New benzimidazole-2-urea derivates as tubulin inhibitors
- Bioorg Med Chem Lett. 2014 Sep 1;24(17):4250-3. doi: 10.1016/j.bmcl.2014.07.035.
- 1. College of Pharmacy, Jilin University, Changchun 130021, China.
- 2. Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou 510530, China.
- 3. College of Pharmacy, Jilin University, Changchun 130021, China. Electronic address: [email protected].
- 4. Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou 510530, China. Electronic address: [email protected].
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.