Medicinal Chemistry

Antitumor Activity of Furanoallocolchicinoid-Chitosan Conjugate

Abstract

Elena V Svirshchevskaya, Iuliia A Gracheva, Andrey G Kuznetsov, Ekaterina V Myrsikova, Maria V Grechikhina, Anastasia A Zubareva and Alexey Yu Fedorov

Colchicine irreversibly binds to tubulin, blocks microtubule formation, and inhibits cell division. However, its usage as an antitumor agent is limited due to its distribution to many tissues and low accumulation in the tumor. The increase in molecule weight can change colchicine biodistribution and decrease side effects. The aim of this work was to study in vivo and in vitro antitumor activity of colchicine-chitosan conjugate. A new allocolchicine derivative – furanoallocolchicinoid 3 was synthesized and conjugated to chitosan (4). Both 3 and 4 induced in vitro tubulin reorganization, cell cycle arrest, and inhibition of cell proliferation in 2D and 3D cultures. Antitumor effect of chitosan, 3, and 4 was studied in Wnt-1 breast tumor bearing mice. Conjugate 4 demonstrated significantly better tumor growth inhibition than 3 possibly as a result of a better accumulation in the tumor.