Steroidal geminal dihydroperoxides and 1,2,4,5-tetraoxanes: structure determination and their antimalarial activity

Steroids. 1996 Dec;61(12):688-96. doi: 10.1016/s0039-128x(96)00203-6.

Abstract

Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesized starting from 5 alpha- and 5 beta-cholestan-3-ones by acid-catalyzed addition of hydrogen peroxide to the ketone. They were characterized by IR, NMR, and mass spectroscopy analysis aided by molecular mechanics calculations, and, in the instance of 5 beta-cholestane-3 alpha,3 beta-dihydroperoxide (6), by x-ray analysis. The synthesized compounds were tested in vitro against Plasmodium falciparum Sierra Leone (D6) and Indochina (W2) malaria clones. All compounds were inactive to both clones, with the exception of tetraoxane 7a, which exhibited modest activity toward D6 clone with IC50 = 155 nM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Cholestanes / chemical synthesis*
  • Cholestanes / chemistry*
  • Cholestanes / pharmacology
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Structure
  • Peroxides / chemical synthesis
  • Peroxides / chemistry*
  • Peroxides / pharmacology
  • Plasmodium falciparum / drug effects
  • Steroids / chemistry

Substances

  • Antimalarials
  • Cholestanes
  • Peroxides
  • Steroids