{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:46:58Z","timestamp":1780332418684,"version":"3.54.1"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo State Research Foundation","doi-asserted-by":"publisher","award":["2018\/10279-6"],"award-info":[{"award-number":["2018\/10279-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo State Research Foundation","doi-asserted-by":"publisher","award":["2018\/18954-4"],"award-info":[{"award-number":["2018\/18954-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Coordenac\u0327\u00e3o de Aperfeic\u0327oamento de Pessoal de N\u00edvel Superior (CAPES) and FAPESP","doi-asserted-by":"publisher","award":["2024\/22547-6"],"award-info":[{"award-number":["2024\/22547-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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 \u00b5M for promastigotes and 11 \u00b5M for intracellular amastigotes, and a CC50 of 31 \u00b5M. Isobologram analysis revealed additive interactions with miltefosine (\u03a3FIC 0.5\u20131.2; 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 14\u03b1-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.<\/jats:p>","DOI":"10.3390\/ph19010185","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:11:17Z","timestamp":1768993877000},"page":"185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Econazole Exhibits In Vitro and In Vivo Efficacy Against Leishmania amazonensis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-3400","authenticated-orcid":false,"given":"Juliana Tonini","family":"Mesquita","sequence":"first","affiliation":[{"name":"Pathophysiology Laboratory, Instituto Butantan, S\u00e3o Paulo 01246-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-0749","authenticated-orcid":false,"given":"Ingrid de Oliveira","family":"Dias","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (PARASITTOS), Faculdade de Medicina de Jundia\u00ed, Jundia\u00ed 13202-550, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre Gustavo","family":"Tempone","sequence":"additional","affiliation":[{"name":"Pathophysiology Laboratory, Instituto Butantan, S\u00e3o Paulo 01246-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4418-0838","authenticated-orcid":false,"given":"Juliana Quero","family":"Reim\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Assays and Research of Alternative Sources of Innovative Therapy for Toxoplasmosis and Other Sicknesses (PARASITTOS), Faculdade de Medicina de Jundia\u00ed, Jundia\u00ed 13202-550, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"ref_1","first-page":"28","article-title":"An overview of the treatment of cutaneous leishmaniasis","volume":"9","author":"Arenas","year":"2020","journal-title":"Fac. 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