title: Design, synthesis, and biological evaluation of novel γ-carboline ketones as anticancer agents.
abstract: A series of novel γ-carboline ketones were designed, synthesized and evaluated for their cytotoxic activity in vitro against six human cancer cell lines (A549, SGC, HCT116, MCF-7, K562 and K562R). Biological evaluation revealed that almost all of the new compounds displayed moderate to potent cytotoxic activities against the tested cells. Among them, seven of the fourteen new compounds show more potent cytotoxic activities against K562R cell line than that of the positive control, taxol. Primary mechanism research on the most potent compound 6f indicated that it was a potent tubulin polymerization inhibitor, with IC(50) value of 4.3 μM, equivalent to that of CA-4, and arresting cell cycle in G(2)/M phase.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053 Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.forename: Jianshu
authors.initials: J
authors.lastname: Lou
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: He
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D014404:Tubulin