Structural insights into the design of indole derivatives as tubulin polymerization inhibitors

FEBS Letters

article

Yuanyuan Li¹  Jiazhen Yang¹  Lu Niu¹  Daojun Hu¹  Huijuan Li¹  Lijuan Chen¹  Yamei Yu¹  Qiang Chen¹ 

[1] Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy

关键词: colchicine binding site;    D64131;    drug design;    indole;    tubulin;   

DOI  :  10.1002/1873-3468.13566

来源: John Wiley & Sons Ltd.

【 摘 要 】

Microtubules are composed of ab-tubulin heterodimers, and drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Small synthetic molecules with an indole nucleus as a core structure have been identified as microtubule inhibitors and recognized as anticancer agents. However, structural information for the interactions between indole derivatives and tubulin is sparse. Here, we present the 2.55 A crystal structure of tubulin in complex with the indole derivative D64131. We compare the binding modes of D64131, colchicine, and five other indole derivatives to tubulin. These results reveal the interactions between the indole derivatives and tubulin, explain previous results of structure-activity-relationship (SAR) studies and, thus, provide insights into the development of new indole derivatives targeting the colchicine binding site.

【 授权许可】

Unknown