Design and synthesis of 14 alpha-methyl-15-aza-D-homosterols as novel antimycotics

J Med Chem. 1990 Feb;33(2):877-80. doi: 10.1021/jm00164a065.

Abstract

A novel series of 14 alpha-methyl-15-aza-D-homosterols 3-7 has been synthesized. These compounds display significant antimycotic activity in vitro (MIC = 0.8-3.1 micrograms/mL) that compares quite favorably to the activity observed for fluconazole (MIC = 0.8 micrograms/mL). Azasterols 3 and 4 were active in vivo as reflected in the increased survival time of Candida albicans infected mice. The antimycotic activity of 3-7 is hypothesized to be a consequence of the inhibition of fungal 14,15-sterol reductase.

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis*
  • Candidiasis / drug therapy
  • Chemical Phenomena
  • Chemistry, Physical
  • Drug Design
  • Mice
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • Oxidoreductases / antagonists & inhibitors
  • Sterols / chemical synthesis*
  • Sterols / pharmacology

Substances

  • Antifungal Agents
  • Sterols
  • Oxidoreductases
  • delta(14)-sterol reductase
  • NADH, NADPH Oxidoreductases