Discovery of O-6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of alpha,beta-tubulin polymerization

作者：Hayakawa Ichiro^*; Shioda Shuya; Chinen Takumi; Hatanaka Taisei; Ebisu Haruna; Sakakura Akira; Usui Takeo^*; Kigoshi Hideo^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(21): 5639-5645.

DOI：10.1016/j.bmc.2016.09.026

• O-6-Benzyl glaziovianin A
• Cytotoxicity
• alpha,beta-Tubulin inhibitor
• Structure-activity relationship study

We have discovered O-6-benzyl glaziovianin A, which showed stronger inhibition of microtubule polymerization (IC50 = 2.1 mu M) than known alpha,beta-tubulin inhibitors, such as colchicine and glaziovianin A. Also, we performed competition binding experiments of O-6-benzyl glaziovianin A and revealed that O-6-benzyl glaziovianin A binds to the colchicine binding site with high affinity. It is interesting that glaziovianin A derivatives change their mode of action in benzylation at the O-6 (alpha,beta-tubulin inhibitor) or O-7 (gamma-tubulin-specific inhibitor) position.

• 出版日期2016-11-1