The in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis.

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Gebre-Hiwot A, Frommel D

The in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis.

J Antimicrob Chemother. 1993 Dec;32(6):837-42.

PubMed ID

8144423 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Oxiconazole	Lanosterol synthase	Protein	Yeast	Yes	Inhibitor	Details