title: Synthesis, antiproliferative activity, and structure-activity relationships of 3-aryl-1H-quinolin-4-ones.
abstract: The antiproliferative activities of 36 3-aryl-1H-quinolin-4-ones were determined against two cancer cell lines (Hep G2 and KB) in vitro. The results indicate that most of these compounds show good cytotoxic activity against human cancer cell lines, but no cytotoxicity against a human normal cell line (L02). The positive control compounds genistein and 5-fluorouracil show no selectivity at inhibiting the growth of the above three cell lines. Generally, compounds that bear a halogen atom at the 8 position and a methoxy group at the 3' position exhibited remarkable cytotoxicity toward human cancer cell lines. Electron-withdrawing substituents at the 6 position decrease the antiproliferative activity significantly. We also put forward a pharmacophore model for 3-aryl-4-quinolinones binding with epidermal growth factor receptor protein tyrosine kinases (EGFR PTK). Out of the 36 synthetic compounds, 34 are reported for the first time.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, P.R. China.
authors.forename: Zhu-Ping
authors.initials: ZP
authors.lastname: Xiao
authors.forename: Huan-Qiu
authors.initials: HQ
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Lv
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Song
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005472:Fluorouracil / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007624:KB Cells; D008099:Liver / Q000166:cytology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D015363:Quinolones; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D005472:Fluorouracil