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

A new series of 10-demethoxy-10-methylaminocolchicines bearing urea, thiourea or a guanidine 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.

Automated summary

A new series of 10-demethoxy-10-methylaminocolchicines with urea, thiourea or guanidine moieties at position C7 have been designed, synthesized and evaluated for in vitro anticancer activity. Most of the new derivatives showed promising anticancer activity in the nanomolar range, with lower IC50 values compared to cisplatin or doxorubicin. Specifically, two ureas and two thioureas displayed good antiproliferative effects, making them potential candidates for further research in the field of anticancer drugs based on the colchicine skeleton.