title: The in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis.
abstract: The in-vitro activity of a group of antifungal compounds known to inhibit ergosterol synthesis was investigated against Leishmania donovani grown as intracellular amastigotes in the human leukaemia monocyte cell line, THP-1. Toxicity on the host cells was assessed using the colorimetric MTT assay. Compounds inhibiting 2,3 oxidosqualene lanosterol cyclase; RO 43-3815, RO 43-5955, RO 43-8208, RO 42-6589 and RO 43-0688 displayed high activity with a median effective dose (ED50) of 0.6, 0.9, 3.5, 2.2 and 0.7 mg/L respectively. Of the azole compounds, oxiconazole had an ED50 value of 3.3 mg/L while ketoconazole showed the least activity. The delta-14-reductase and delta-8-delta-7 isomerase inhibitor, amorolfine, gave the highest therapeutic index with an ED50 value of 1.6 mg/L. Most compounds tested had a lower ED50 value than the standard antileishmanial drugs, sodium stibogluconate (5.5 mg Sbv/L) and meglumine antimoniate (3.0 mg Sbv/L) indicating the clean potential of these antifungal compounds in treating leishmaniasis.
authors.affiliation: Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.
authors.forename: A
authors.initials: A
authors.lastname: Gebre-Hiwot
authors.forename: D
authors.initials: D
authors.lastname: Frommel
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004875:Ergosterol / Q000096:biosynthesis*; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D014407:Tumor Cells, Cultured
chemical_list: D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D004875:Ergosterol