Work

Econazole Exhibits In Vitro and In Vivo Efficacy Against Leishmania amazonensis

Year: 2026

Type: article

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.

Source: Pharmaceuticals

DOI: 10.3390/ph19010185

Authors: Juliana Tonini Mesquita, Ingrid de Oliveira Dias, Andre Gustavo Tempone, Juliana Quero Reimão

Institutions: Instituto Butantan, Faculdade de Medicina de Jundiaí

Language: English

Topic: Research on Leishmaniasis Studies

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499