Discovery of O6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of α,β-tubulin polymerization

Ichiro Hayakawa, Shuya Shioda, Takumi Chinen, Taisei Hatanaka, Haruna Ebisu, Akira Sakakura, Takeo Usui, Hideo Kigoshi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have discovered O6-benzyl glaziovianin A, which showed stronger inhibition of microtubule polymerization (IC50 = 2.1 μM) than known α,β-tubulin inhibitors, such as colchicine and glaziovianin A. Also, we performed competition binding experiments of O6-benzyl glaziovianin A and revealed that O6-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 O6(α,β-tubulin inhibitor) or O7(γ-tubulin-specific inhibitor) position.

Original languageEnglish
Pages (from-to)5639-5645
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number21
DOIs
Publication statusPublished - 2016

Fingerprint

Tubulin Modulators
Colchicine
Tubulin
Microtubules
Polymerization
Inhibitory Concentration 50
Binding Sites
glaziovianin A
Derivatives

Keywords

  • Cytotoxicity
  • O-Benzyl glaziovianin A
  • Structure–activity relationship study
  • α,β-Tubulin inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Discovery of O6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of α,β-tubulin polymerization. / Hayakawa, Ichiro; Shioda, Shuya; Chinen, Takumi; Hatanaka, Taisei; Ebisu, Haruna; Sakakura, Akira; Usui, Takeo; Kigoshi, Hideo.

In: Bioorganic and Medicinal Chemistry, Vol. 24, No. 21, 2016, p. 5639-5645.

Research output: Contribution to journalArticle

Hayakawa, Ichiro ; Shioda, Shuya ; Chinen, Takumi ; Hatanaka, Taisei ; Ebisu, Haruna ; Sakakura, Akira ; Usui, Takeo ; Kigoshi, Hideo. / Discovery of O6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of α,β-tubulin polymerization. In: Bioorganic and Medicinal Chemistry. 2016 ; Vol. 24, No. 21. pp. 5639-5645.
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AU - Usui, Takeo

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