Discovery of O6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of α,β-tubulin polymerization.
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.
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.
Ichiro
I
Hayakawa
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan.
Shuya
S
Shioda
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
Takumi
T
Chinen
Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
Taisei
T
Hatanaka
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
Haruna
H
Ebisu
Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
Akira
A
Sakakura
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.
Takeo
T
Usui
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.
Hideo
H
Kigoshi
D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006367:HeLa Cells; D006801:Humans; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D058105:Polymerization / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*
D007529:Isoflavones; D014404:Tubulin; C521560:glaziovianin A
Cytotoxicity; O(6)-Benzyl glaziovianin A; Structure–activity relationship study; α,β-Tubulin inhibitor