Oxygen binding isotope effects of triazole-based HIV-1 reverse transcriptase inhibitors indicate the actual binding site

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.

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Arylazolylthioacetanilide. Part 11: Design, Synthesis and Biological Evaluation of 1,2,4-triazole Thioacetanilide Derivatives as Novel Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

Medicinal Chemistry ◽

10.2174/1573406411309070010 ◽

2013 ◽

Vol 9 (7) ◽

pp. 968-973 ◽

Cited By ~ 9

Author(s):

Zhenyu Li ◽

Yuan Cao ◽

Peng Zhan ◽

Christophe Pannecouque ◽

Jan Balzarini ◽

...

Keyword(s):

Reverse Transcriptase ◽

Biological Evaluation ◽

Reverse Transcriptase Inhibitors ◽

Design Synthesis ◽

Synthesis And Biological Evaluation ◽

Hiv 1

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(Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes.

Journal of Virology ◽

10.1128/jvi.70.6.3698-3705.1996 ◽

1996 ◽

Vol 70 (6) ◽

pp. 3698-3705 ◽

Cited By ~ 22

Author(s):

R A Olmsted ◽

D E Slade ◽

L A Kopta ◽

S M Poppe ◽

T J Poel ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Reverse Transcriptase ◽

Human Immunodeficiency Virus Type ◽

Broad Spectrum ◽

Drug Resistant ◽

Reverse Transcriptase Inhibitors ◽

Nonnucleoside Reverse Transcriptase Inhibitors ◽

Immunodeficiency Virus ◽

Hiv 1

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An insight on promising strategies hoping to cure HIV-1 infection by targeting Rev protein—short review

Pharmacological Reports ◽

10.1007/s43440-021-00257-9 ◽

2021 ◽

Author(s):

Sahana Pai ◽

Jayesh Mudgal ◽

B. Venkatesh Kamath ◽

K. Sreedhara Ranganath Pai

Keyword(s):

Reverse Transcriptase ◽

Regulatory Protein ◽

Short Review ◽

Fixed Dose ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Promising Therapeutic Target ◽

Latent Hiv ◽

Approved Drugs ◽

Hiv 1

AbstractHuman immunodeficiency virus-1 (HIV-1) infection remains to be one of the major threats throughout the world. Many researchers are working in this area to find a cure for HIV-1. The group of the FDA approved drugs which are currently used against HIV-1 in the clinical practice include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors (InIs), and protease inhibitors (PIs). Fixed dose combinations (FDCs) of these drugs are available and are used as per the anti-retroviral therapy (ART) guidelines. Despite these, unfortunately, there is no cure for HIV1 infection to date. The present review is focused upon describing the importance of a post-transcriptional regulatory protein “Rev”, responsible for latent HIV-1 infection as a possible, and promising therapeutic target against HIV-1.

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