Acta Pharmacologica Sinica 2008 December; 29 (12): 1529-1538; doi: 10.1111/j.1745-7254.2008.00907.x

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.

Keywords: 3-nitroquinoline; epidermal growth factor receptor; tyrosine kinase; inhibitor; molecular modeling