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

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 (IC50 = 0.599–2.93 μМ). 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.

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