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Synthesis, Antiproliferative Activity, and Structure–Activity Relationships of 3‐Aryl‐1 H ‐quinolin‐4‐ones
Author(s) -
Xiao ZhuPing,
Li HuanQiu,
Shi Lei,
Lv PengCheng,
Song ZhongCheng,
Zhu HaiLiang
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800057
Subject(s) - cytotoxicity , pharmacophore , aryl , chemistry , stereochemistry , cell culture , cancer cell lines , in vitro , cell growth , tyrosine kinase , genistein , structure–activity relationship , cytotoxic t cell , epidermal growth factor receptor , apoptosis , growth inhibition , cancer cell , biochemistry , receptor , cancer , biology , medicine , alkyl , organic chemistry , endocrinology , genetics
The antiproliferative activities of 36 3‐aryl‐1 H ‐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.