Synthesis, antiproliferative activity, and structure-activity relationships of 3-aryl-1H-quinolin-4-ones.
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.
Xiao
Zhu-Ping
ZP
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, P.R. China.
Li
Huan-Qiu
HQ
Shi
Lei
L
Lv
Peng-Cheng
PC
Song
Zhong-Cheng
ZC
Zhu
Hai-Liang
HL
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
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D015363:Quinolones; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D005472:Fluorouracil