title: Design, Synthesis, and Biological Evaluation of Novel Benzoyl Diarylamine/ether Derivatives as Potential Anti-HIV-1 Agents.
abstract: A series of benzoyl diarylamine/ether derivatives were designed, synthesized, and evaluated for their activity against human immunodeficiency virus (HIV) in MT-4 cells. Three compounds (3b, 5a, and 6a1) exhibited moderate activities against wild-type (wt) HIV-1 with EC50 values ranging from 11 to 56 μm. Among them, compound 5a was the most potent inhibitor with a novel chemical skeleton, affording a new lead compound for further molecular optimization. An enzyme assay was also implemented to confirm the binding target of the active compounds represented by 6a1. Molecular simulation studies on compound 5a, 6a1, and 7a4 were carried out to understand their binding mode with wt HIV-1 reverse transcriptase (RT) and provided useful information for further rational design of NNRTIs.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Ji'nan, Shandong, China.
authors.forename: Lingzi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Ji'nan, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Ji'nan, Shandong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Pharmacology, School of Medicine, Shandong University, 44 West Culture Road, 250012, Ji'nan, Shandong, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Ji'nan, Shandong, China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D015195:Drug Design; D004986:Ether / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000814:Aniline Compounds; D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D004986:Ether
keywords: HIV-1; NNRTIs; anti-HIV-1 activity; molecular modeling; synthesis