One-Pot Synthesis of Vinca Alkaloids鈥揚homopsin Hybrids
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- 作者：Olga Gherbovet ; Claire Coderch ; Mar铆a Concepci贸n Garc铆a Alvarez ; J茅r么me Bignon ; Sylviane Thoret ; Fran莽oise Gu茅ritte ; Federico Gago ; Fanny Roussi
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：June 26, 2014
- 年：2014
- 卷：57
- 期：12
- 页码：5470-5476
- 全文大小：521K
- ISSN：1520-4804
文摘
Hybrids of vinca alkaloids and phomopsin A have been elaborated with the aim of interfering with the 鈥渧inca site鈥?and the 鈥減eptide site鈥?of the vinca domain in tubulin. They were synthesized by an efficient one-pot procedure that directly links the octahydrophomopsin lateral chain to the velbenamine moiety of 7鈥?homo-anhydrovinblastine. In their modeled complexes with tubulin, these hybrids were found to superimpose nicely on the tubulin-bound structures of vinblastine and phomopsin A. This good matching can account for the fact that two of them are very potent inhibitors of microtubules assembly and are cytotoxic against four cancer cell lines.