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

Abstract 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 (IC 50  = 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.