2. Academic Validation
  3. Discovery of O6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of α,β-tubulin polymerization

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

  • Bioorg Med Chem. 2016 Nov 1;24(21):5639-5645. doi: 10.1016/j.bmc.2016.09.026.
Ichiro Hayakawa 1,  Shuya Shioda 2,  Takumi Chinen 3,  Taisei Hatanaka 4,  Haruna Ebisu 3,  Akira Sakakura 4,  Takeo Usui 5,  Hideo Kigoshi 6
Affiliations

Affiliations

  • 1 Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. Electronic address: ichiro.hayakawa@okayama-u.ac.jp.
  • 2 Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan.
  • 3 Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
  • 4 Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
  • 5 Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan. Electronic address: usui.takeo.kb@u.tsukuba.ac.jp.
  • 6 Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. Electronic address: kigoshi@chem.tsukuba.ac.jp.
PMID: 27665177 DOI: 10.1016/j.bmc.2016.09.026
Abstract

We have discovered O6-benzyl glaziovianin A, which showed stronger inhibition of microtubule polymerization (IC50=2.1μM) 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.

Keywords

Cytotoxicity; O(6)-Benzyl glaziovianin A; Structure–activity relationship study; α,β-Tubulin inhibitor.

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