Structure-activity relationship study of steroidal and nonsteroidal inhibitors of the enzyme estrone sulfatase

We report the initial results of a series of molecular modelling studies to investigate the structural properties of non-steroidal inhibitors required for inhibitory activity against the enzyme estrone sulfatase (ES) [the enz yme responsible for the conversion of nonactive (sulfated) estrone to the a ctive (nonsulfated) estrone], From the results of the present study, we con clude that the C(17) polar group may not be necessary for inhibitory activi ty and that the only requirement appears to be the mimicking of the steroid C(3) sulfonate group. To test our hypotheses, we have designed novel strai ght chain inhibitors based upon alkyl alcohols, which upon evaluation, have been shown to possess inhibitory activity (e.g., an inhibitor based upon t richloroethanol has been shown to possess 46% inhibition at 0.76 mM). (C) 1 999 Academic Press.