyrazole pharmacophore. The pharmacophore requirement for selective COX–2 inhibition was optimized and requirement at various positions around 1, 5- diaryl pyrazole pharmacophore were defined.

3D-QSAR Studies of S-DABO Derivatives as Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

2019 ◽  
Vol 16 (8) ◽  
pp. 868-881
Author(s):  
Yueping Wang ◽  
Jie Chang ◽  
Jiangyuan Wang ◽  
Peng Zhong ◽  
Yufang Zhang ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Three Dimensional ◽  
Predictive Ability ◽  
3D Qsar ◽  
Binding Mode ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Reverse Transcriptase Inhibitors ◽  
Qsar Studies ◽  
Hiv 1

Background: S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. Methods: In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of 38 S-DABO analogues developed in our lab was studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). The Docking/MMFF94s computational protocol based on the co-crystallized complex (PDB ID: 1RT2) was used to determine the most probable binding mode and to obtain reliable conformations for molecular alignment. Statistically significant CoMFA (q2=0.766 and r2=0.949) and CoMSIA (q2=0.827 and r2=0.974) models were generated using the training set of 30 compounds on the basis of hybrid docking-based and ligand-based alignment. Results: The predictive ability of CoMFA and CoMSIA models was further validated using a test set of eight compounds with predictive r2 pred values of 0.843 and 0.723, respectively. Conclusion: The information obtained from the 3D contour maps can be used in designing new SDABO derivatives with improved HIV-1 inhibitory activity.

Computational Studies of 3D-QSAR on a Highly Active Series of Naturally Occurring Nonnucleoside Inhibitors of HIV-1 RT (NNRTI)

2020 ◽  
pp. 2050036
Author(s):  
Waqar Hussain ◽  
Arshia Majeed ◽  
Ammara Akhtar ◽  
Nouman Rasool
Keyword(s):  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Modeling ◽  
Qsar Analysis ◽  
Qsar Studies ◽  
Highly Active ◽  
Naturally Occurring ◽  
Zinc Database ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

HIV is one of the deadliest viruses in the history of mankind, it is the root cause of Acquired Immunodeficiency Syndrome (AIDS) around the world. Despite the fact that the antiviral therapy used against HIV-1 infection is effective, there is also rapidly growing cases of drug resistance in the infected patient along with different severe side effects. Therefore, it is of dire and immediate need to find novel inhibitors against HIV-1 Reverse Transcriptase (RT). In this study, the potential of naturally occurring compounds extracted from plants has been studied with the help of Three-Dimensional-Quantitative Structure–Activity Relationships (3D-QSAR) analysis. A total of 20 compounds, retrieved from a ZINC database, were analyzed with the help of 3D-QSAR to identify a potential inhibitor of HIV-1 RT. By evaluation of seven models generated with the help of MIF analysis and 3D-QSAR modeling, compound 3 (ZINC ID: ZINC20759448) was observed to outperform others by showing optimal results in QSAR studies. This compound has also been biologically validated by a recently reported previous study. Thus, this compound can be used as a potential drug against infection caused by HIV-1, specifically AIDS.

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