title: Synthesis and antiproliferative evaluation of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers.
abstract: Certain 3-phenylquinolinylchalcone derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-3-(3-(4-methoxyphenyl)quinolin-2-yl)-1-phenylprop-2-en-1-one (6a) and (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one (11) were identified as potential lead compounds for further development. Compound 6a was active against the growth of H1299 and SKBR-3 with IC(50) values of 1.41 and 0.70 μM respectively which was more active than the positive topotecan (IC(50) values of 6.02 and 8.91 μM respectively). Compound 11 exhibited an IC(50) value of less than 0.10 μM against the growth of MDA-MB231, and non-cytotoxic to the normal mammary epithelial cell (H184B5F5/M10). Mechanism studies indicated that compound 11 induced cell cycle arrest at G2/M phase followed by activation of caspase-3, cleavage of PARP, and consequently caused the cell death.
authors.affiliation: Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Tseng
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Chih-Yao
authors.initials: CY
authors.lastname: Hsu
authors.forename: Tzu-Chiang
authors.initials: TC
authors.lastname: Chen
authors.forename: Chih-Mei
authors.initials: CM
authors.lastname: Cheng
authors.forename: Hsien-Cheng
authors.initials: HC
authors.lastname: Tso
authors.forename: Yan-Jia
authors.initials: YJ
authors.lastname: Lu
authors.forename: Cherng-Chyi
authors.initials: CC
authors.lastname: Tzeng
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002599:Chalcone / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D011804:Quinolines; D002599:Chalcone