Cinnamic acid esters as potent inhibitors of fungal 17β-hydroxysteroid dehydrogenase––a model enzyme of the short-chain dehydrogenase/reductase superfamily

We present the synthesis of a new family of nonsteroidal inhibitors of 17β-hydroxysteroid dehydrogenase, designed from flavones and chalcones. Their inhibitory potential was screened on 17β-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17β-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. In a series of cinnamates and related coumarin-3-carboxylates, a number of compounds proved to be potent inhibitors of both the oxidative and reductive reactions catalyzed by 17β-HSDcl, with IC50 values in the low micromolar range.