Discovery of O6-benzyl glaziovianin A, a potent cytotoxic substance and a potent inhibitor of α,β-tubulin polymerization
| Autor: | Ichiro Hayakawa, Shuya Shioda, Takumi Chinen, Hideo Kigoshi, Takeo Usui, Akira Sakakura, Haruna Ebisu, Taisei Hatanaka |
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| Rok vydání: | 2016 |
| Předmět: |
010405 organic chemistry
Stereochemistry Chemistry organic chemicals Organic Chemistry Clinical Biochemistry Pharmaceutical Science macromolecular substances 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences Microtubule polymerization chemistry.chemical_compound Colchicine binding Drug Discovery Molecular Medicine Cytotoxic T cell Tubulin polymerization Colchicine heterocyclic compounds Cytotoxicity Mode of action Molecular Biology |
| Zdroj: | Bioorganic & Medicinal Chemistry. 24:5639-5645 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2016.09.026 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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