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.

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.

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.

scholarly journals 3D-QSAR and Docking Studies of a Series ofβ-Carboline Derivatives as Antitumor Agents of PLK1

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jahan B. Ghasemi ◽  
Valentin Davoudian
Keyword(s):  
Antitumor Agents ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Docking Studies ◽  
Human Tumor Cell Lines ◽  
Qsar Analysis ◽  
Leave One Out

An alignment-free, three dimensional quantitative structure-activity relationship (3D-QSAR) analysis has been performed on a series ofβ-carboline derivatives as potent antitumor agents toward HepG2 human tumor cell lines. A highly descriptive and predictive 3D-QSAR model was obtained through the calculation of alignment-independent descriptors (GRIND descriptors) using ALMOND software. For a training set of 30 compounds, PLS analyses result in a three-component model which displays a squared correlation coefficient (r2) of 0.957 and a standard deviation of the error of calculation (SDEC) of 0.116. Validation of this model was performed using leave-one-out,q2looof 0.85, and leave-multiple-out. This model gives a remarkably highr2pred(0.66) for a test set of 10 compounds. Docking studies were performed to investigate the mode of interaction betweenβ-carboline derivatives and the active site of the most probable anticancer receptor, polo-like kinase protein.

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 Thiazole Derivatives as HCV NS5A Inhibitors via CoMFA and CoMSIA Methods

2019 ◽  
Vol 16 (4) ◽  
pp. 453-460 ◽  
Author(s):  
Jiayu Li ◽  
Wenyue Tian ◽  
Diaohui Gao ◽  
Yuying Li ◽  
Yiqun Chang ◽  
...  
Keyword(s):  
Nonstructural Protein ◽  
External Validation ◽  
Three Dimensional ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Thiazole Derivatives ◽  
Hydrogen Bond Acceptor ◽  
Qsar Studies ◽  
Comfa Model

Background: Hepatitis C Virus (HCV) infection is the major cause of hepatitis after transfusion. And HCV Nonstructural Protein 5A (NS5A) inhibitors have become a new hotspot in the study of HCV inhibitors due to their strong antiviral activity, rapid speed of viral removing and broad antiviral spectrum. Methods: Forty-five NS5A inhibitors were chosen to process three-dimensional quantitative structure- activity relationship (3D-QSAR) by using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. A training set consisting of 30 compounds was applied to establish the models and a test set consisting of 15 compounds was applied to do the external validation. Results: The CoMFA model predicted a q2 value of 0.607 and an r2 value of 0.934. And the CoMSIA model predicted a q2 value of 0.516 and an r2 value of 0.960 established on the effects of steric, electrostatic, hydrophobic and hydrogen-bond acceptor. 0.713 and 0.939 were the predictive correlation co-efficients (r2pred) of CoMFA and CoMSIA models, respectively. Conclusion: These conclusions provide a theoretical basis for drug design and screening of HCV NS5A complex inhibitors.

scholarly journals QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS OF NOVEL PYRAZOLINE DERIVATIVES USING K NEAREST NEIGHBOUR MOLECULAR FIELD ANALYSIS METHOD

2017 ◽  
Vol 9 (12) ◽  
pp. 87
Author(s):  
Deepali M. Jagdale ◽  
Ramaa C. S.
Keyword(s):  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Quantitative Structure ◽  
Relationship Analysis ◽  
Structure Activity ◽  
Novel Approach ◽  
Vlife Mds

Objective: Malonyl CoA decarboxylase (MCD) enzyme plays important role in fatty acid and glucose oxidation. Inhibition of MCD might turn to a novel approach to treat ischemia. The main objective of this research article was to develop a novel pharmacophore for enhanced activity.Methods: Three-dimensional quantitative structure-activity relationships (3D-QSAR) was performed for pyrazoline derivatives as MCD inhibitors using VLife MDS 4.6 software. The QSAR model was developed using the stepwise 3D-QSAR kNN-MFA method.Results: The statistical results generated from kNN-MFA method indicated the significance and requirements for better MCD inhibitory activity. The information rendered by 3D-QSAR model may render to better understanding and designing of novel MCD inhibitors.Conclusion: 3D-QSAR is an important tool in understanding the structural requirements for the design of novel and potent MCD inhibitors. It can be employed to design new drug discovery.

