THE IN-VITRO ANTILEISHMANIAL ACTIVITY OF INHIBITORS OF ERGOSTEROL BIOSYNTHESIS

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 Δ-14-reductase and Δ-8-Δ-7isomerase 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. © 1993 The British Society for Antimicrobial Chemotherapy.