title: Synthesis and biological evaluation of (±)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
abstract: A series of (±)-benzhydrol derivatives featuring the essential sulfonamide group at the para position on the C-ring were synthesized and evaluated for the potential anti-HIV activity in C8166 cells. Most of these analogues demonstrated low concentration inhibitory activity with EC(50) values less than 1 μM against the wild-type HIV-1. In particular, compound 7h was identified as the highest active inhibitor of wild-type HIV-1 with an EC(50) value of 0.12 μM and selectivity index value of 312.73. Furthermore, some of them also exhibited moderate activity against the double mutant strain A(17) (K103N+Y181C) with EC(50) values lower than 5 μM. In addition, the binding modes with RT and the preliminary structure-activity relationships of these derivatives were also explored for further chemical modifications.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, PR China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Ma
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Shi-Qiong
authors.initials: SQ
authors.lastname: Yang
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Dai
authors.forename: Liu-Meng
authors.initials: LM
authors.lastname: Yang
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Gu
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.forename: Qiu-Qin
authors.initials: QQ
authors.lastname: He
authors.forename: Fen-Er
authors.initials: FE
authors.lastname: Chen
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D015497:HIV-1; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D001559:Benzhydryl Compounds; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C020225:benzohydrol