title: Synthesis and antiproliferative evaluation of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives.
abstract: A number of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-6-{4-[3-(dimethylamino)propoxy]phenyl}-2-fluoro-9-hydroxy-11H-indeno[1,2-c]quinolin-11-one O-3-(dimethylamino)propyl oxime (23a) was the most active, exhibited GI(50) values of 0.64, 0.39, 0.55, 0.67, and 0.65μM against the growth of Hep G2, Hep 3B, A549, H1299, and MDA-MB-231, respectively. Compound 23a inhibited the growth of hepatoma cell lines in a dose- and time-dependent manner. The proportion of cells was decreased in the G1 and accumulated in G2/M phase after 12h treatment of 23a, while the hypodiploid (sub-G0/G1 phase) cells increased. Further investigations have shown that 23a induced cell cycle arrest at G2/M phase and induce apoptosis via activation of p53, Bax, and caspase-8 which consequently cause cell death.
authors.affiliation: Department of Medicinal and Applied Chemistry, College of Life Science, and Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.forename: Cherng-Chyi
authors.initials: CC
authors.lastname: Tzeng
authors.forename: Kuin-Yu
authors.initials: KY
authors.lastname: Chung
authors.forename: Chai-Lin
authors.initials: CL
authors.lastname: Kao
authors.forename: Chih-Yao
authors.initials: CY
authors.lastname: Hsu
authors.forename: Chih-Mei
authors.initials: CM
authors.lastname: Cheng
authors.forename: Keng-Shiang
authors.initials: KS
authors.lastname: Huang
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines