作者
Qinhuai Lai, Yuxi Wang, Ruixue Wang, Weirong Lai, Liangze Tang, Yiran Tao, Yu Liu, Ruirui Zhang, Luyi Huang, Haotian Xiang, Shaoxue Zeng, Lantu Gou, Hao Chen, Yuqin Yao, Jinliang Yang
发表日期
2018/8/5
期刊
European Journal of Medicinal Chemistry
卷号
156
页码范围
162-179
出版商
Elsevier Masson
简介
Tubulin inhibitors that target the colchicine binding site continue to emerge as promising anticancer agents. In this study, based on the anti-proliferative activities, a novel tubulin inhibitor 7a3 targeting the colchicine binding site was designed, synthesized, and optimized from a series of novel cis-restricted pyrazole analogues of combretastatin A-4. The structure-activity relationships (SARs) of these newly synthesized compounds are summarized indicating that the methyl substituent at the N1 position and deamination were significantly important for the anti-proliferative efficacy. The optimized compound 7a3 exhibited the ability to arrest the cell cycle in the G2/M phase, induce cell apoptosis, and inhibit cell migration in tumour cells. The results of the immunofluorescence analysis using confocal microscopy and the tubulin polymerization assay revealed that tubulin assembly was disrupted by 7a3 in vitro. Furthermore …
学术搜索中的文章
Q Lai, Y Wang, R Wang, W Lai, L Tang, Y Tao, Y Liu… - European Journal of Medicinal Chemistry, 2018