Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains

2018 ◽  
Vol 26 (3) ◽  
pp. 661-674 ◽  
Author(s):  
Anna Maria Monforte ◽  
Laura De Luca ◽  
Maria Rosa Buemi ◽  
Fatima E. Agharbaoui ◽  
Christophe Pannecouque ◽  
...  
Keyword(s):  
Structural Optimization ◽  
Reverse Transcriptase ◽  
Wild Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv 1

scholarly journals Scaffold Hopping in Discovery of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors: From CH(CN)-DABOs to CH(CN)-DAPYs

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1581
Author(s):  
Ting-Ting Li ◽  
Christophe Pannecouque ◽  
Erik De Clercq ◽  
Chun-Lin Zhuang ◽  
Fen-Er Chen
Keyword(s):  
Reverse Transcriptase ◽  
Scaffold Hopping ◽  
Wild Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Single Digit ◽  
Hydrophobic Cavity ◽  
Structure Activity ◽  
Anti Hiv ◽  
Hiv 1

Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds B4 (EC50 = 6 nM) and B6 (EC50 = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC50 values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 μM). The preliminary structure–activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.

Discovery of Novel Benzimidazolones as Potent Non-Nucleoside Reverse Transcriptase Inhibitors Active Against Wild-Type and Mutant HIV-1 Strains.

ChemInform ◽  
2007 ◽  
Vol 38 (34) ◽  
Author(s):  
Maria Letizia Barreca ◽  
Angela Rao ◽  
Laura De Luca ◽  
Nunzio Iraci ◽  
Anna-Maria Monforte ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Wild Type ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv 1

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

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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