Synthesis and antiproliferative screening of novel doubly modified colchicines containing urea, thiourea and guanidine moieties

Abstract

A new series of 10-demethoxy-10-methylaminocolchicines bearing urea, thiourea or aguanidine moieties at position C7 has been designed, synthesized and evaluated for in vitro anticancer activity against different cancer cell lines (A549, MCF-7, LoVo, LoVo/DX). The majority of the new derivatives were active in the nanomolar range and were characterized by lower IC₅₀ values than cisplatin or doxorubicin. Two ureas (4 and 8) and thioureas (19 and 25) were found to be good antiproliferative agents (low IC₅₀ values and high SI) and could prove to be promising candidates for further research in the field of anticancer drugs based on the colchicine skeleton.