Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10590987 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
Emerging drug resistance and other drawbacks limit tubulin inhibitors' therapeutic applications and developing novel tubulin inhibitors still attracts intensive efforts. We describe the discovery and structure-activity relationship study of a series of benzimidazole-2-urea derivatives as novel β tubulin inhibitors. The representative compound 6o potently suppressed the proliferation of a panel of human cancer cells (NCI-H460, Colo205, K562, A431, HepG2, Hela, MDA-MB-435S) with IC50 values of 0.040, 0.050, 0.006, 0.026, 1.774, 0.452 and 0.052 μM, respectively. Compound 6o obviously inhibited NCI-H460 spindles formation and induced cell cycle arrest at G2/M phase at 0.10 μM. Computational study suggested that 6o interacts with β tubulin in a novel binding mode. Our results suggested that benzimidazole-2-urea derivatives might be promising tubulin inhibitors with novel binding mode for further development.
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Authors
Wenna Wang, Dexin Kong, Huimin Cheng, Li Tan, Zhang Zhang, Xiaoxi Zhuang, Huoyou Long, Yang Zhou, Yong Xu, Xiaohong Yang, Ke Ding,