Effects of a Squalene-2,3-Epoxidase Inhibitor on Propagation and Sterol Biosynthesis of Leishmania Promastigotes and Amastigotes
A new class of antimycotic agents, the allylamines, are fungistatic or fungicidal for many different pathogenic dermatophytes and yeasts. Their primary mode of action is the inhibition of microsomal squalene-2,3-epoxidase, with accumulation of squalene and loss of cellular ergosterol accompanied by inhibition of growth and reproduction1. Cessation of cell growth and loss of viability coincide with the accumulation of squalene in some species (e.g. Candida parapsilosis), while in others (Candida albicans) complete growth inhibition requires the total cessation of ergosterol synthesis and minimum cellular ergosterol content1. The allylamines also demonstrate selective toxicity. Terbinafine SF 86–327, which is being developed for oral administration against systemic fungal infections, has a negligible effect on the squalene-2,3-epoxidase of vertebrate cholesterol biosynthesis at concentrations greater than the maximal serum concentrations that have been recorded in vitro1.
KeywordsCutaneous Leishmaniasis Free Sterol Candida Parapsilosis Sterol Biosynthesis Trypanosoma Brucei
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