γ-チューブリン特異的阻害剤　ガタスタチンG2の開発

抄録

Glaziovianin A is an isoflavone derivative isolated from the leaves of Brazilian tree. Glaziovianin A shows antitumor activity and inhibition of α,β-tubulin polymerization. We developed gatastatin, which was O⁷-benzyl glaziovianin A, as a specific inhibitor of γ-tubulin. To the best of our knowledge, gatastatin is the first γ-tubulin-specific inhibitor. Because gatastatin specifically inhibits γ-tubulin, we synthesized O⁶-modified gatastatin for the development of γ-tubulin-specific inhibitor by using oxidative removal of methyl ether group in aromatic ring, as a key step. As results, O⁶-propargyl gatastatin showed strong inhibitory activity against γ-tubulin. We named this compound as “gatastatin G2”. The inhibitory activity against γ-tubulin of gatastatin G2 was stronger than that of gatastatin. This compound would be a useful tool for investigating γ-tubulin function in cells.