title: Inhibition of fungal and mammalian sterol biosynthesis by 2-aza-2,3-dihydrosqualene.
abstract: 2-Aza-2,3-dihydrosqualene (I) and a quaternary ammonium derivative (II) inhibited ergosterol biosynthesis in cells and cell-free extracts of the pathogenic yeast Candida albicans as measured by incorporation of radiolabelled precursors. The compounds inhibited squalene epoxidase and 2,3-oxidosqualene cyclase to varying degrees in microsomes from C. albicans and from rat liver. The rat liver epoxidase was 50% inhibited by I at 2.4 microM. In C. albicans cells, but not in cell-free extracts, I also inhibited lanosterol demethylation and led to accumulation of an unidentified polar product.
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004875:Ergosterol / Q000096:biosynthesis*; D019751:Intramolecular Transferases; D007535:Isomerases / Q000037:antagonists & inhibitors; D007810:Lanosterol / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D010105:Oxygenases / Q000037:antagonists & inhibitors; D051381:Rats; D013185:Squalene / Q000031:analogs & derivatives* / Q000494:pharmacology; D050603:Squalene Monooxygenase
chemical_list: D007810:Lanosterol; D013185:Squalene; C039926:2-aza-2-dihydrosqualene; D010105:Oxygenases; D050603:Squalene Monooxygenase; D007535:Isomerases; D019751:Intramolecular Transferases; C021924:lanosterol synthase; D004875:Ergosterol