Synthesis of amidinohydrazones and evaluation of their inhibitory effect towards aldosterone synthase (CYP11B2) and the formation of selected steroids

Arch Pharm (Weinheim). 2004 Jul;337(7):411-6. doi: 10.1002/ardp.200400872.

Abstract

The synthesis and biological evaluation of a series of amidinohydrazones (3a-h, 6a-c, 8 and 9) as potential nonsteroidal inhibitors of aldosterone synthase (CYP11B2) are described. The compounds were tested in vitro using CYP11B2-expressing fission yeast; they showed only marginal inhibitory effect. Compound 6c was evaluated for its effect on the formation of aldosterone, cortisol, androstenedione, and DHEA in the adrenocortical tumor cell line NCI-H295R. It exhibited no significant effect on the production of these products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / biosynthesis
  • Amidines / chemical synthesis*
  • Amidines / pharmacology
  • Androstenedione / biosynthesis
  • Cell Line, Tumor
  • Cytochrome P-450 CYP11B2 / antagonists & inhibitors*
  • Dehydroepiandrosterone / biosynthesis
  • Drug Design
  • Humans
  • Hydrazones / chemical synthesis*
  • Hydrazones / pharmacology
  • Hydrocortisone / biosynthesis
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / enzymology
  • Steroids / biosynthesis*

Substances

  • Amidines
  • Hydrazones
  • Steroids
  • Androstenedione
  • Dehydroepiandrosterone
  • Aldosterone
  • Cytochrome P-450 CYP11B2
  • Hydrocortisone