A novel type of nonsteroidal estrone sulfatase inhibitors.

Madurahydroxylactone (MHL) is a secondary metabolite produced by the soil bacterium Nonomuria rubra and belongs to the family of benzo[a]naphthacenequinones. We report the initial results and structure-activity relationships of our study into a series of thiosemicarbazone derivatives of madurahydroxylactone as potential nonsteroidal inhibitors of the enzyme estrone sulfatase. The most active compound, the cyclohexylthiosemicarbazone, was shown to be a non-competitive inhibitor with a K(i) of 0.35microM. This compound is devoid of estrogenic properties and showed low acute toxicity in the hen's fertile egg screening test.