title: Synthesis, biological evaluation and molecular modeling studies of N-aryl-2-arylthioacetamides as non-nucleoside HIV-1 reverse transcriptase inhibitors.
abstract: 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 μM). The studies of structure-activity relationship suggested that 1H-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 AutoDock 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.
authors: College of Life Science and Bio-engineering, Beijing University of Technology, Pingleyuan Street No. 100, Chaoyang District, Beijing 100124, China.
authors: Zhu
authors: Z
authors: Xiaohe
authors: Qin
authors: Q
authors: Yu
authors: Yan
authors: Y
authors: Hong
authors: Song
authors: S
authors: Xiuqing
authors: Zhong
authors: Z
authors: Rugang
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry; D013853:Thioacetamide / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014230:Triazoles / Q000737:chemistry
chemical_list: D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; D014230:Triazoles; D013853:Thioacetamide; C029899:imidazole; C062942:2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase