Design, synthesis and biological evaluation of novel carbamodithioates as anti-proliferative agents against human cancer cells

A series of new carbamodithioates compounds has been successfully synthesized. All the carbamodithioate derivatives of SFE and SFA with benzenethiols (substituted or unsubstituted) exhibited, in general, higher percentages of inhibition than their parent compounds: SFE and SFA. A number of carbamodithioate derivatives with benzenethiols (substituted or unsubstituted) (1l, 1m, 1n, 1o, 1q, 1s, 2l, 2n, 2p, 2q, 2r and 2s) were investigated for in vitro anti-proliferative activities against five cancer cell lines: SMMC-7721, A549, A375, Ha 116 and Hela. The carbamodithioate compounds (1l, 1m, 1n, 1o, 1q and 1s) derived from SFE and the carbamodithioate compounds (2l, 2n, 2p, 2q, 2r and 2s) derived from SFA are more sensitive toward SMMC-7721 and A549 cancer cells than toward other cancer cells in that their IC50 values are appreciably lower. Moreover, they exhibited stronger inhibitory activities than their parent compound SFE and SFE. Further investigation indicated that these carbamodithioate derivatives inhibited colony formation of SMMC-7721 and remarkably induced the G2/M or G0/G1 phase cell cycle arrest and apoptosis in SMMC-7721 cancer cells. More important, these carbamodithioate derivatives are stable in protic solvent media than their parent compounds. By virtue of the simplicity of the preparation of these carbamodithioate derivatives and their stability, compounds (1m) under bar and (2s) under bar could be the promising candidates for replacement for their parent SFE and SFA for cancer prevention agents. (C) 2018 Elsevier Masson SAS. All rights reserved.