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

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3933-6. doi: 10.1016/j.bmcl.2004.05.069.

Abstract

We present the synthesis of a new family of nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase, designed from flavones and chalcones. Their inhibitory potential was screened on 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta-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 17beta-HSDcl, with IC(50) values in the low micromolar range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • Cinnamates / chemical synthesis*
  • Cinnamates / pharmacology*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Fungi / drug effects
  • Fungi / enzymology*
  • Microbial Sensitivity Tests
  • Models, Biological

Substances

  • Cinnamates
  • Enzyme Inhibitors
  • cinnamic acid
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase