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

• Published in: Steroids 1996-12, Vol.61 (12), p.688-696
• Main Authors: Todorović, Nina M., Stefanovic, Milutin, Tinant, Bernard, Declercq, Jean-Paul, Makler, Michael T., S̆olaja, Bogdan A.
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; antimalarial activity; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Cholestanes - chemical synthesis; Cholestanes - chemistry; Cholestanes - pharmacology; gem-dihydroperoxide; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Models, Molecular; molecular mechanics; Molecular Structure; peroxide; Peroxides - chemical synthesis; Peroxides - chemistry; Peroxides - pharmacology; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Steroids - chemistry; tetraoxane
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/S0039-128X(96)00203-6

Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesized starting from 5α- and 5β-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 5β-cholestane-3α,3β-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 IC 50 = 155 nM.