Design, Synthesis and in vitro Anti-Cancer Activity of Novel Ethyl 4-Oxo-2-iminothiazolidin-5-ylidene Acetates

Abstract

A series of novel ethyl 4-oxo-2-iminothiazolidin-5-ylidene acetate derivatives were synthesized through the three-component coupling annulation of amines, isothiocyanates and diethyl but-2-ynedioates. The obtained compounds were assayed in vitro for their anti-cancer activities against human liver cancer (HepG2) and human breast cancer (MCF-7) cell lines by standard methyl thiazolyl tetrazolium (MTT) method, most of which exhibited significant cytotoxicity. In particular, ethyl (Z)-2-((Z)-2-((3,4-dichlorophenyl)imino)-3-(3-(4-methylpiperazin-1-yl)propyl)-4-oxothiazolidin-5-ylidene)-acetate (4r) displayed the highest level of cytotoxicity compared with cisplatin, and its IC50 values for HepG2 and MCF-7 cells were 0.88 and 0.80 μmol/L, respectively. Their preliminary structure-activity relationship was also discussed. The remarkable cytotoxic nature of these substances against cancer cells could be considered as promising chemotherapeutic agents to be developed in future.