Econazole Exhibits In Vitro and In Vivo Efficacy Against Leishmania amazonensis

TL;DR

Econazole, an antifungal drug, shows promise in fighting Leishmania amazonensis in both lab and animal studies.

Contribution

This is the first study to demonstrate econazole's efficacy against L. amazonensis in both in vitro and in vivo models.

Findings

Econazole exhibited potent in vitro activity against L. amazonensis promastigotes and amastigotes.

In vivo treatment with econazole reduced lesion size and parasite load in infected mice.

Econazole showed additive effects when combined with miltefosine.

Abstract

Background/Objectives: Cutaneous leishmaniasis (CL) remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and emerging resistance. Repurposing azole antifungals is a promising approach, as they target ergosterol biosynthesis, a pathway also essential in Leishmania spp. This study investigated the antileishmanial potential of econazole through in vitro and in vivo assays. Methods: Econazole activity was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes using MTT and luminescence-based methods. Cytotoxicity in NCTC cells was determined to calculate the selectivity index (SI). Drug interactions with miltefosine were assessed by fixed-ratio isobologram analysis. In vivo efficacy was examined in BALB/c mice infected with L. amazonensis and orally treated with econazole (2.5, 5, or 10 mg/kg/day) for 28 days. Lesion development and parasite burden were monitored. Molecular docking simulations were performed using SwissDock. Results: Econazole showed potent in vitro activity, with EC50 values of 8.9 µM for promastigotes and 11 µM for intracellular amastigotes, and a CC50 of 31 µM. Isobologram analysis revealed additive interactions with miltefosine (ΣFIC 0.5–1.2; mean 0.95). In vivo, econazole reduced lesion size and parasite load, achieving up to 75% reduction at 10 mg/kg/day. Docking results suggested that econazole may inhibit sterol biosynthesis, potentially through interaction with 14α-demethylase. Conclusions: These findings provide the first evidence of econazole activity against L. amazonensis in vitro and in vivo. Its exploratory efficacy and compatibility with miltefosine support further investigation of econazole as a repurposed candidate for CL, including optimization of dosing strategies and combination regimens.

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