Acid dissociation constant, a potential physicochemical factor in the inhibition of the enzyme estrone sulfatase (ES)

We report the initial results of the synthesis and biochemical evaluation o f a series of aminosulfonate based compounds of phenol and the determinatio n of the pK(a) of the parent phenol in an attempt to investigate the role o f this physicochemical factor in the irreversible inhibition of the enzyme estrone sulfatase (ES). The results of the study show that there is a stron g correlation between the observed pK(a) and inhibitory activity. We postul ate that the stability of the phenoxide ion, as indicated by the acid disso ciation constant, is an important factor in the irreversible inhibition of this enzyme. (C) 2001 Published by Elsevier Science Ltd.