Synthesis of thiocolchicine amine derivatives and evaluation of their antiproliferative activity

A series of 22 amine analogs of thiocolchicine were synthesized using the reductive amination reaction. The antiproliferative activities of these compounds were tested against four tumor cell lines as well as one normal cell line. The tested analogs exhibited IC₅₀ values in the nanomolar range accompanied by high selectivity indexes, and most importantly, they were able to break the drug resistance of the human colon adenocarcinoma resistant cell line (LoVo/DX). Also, a correlation between the antiproliferative activity and physicochemical properties of the novel compounds has been found.