Antileishmanial activities and mechanisms of action of indole-based azoles

Fabrice Pagniez, Hiam Abdala-Valencia, Pascal Marchand, Marc Le Borgne, Guillaume Le Baut, Sylvie Robert-Piessard, Patrice Le Pape*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Two 3-(α-azolylbenzyl)indoles were evaluated against Leishmania amastigotes. Both compounds proved to be very active against intracellular and axenic amastigotes. The IC50 values of the imidazole derivative, PM17, and the triazole analogue, PM19, against L. mexicana axenic amastigotes, were 4.4 ± 0.1 and 6.4 ± 0.1 μM, respectively. Against intracellular amastigotes, PM17 produced a 66% decrease of leishmanial burden at 1 μM and PM19 had an IC50 of 1.3 μM. In a Balb/c mice model of L. major leishmaniasis, administration of PM17 led to a clear-cut parasite burden reduction: 98.9% in the spleen, 79.0% in the liver and 49.9% in the popliteal node draining the cutaneous lesion. As anticipated, it was brought to the fore that PM17 decreases ergosterol biosynthesis leading to membrane fungal cell alterations. Moreover it was proved that this imidazole antifungal agent induces a parasite burden-correlated decrease in interleukine-4 production both in the splenocyte and the popliteal node of the mouse.

Original languageEnglish (US)
Pages (from-to)277-283
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume21
Issue number3
DOIs
StatePublished - Aug 1 2006

Keywords

  • Antileishmanials
  • Azole derivatives
  • Ergosterol
  • Interleukine-4
  • Leishmania

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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