A novel type of nonsteroidal estrone sulfatase inhibitors

Bioorg Med Chem Lett. 2002 May 20;12(10):1339-42. doi: 10.1016/s0960-894x(02)00171-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytosine / analogs & derivatives
  • Cytosine / chemical synthesis*
  • Cytosine / pharmacology
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Kinetics
  • Lactones / chemical synthesis*
  • Lactones / pharmacology
  • Naphthacenes / chemical synthesis*
  • Naphthacenes / pharmacology
  • Purines / chemical synthesis*
  • Purines / pharmacology
  • Quinones / chemical synthesis*
  • Quinones / pharmacology
  • Structure-Activity Relationship
  • Sulfatases / antagonists & inhibitors*

Substances

  • 6-methoxypurine
  • Enzyme Inhibitors
  • Lactones
  • Naphthacenes
  • Purines
  • Quinones
  • pseudoisocytosine
  • Cytosine
  • Sulfatases
  • estrone sulfatase