Synthesis and antiproliferative activity of substituted diazaspiro hydantoins: a structure–activity relationship study

In the course of structure–activity relationship studies and to explore the antiproliferative effect associated with the hydantoin framework, diversely substituted several diazaspiro hydantoins were synthesized. Variation in the functional group at N-terminal of the hydantoin ring and coupling of different substituted aromatic acids in 4-aminocyclohexanone ring led to three sets of compounds. The antiproliferative effect of the compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (NDF-103 skin fibroblast cells) and four human cancer cell lines (MCF-7 breast carcinoma cell line, HepG-2 hepatocellular carcinoma cell line, HeLa cervix carcinoma cell line and HT-29 colon carcinoma cell line) for the time period of 24 h. Among the series, some compounds exhibited interesting growth inhibitory effects against all four cell lines. From the SAR studies, it reveals that, the substitution at N-terminal in hydantoin ring plays key role in the antiproliferative activity.