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Research Article: Synthesis, Biological Evaluation and Molecular Modeling Studies of N ‐aryl‐2‐arylthioacetamides as Non‐nucleoside HIV‐1 Reverse Transcriptase Inhibitors
Author(s) -
Xiaohe Zhu,
Yu Qin,
Hong Yan,
Xiuqing Song,
Rugang Zhong
Publication year - 2010
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2010.01017.x
Subject(s) - reverse transcriptase , chemistry , stereochemistry , moiety , aryl , docking (animal) , nucleoside , autodock , thiourea , molecular model , nucleoside reverse transcriptase inhibitor , reverse transcriptase inhibitor , biochemistry , organic chemistry , rna , medicine , alkyl , nursing , gene , in silico
A series of N ‐aryl‐2‐arylthioacetamide derivatives ( 2 – 4 ) designed as non‐nucleoside reverse transcriptase inhibitors was synthesized and evaluated for their inhibitory activity against HIV‐1 (IIIB) replication in MT‐4 cell cultures. The compounds 2 – 4 were performed by the reaction of thiols and 2‐chloro‐ N ‐substituted‐acetamides and active in the lower micromolar concentration (1.25–20.83 μ m ). The studies of structure–activity relationship suggested that 1 H ‐benzo[ d ]imidazole ring at arylthio moiety strongly improved the anti‐HIV activity and consistent with the experimental data. The results of molecular modeling and docking within the RT non‐nucleoside binding site using A uto D ock confirmed that the 3 series, similar to other non‐nucleoside reverse transcriptase inhibitors such as N ‐(5‐chloro‐2‐pyridinyl)‐ N’ ‐[2‐(4‐ethoxy‐3‐fluoro‐2‐pyridinyl)ethyl]‐thiourea (PETT), was assumed in a butterfly‐like conformation and helped to rationalize some SARs and the biological activity data.