CoMFA and CoMSIA 3D QSAR and Docking Studies on Conformationally-Restrained Cinnamoyl HIV-1 Integrase Inhibitors:  Exploration of a Binding Mode at the Active Site

2002 ◽  
Vol 45 (4) ◽  
pp. 841-852 ◽  
Author(s):  
John K. Buolamwini ◽  
Haregewein Assefa
Keyword(s):  
Active Site ◽  
3D Qsar ◽  
Binding Mode ◽  
Docking Studies ◽  
Integrase Inhibitors ◽  
Conformationally Restrained ◽  
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.

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

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.

scholarly journals Structural Basis for the Inhibition of RNase H Activity of HIV-1 Reverse Transcriptase by RNase H Active Site-Directed Inhibitors

2010 ◽  
Vol 84 (15) ◽  
pp. 7625-7633 ◽  
Author(s):  
Hua-Poo Su ◽  
Youwei Yan ◽  
G. Sridhar Prasad ◽  
Robert F. Smith ◽  
Christopher L. Daniels ◽  
...  
Keyword(s):  
Active Site ◽  
Thermal Denaturation ◽  
Binding Mode ◽  
Rnase H ◽  
New Drugs ◽  
Structural Basis ◽  
Independent Manner ◽  
Approved Drugs ◽  
Hiv 1 ◽  
Rapid Emergence

ABSTRACT HIV/AIDS continues to be a menace to public health. Several drugs currently on the market have successfully improved the ability to manage the viral burden in infected patients. However, new drugs are needed to combat the rapid emergence of mutated forms of the virus that are resistant to existing therapies. Currently, approved drugs target three of the four major enzyme activities encoded by the virus that are critical to the HIV life cycle. Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by directly engaging the RNase H active site. Here, we describe structures of naphthyridinone-containing inhibitors bound to the RNase H active site. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain. In addition, one of the naphthyridinone-based compounds was found to bind at a second site close to the polymerase active site and non-nucleoside/nucleotide inhibitor sites in a metal-independent manner. Further characterization, using fluorescence-based thermal denaturation and a crystal structure of the isolated RNase H domain reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mode of this class of molecules. These structures provide a means for structurally guided design of novel RNase H 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

MOLECULAR DYNAMICS, DOCKING, DENSITY FUNCTIONAL, AND ADMET STUDIES OF HIV-1 REVERSE TRANSCRIPTASE INHIBITORS

2006 ◽  
Vol 05 (03) ◽  
pp. 579-586 ◽  
Author(s):  
CARLOS H. T. P. DA SILVA ◽  
IVONE CARVALHO ◽  
CARLTON A. TAFT
Keyword(s):  
Molecular Dynamics ◽  
Reverse Transcriptase ◽  
Active Site ◽  
Density Functional ◽  
Docking Studies ◽  
Reverse Transcriptase Inhibitors ◽  
Hydrogen Bond Interaction ◽  
Receptor Interactions ◽  
Similar Mode ◽  
Hiv 1

Molecular dynamics, density functional with correlation, as well as docking studies of inhibitors of HIV-1 reverse transcriptase (RT) are reported. We propose in this work a novel potential HIV-1 RT inhibitor (RTI), which theoretically appears to bind in a similar mode as other nucleoside reverse transcriptase inhibitors, and in addition, it introduces a new hydrogen bond interaction with Trp229. Our novel RTI has high docking scores and the molecular dynamics studies, as well as the analysis of the ligand-receptor interactions in the active site and the ADMET properties suggest advantages and specificities for this potential RTI.

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
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