Synthesis and antiproliferative evaluation of novel benzoimidazole-contained oxazole-bridged analogs of combretastatin A-4.

Jie Zhou, Jing Jin, Yi Zhang, Yuwen Yin, Xiaoguang Chen, Bailing Xu

Index: Eur. J. Med. Chem. 68 , 222-32, (2013)

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Abstract

A series of novel oxazole-bridged analogs of combretastatin A-4 bearing a benzo[d]-imidazole as B ring were synthesized and evaluated for antiproliferative activities against five human cancer cell lines. Among all the synthesized compounds, the N-unsubstituted benzoimidazole analog 5 and the analogs 6b, 7a and 7b with a small hydrophobic group on nitrogen atom of benzoimidazole ring were identified as the most potent inhibitors of tumor cell growth with IC50 values at nanomolar levels (5, IC50=8.4 nM, HT29; 6b, 7a, 7b, IC50=9.6 nM, 3.8 nM, 3.0 nM, A549). In a murine H22 tumor xenograft model, compound 5 exhibited significant antitumor activity. The binding mode of compound 5 in the colchicine binding site of tubulin was probed.Copyright © 2013 Elsevier Masson SAS. All rights reserved.