| Texto completo | |
| Autor(es): |
Mesquita, Juliana Tonini
;
Dias, Ingrid de Oliveira
;
Tempone, Andre Gustavo
;
Reimao, Juliana Quero
Número total de Autores: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PHARMACEUTICALS; v. 19, n. 1, p. 14-pg., 2026-01-21. |
| Resumo | |
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 mu M for promastigotes and 11 mu M for intracellular amastigotes, and a CC50 of 31 mu M. Isobologram analysis revealed additive interactions with miltefosine (Sigma FIC 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 14 alpha-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. (AU) | |
| Processo FAPESP: | 24/22547-6 - Investigação de Derivados de Tiazóis e Outros Compostos Químicos Promissores com Potencial Anti-Toxoplasma gondii em Modelos Murinos de Toxoplasmose |
| Beneficiário: | Ingrid de Oliveira Dias |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 18/18954-4 - Reposicionamento de fármacos: avaliação de atividade, seletividade e mecanismo de ação de novos candidatos contra Toxoplasma gondii |
| Beneficiário: | Juliana Quero Reimão Dalla Zanna |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 18/10279-6 - Seleção e Otimização de Novos Candidatos a Fármacos para Leishmaniose e Doença de Chagas |
| Beneficiário: | André Gustavo Tempone Cardoso |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |