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 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. 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.