Application of CoMFA and CoMSIA 3D-QSAR and Docking Studies in Optimization of Mercaptobenzenesulfonamides as HIV-1 Integrase Inhibitors

2004 ◽  
Vol 47 (2) ◽  
pp. 385-399 ◽  
Author(s):  
Chih-Ling Kuo ◽  
Haregewein Assefa ◽  
Shantaram Kamath ◽  
Zdzialaw Brzozowski ◽  
Jaroslaw Slawinski ◽  
...  
Keyword(s):  
3D Qsar ◽  
Docking Studies ◽  
Integrase Inhibitors ◽  
Hiv 1

Design, Synthesis and Docking Studies of Thioimidazolyl Diketoacid Derivatives Targeting HIV-1 Integrase

2021 ◽  
Vol 17 ◽  
Author(s):  
Nafiseh Karimi ◽  
Rouhollah Vahabpour Roudsari ◽  
Zahra Hajimahdi ◽  
Afshin Zarghi
Keyword(s):  
Drug Target ◽  
Enzyme Assay ◽  
Binding Mode ◽  
Docking Studies ◽  
Integrase Inhibitors ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Novel Structures ◽  
Anti Hiv ◽  
Hiv 1

Background: Integrase enzyme is a validated drug target to discover novel structures as anti-HIV-1 agents. Objective: Novel series of thioimidazolyl diketo acid derivatives characterizing various substituents at N-1 and 2-thio positions of central ring were developed as HIV-1 integrase inhibitors. Results: The obtained molecules were evaluated in the enzyme assay, displaying promising integrase inhibitory activity with IC50 values ranging from 0.9 to 7.7 M. The synthesized compounds were also tested for antiviral activity and cytotoxicity using HeLa cells infected by the single-cycle replicable HIV-1 NL4-3. Conclusion: The most potent compound was 18i with EC50=19 µM, IC50 0.9 µM and SI= 10.5. Docking studies indicated that the binding mode of the active molecule is well aligned with the known HIV-1 integrase inhibitors.

3D-QSAR and Docking Studies on the HEPT Derivatives of HIV-1 Reverse Transcriptase

2011 ◽  
Vol 78 (3) ◽  
pp. 418-426 ◽  
Author(s):  
Ramaswamy Sree Latha ◽  
Ramadoss Vijayaraj ◽  
Ettayapuram Ramaprasad Azhagiya Singam ◽  
Krishnaswamy Chitra ◽  
Venkatesan Subramanian
Keyword(s):  
Reverse Transcriptase ◽  
3D Qsar ◽  
Docking Studies ◽  
Derivatives Of ◽  
Hept Derivatives ◽  
Hiv 1

scholarly journals Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors

2011 ◽  
Vol 19 (6) ◽  
pp. 2030-2045 ◽  
Author(s):  
Horrick Sharma ◽  
Shivaputra Patil ◽  
Tino W. Sanchez ◽  
Nouri Neamati ◽  
Raymond F. Schinazi ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
3D Qsar ◽  
Biological Evaluation ◽  
Integrase Inhibitors ◽  
Qsar Studies ◽  
Hiv 1

QSAR and Docking Studies of DATA Analogues as HIV-1 Reverse Transcriptase Inhibitors

2018 ◽  
Vol 16 (2) ◽  
pp. 153-159 ◽  
Author(s):  
Jianbo Tong ◽  
Shan Lei ◽  
Pei Zhan ◽  
Shangshang Qin ◽  
Yang Wang
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Reverse Transcriptase ◽  
3D Qsar ◽  
Docking Studies ◽  
Reverse Transcriptase Inhibitors ◽  
Electronic Density ◽  
Topomer Comfa ◽  
Rt Inhibitors ◽  
Hiv 1

Background: Acquired Immunodeficiency Syndrome (AIDS) caused by Human Immunodeficiency Virus (HIV) has seriously threatened human health, so development of new, selective and safe non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) remains a high priority for medical research. Diaryltriazine (DATA) have been identified as a new class of potent nonnucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. The study deals with Topomer CoMFA (Comparative Molecular Field Analysis) and molecular docking to explore the important features of DATA analogues for exerting potent HIV-1 RT inhibitors activity. Methods: In this work, 40 DATA analogues were studied using a combination of molecular modeling techniques including Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR), molecular docking, and Topomer CoMFA were used to build 3D-QSAR models. Results: The results show that the Topomer CoMFA analysis has the cross-validation q2 = 0.800, SDCV = 0.45, the non-cross-validated r2 = 0.958, SD = 0.21, and the correlation coefficient of external validation Q2 ext = 0.965 showed that the model is reasonable and credible, and has a good predictive ability. Then binding mode pattern of the compounds to the binding site of enzyme was confirmed and the mechanism of drug and acceptor was studied by docking studies, the results showed that the drug and GLU138, LYS101, THR139 sites have an obvious function, these researches have provided an useful information for designing more effective HIV-1IN inhibitors. Conclusion: A series of 40 DATAs analogues was subjected to a 3D-QSAR study. Using Topomer CoMFA 3D-QSAR method built model, and the model has shown a good predictive and statistical validation. Substituent with low electronic density in the R5 and R3 positions and substituent with high electronic density in the R2 and C2 positions will increase the biological activity, small substituent on R4 positions and naphthyloxy as the spacer group C6 substituent hydrophobic will increase biological activity. This effect is supported by Topomer CoMFA contour map and docking results of HIV-1RT inhibition active site, the results of the 3D-QSAR and docking analyses have provided a guide for the synthesis of new putative inhibitors for HIV-1RT to improved inhibitory activity.

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