Open AccessDiscovering novel 3‐nitroquinolines as a new class of anticancer agents 1
Author(s) -
LI Haihong,
HUANG He,
ZHANG Xiuhua,
LUO Xiaomin,
LIN Liping,
JIANG Hualiang,
DING Jian,
CHEN Kaixian,
LIU Hong
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00907.x
Subject(s) - sulforhodamine b , quinoline , cell culture , chemistry , epidermal growth factor receptor , kinase , epidermoid carcinoma , cancer research , a431 cells , growth inhibition , cell growth , cancer , pharmacology , biochemistry , in vitro , cell , cytotoxicity , biology , receptor , medicine , cell cycle , genetics , molecular medicine , organic chemistry
Aim: To design and synthesize a novel class of antitumor agents, featuring the 3‐nitroquinoline framework. Methods: Based on the enzyme‐binding features of Ekb1, introducing a nitro group at the 3‐position of the quinoline core, a series of novel 3‐nitroquinolines was designed and synthesized. The inhibition of epidermal growth factor receptor (EGFR) activity by these compounds was evaluated and analyzed by the sulforhodamine B assay for their inhibitory activities toward human epidermoid carcinoma (A431) cells and breast cancer (MDA‐MB‐468) cells, which are known to overexpress the EGFR kinase. Results: A series of novel 3‐nitroquinoline derivatives were synthesized and evaluated for their antiproliferative effect against the EGFR‐overexpressing tumor cell lines. Several compounds for concentration‐response studies showed prominent inhibitory activities with IC 50 values in the micromolar or nanomolar range. The structure‐activity relationship was discussed in terms of the inhibitory activity against the proliferation of 2 human carcinoma cell lines. Conclusion: This study was the first to identify new structural types of antiproliferative agents against the EGFR‐overexpressing tumor cell lines by the incorporation of the nitro group at the 3‐position of the quinoline core structure, providing promising new templates for the further development of anticancer agents.