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

Yulia B Malysheva; Sebastien Combes; Diane Allegro; Vincent Peyrot; Paul Knochel; Andrei E Gavryushin; Alexey Yu Fedorov

doi:10.1016/j.bmc.2012.05.072

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

Bioorg Med Chem. 2012 Jul 15;20(14):4271-8. doi: 10.1016/j.bmc.2012.05.072. Epub 2012 Jun 6.

Authors

Yulia B Malysheva¹, Sebastien Combes, Diane Allegro, Vincent Peyrot, Paul Knochel, Andrei E Gavryushin, Alexey Yu Fedorov

Affiliation

¹ Department of Organic Chemistry, Lobachevsky State University of Nizhni Novgorod, 23 Gagarin Avenue, 603950 Nizhni Novgorod, Russian Federation.

PMID: 22739088
DOI: 10.1016/j.bmc.2012.05.072

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / toxicity
Cell Line
Cell Survival / drug effects
Click Chemistry
Colchicine / analogs & derivatives*
Colchicine / chemical synthesis
Colchicine / chemistry
Colchicine / toxicity
Dimerization
Humans
Ligands
Microtubules / chemistry*
Microtubules / metabolism
Protein Binding
Tubulin Modulators / chemical synthesis*
Tubulin Modulators / chemistry
Tubulin Modulators / toxicity

Substances

Antineoplastic Agents
Ligands
Tubulin Modulators
tubulizine A
tubulizine B
Colchicine