Synthesis and biological evaluation of novel anticancer bivalent colchicine-tubulizine hybrids

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• 作者：Yulia B. Malysheva ; Sebastien Combes ; Diane Allegro ; Vincent Peyrot ; Paul Knochel ; Andrei E. Gavryushin ; Alexey Yu. Fedorov
• 关键词：Hybrid ; Colchicine ; Tubulizine ; Click chemistry ; Cytotoxicity ; Tubulin
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：15 July, 2012
• 年：2012
• 卷：20
• 期：14
• 页码：4271-4278
• 全文大小：416 K

文摘

A series of novel antimitotic hybrids were synthesized in good yields by linking of azide-containing colchicine congeners with acetylene-substituted tubulizine-type derivatives using copper-mediated 1,3-dipolar cycloaddition. Obtained compounds exhibit good cytotoxicity against HBL100 epithelial cell lines (ICb>50b> = 0.599-2.93 ¦Ì§®). Several newly synthesized compounds are the substoichiometric inhibitors of microtubule assembly (R = 0.41-0.78). The results highlight the importance of the length of spacer linking the tubulin binding ligands in heterodimeric molecules.