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 enzyme responsible for the conversion of nonactive (sulfated) estrone to the active (nonsulfated) estrone]. From the results of the present study, we conclude that the C(17) polar group may not be necessary for inhibitory activity 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 straight chain inhibitors based upon alkyl alcohols, which upon evaluation, have been shown to possess inhibitory activity (e.g., an inhibitor based upon trichloroethanol has been shown to possess 46% inhibition at 0.76mM).