Multiple Pathways for the Irreversible Inhibition of Steroid Sulfatase with Quinone Methide‐Generating Suicide Inhibitors

Abstract Unexpected inhibition : 2‐ and 4‐mono‐ and difluoromethyl estrone sulfate derivatives are suicide inhibitors of steroid sulfatase (STS). Kinetic studies suggest that inhibition by the monofluoro derivatives is a result of a quinone methide intermediate that reacts with active‐site nucleophiles, whereas the main inhibition pathway of the 4‐difluoromethyl derivative is a result of decomposition of the initial quinone methide to an aldehyde that acts as potent, almost irreversible inhibitor. magnified image