Receptor-Based 3D QSAR Analysis of Serotonin 5-HT1D Receptor Agonists

2005 ◽  
Vol 70 (9) ◽  
pp. 1482-1492 ◽  
Author(s):  
Nalan Terzioglu ◽  
Hans-Dieter Höltje
Keyword(s):  
Excellent Result ◽  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Dynamic Simulations ◽  
Qsar Analysis ◽  
Receptor Agonists ◽  
Predictive Quality ◽  
Serotonergic Receptor

A three-dimensional quantitative structure-activity relationship study (3D QSAR) has been successfully applied to explain the binding affinities for the serotonin 5-HT1D receptor of a triptan series. The paper describes the development of a receptor-based 3D QSAR model of some known agonists and recently developed triptans on the 5-HT1D serotonergic receptor, showing a significant correlation between predicted and experimentally measured binding affinity (pIC50). The pIC50 values of these agonists are in the range from 5.40 to 9.50. The ligand alignment obtained from dynamic simulations was taken as basis for a 3D QSAR analysis applying the GRID/GOLPE program. 3D QSAR analysis of the ligands resulted in a model of high quality (r2 = 0.9895, q2LOO = 0.7854). This is an excellent result and proves both the validity of the proposed pharmacophore and the predictive quality of the 3D QSAR model for the triptan series of serotonin 5-HT1D receptor agonists.

scholarly journals Receptor Guided 3D-QSAR: A Useful Approach for Designing of IGF-1R Inhibitors

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
M. Muddassar ◽  
F. A. Pasha ◽  
H. W. Chung ◽  
K. H. Yoo ◽  
C. H. Oh ◽  
...  
Keyword(s):  
Structural Information ◽  
Three Dimensional ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Comparative Molecular Field Analysis ◽  
Qsar Studies ◽  
Similarity Indices ◽  
Qsar Models ◽  
Derivatives Of

Research by other investigators has established that insulin-like growth factor‐1 receptor (IGF-1R) is a key oncological target, and that derivatives of 1, 3-disubstituted-imidazo[1,5-] pyrazine are potent IGF-1R inhibitors. In this paper, we report on our three-dimensional quantitative structure activity relationship (3D-QSAR) studies for this series of compounds. We validated the 3D-QSAR models by the comparison of two major alignment schemes, namely, ligand-based (LB) and receptor-guided (RG) alignment schemes. The latter scheme yielded better 3D-QSAR models for both comparative molecular field analysis (CoMFA) (, ) and comparative molecular similarity indices analysis (CoMSIA) (, ). We submit that this might arise from the more accurate inhibitor alignment that results from using the structural information of the active site. We conclude that the receptor-guided 3D-QSAR may be helpful to design more potent IGF-1R inhibitors, as well as to understand their binding affinity with the receptor.

scholarly journals Docking-Guided 3D-QSAR Studies of 4-Aminoquinoline-1,3,5-triazines as Inhibitors for Plasmodium falciparum Dihydrofolate Reductase

2020 ◽  
Vol 20 (6) ◽  
pp. 1455
Author(s):  
Radite Yogaswara ◽  
Maria Ludya Pulung ◽  
Sri Hartati Yuliani ◽  
Enade Perdana Istyastono
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Multiple Drug Resistance ◽  
Three Dimensional ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Multiple Drug ◽  
Qsar Analysis ◽  
Qsar Studies ◽  
Molecular Determinants

Mutations in Plasmodium falciparum dihydrofolate reductase (PfDHFR), together with other mutations, hinder malaria elimination in Southeast Asia due to multiple drug resistance. In this article, molecular docking-guided three-dimensional (3D) quantitative structure-activity relationship (QSAR) analysis of 4-aminoquinoline-1,3,5-triazines as inhibitors for the wild-type (WT) PfDHFR to identify the molecular determinants of the inhibitors binding are presented. Compounds 4-aminoquinoline-1,3,5-triazines were reported promising to be developed as the non-resistant drugs. The 3D-QSAR analysis resulted in the best model with the R2 and Q2 values of 0.881 and 0.773, respectively. By correlating the molecular interaction fields (MIFs) of the best model to the docking pose employed to guide the 3D-QSAR analysis, S108 residue of the WT-PfDHFR was unfortunately recognized as one of the molecular determinants. Since the S108 residue is one of the mutation points of the PfDHFR mutants, the subsequent design strategy should modify the morpholine moiety to avoid the interaction with the S108 residue of the WT-PfDHFR.

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