title: Synthesis and biological evaluation of HQCAs with aryl or benzyl substituents on N-1 position as potential HIV-1 integrase inhibitors.
abstract: A series of new 5-hydroxylquinolone-3-carboxylic acids (HQCAs) with various aryl or benzyl substituents on N-1 position were synthesized and evaluated for their anti-HIV activity in C8166 cell culture. Most of the target compounds displayed activity against wide-type HIV-1 in the low micromolar range in infected C8166 cells. The most active compound 5 g exhibited activity against wild-type HIV-1 and HIV-1 mutant virus A17 with an EC(50) value of 3.17 and 17.88 μM, respectively. The biological results and the docking study revealed that the substitution pattern on N-1 position of the quinolone core might contribute to physicochemical properties of HQCAs and resulted in great influence on their antiviral potency.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, PR China.
authors.forename: Qiu-Qin
authors.initials: QQ
authors.lastname: He
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Hai-Qiu
authors.initials: HQ
authors.lastname: Wu
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Gu
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Ma
authors.forename: Liu-Meng
authors.initials: LM
authors.lastname: Yang
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.forename: Fen-Er
authors.initials: FE
authors.lastname: Chen
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D015363:Quinolones; D019427:HIV Integrase