Discovering novel 3-nitroquinolines as a new class of anticancer agents.
OBJECTIVE
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 IC50 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.


CONCLUSIONS
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.
Li
Hai-hong
HH
Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Huang
He
H
Zhang
Xiu-hua
XH
Luo
Xiao-min
XM
Lin
Li-ping
LP
Jiang
Hua-liang
HL
Ding
Jian
J
Chen
Kai-xian
KX
Liu
Hong
H
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D045744:Cell Line, Tumor / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009600:Nitroquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009600:Nitroquinolines; D066246:ErbB Receptors