Abstract

The synthesis and biochemical evaluation of a series of esters of 4- sulfamoylated cinnamic acid as potential inhibitors of the enzyme estrone sulfatase (ES) is reported. The results of the study show that the esters of trans 4-sulfamoylated cinnamic acid are weaker irreversible inhibitors of ES in comparison to 4- methylcoumarin-7-O-sulfamate (COUMATE) and its tricyclic derivatives such as 667- COUMATE, as well as the steroidal inhibitor estrone-3-O-sulfamate (EMATE). Structureactivity relationship determination indicates that the flexible nature of the cinnamic acid backbone results in these compounds possessing greatly reduced inhibitory activity compared to the corresponding coumarin derivative. Furthermore, from the superimpositioning of the synthesised compounds onto the substrate, we propose that steric hindrance is an important factor which results in a marked decrease in the inhibitory activity within the large alkyl chain containing compounds.

Keywords: Enzyme Estrone Sulfatase, 4-methylcoumarin-7-O-sulfamate, sulfamoylated cinnamic acid, estrone-3-O-sulfamate