title: Design and synthesis of 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives as novel anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase.
abstract: Novel 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives 12a-n were designed and prepared through an intramolecular cyclization reaction and evaluated for in vitro anticancer activity. Among the synthesized compounds, 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) displayed potent cytotoxicity against several different tumor cell lines at a sub-micromolar level. Furthermore, results of fluorescence-activated cell sorting (FACS) analysis suggested that 12e induced cell cycle arrest in the G2/M phase accompanied by apoptosis in HL-60 and H460 cells. This action was confirmed by Hoechst staining and caspase-3 activation. Due to their easy synthesis and remarkable biological activities, 4-phenylquinolin-2(1H)-one analogs (4-PQs) are promising new anticancer leads based on the quinoline scaffold. Accordingly, compound 12e was identified as a new lead compound that merits further optimization and development as an anticancer candidate.
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC.
authors.forename: Yi-Fong
authors.initials: YF
authors.lastname: Chen
authors.forename: Yi-Chien
authors.initials: YC
authors.lastname: Lin
authors.forename: Po-Kai
authors.initials: PK
authors.lastname: Huang
authors.forename: Hsu-Chin
authors.initials: HC
authors.lastname: Chan
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: C586725:6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one; D000970:Antineoplastic Agents; D015363:Quinolones; D053148:Caspase 3
keywords: 4-Phenylquinolin-2(1H)-one (4-PQ); Anticancer agent; Apoptosis; Podophyllotoxin; Structure–activity relationships (SAR)