Structure Optimization of Gatastatin for the Development of γ-Tubulin-Specific Inhibitor.

ABSTRACT: Gatastatin (O ⁷-benzyl glaziovianin A) is a γ-tubulin-specific inhibitor that is used to investigate γ-tubulin function in cells. We have previously reported that the unsubstituted phenyl ring of the O ⁷-benzyl group in gatastatin is important for γ-tubulin inhibition. To obtain further structural information regarding γ-tubulin inhibition, we synthesized several gatastatin derivatives containing a fixed O ⁷-benzyl moiety. Modifications of the B-ring resulted in drastic decrease in cytotoxicity, abnormal spindle formation activity, and inhibition of microtubule (MT) nucleation. In contrast, various O ⁶-alkylated gatastatin derivatives showed potent cytotoxicity, induced abnormal spindle formation, and inhibited MT nucl

SUBMITTER: Shintani K 

PROVIDER: S-EPMC7294552 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature