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 (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.
Department of Organic Chemistry, Lobachevsky State University of Nizhni Novgorod, 23 Gagarin Avenue, 603950 Nizhni Novgorod, Russian Federation.
Yulia B
YB
Malysheva
Sebastien
S
Combes
Diane
D
Allegro
Vincent
V
Peyrot
Paul
P
Knochel
Andrei E
AE
Gavryushin
Alexey Yu
AY
Fedorov
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D019281:Dimerization; D006801:Humans; D008024:Ligands; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
D000970:Antineoplastic Agents; D008024:Ligands; D050257:Tubulin Modulators; C575845:tubulizine A; C575846:tubulizine B; D003078:Colchicine