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Inhibition of fungal and mammalian sterol biosynthesis by 2‐aza‐2,3‐dihydrosqualene
Author(s) -
Ryder Neil S.,
Dupont Marie-Claude,
Frank Ingeborg
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)80819-5
Subject(s) - squalene monooxygenase , lanosterol , candida albicans , biosynthesis , biochemistry , ergosterol , sterol , demethylation , squalene , yeast , chemistry , microsome , corpus albicans , biology , stereochemistry , microbiology and biotechnology , enzyme , cholesterol , gene , dna methylation , gene expression
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 μM. In C. albicans cells, but not in cell‐free extracts, I also inhibited lanosterol demethylation and led to accumulation of an unidentified polar product.