ArticleMemorias do Instituto Oswaldo Cruz2025
In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi.
Article in Memorias do Instituto Oswaldo Cruz, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
backgroundThe protozoan Trypanosoma cruzi causes Chagas disease (CD). There are two drugs available for the treatment with limited efficacy, especially in the later stage. Focusing on drug repurposing by virtual screening of chemical databases, butoconazole (BTZ) was identified as promising hit.
objectivesOur aim was to explore the trypanosomicidal effect of BTZ alone or in combination with benznidazole (BZ) against T. cruzi. METHODS AND
findingsOur in vitro assays validated the low cytotoxicity of BTZ and high potency on amastigotes (EC50 = 0.07 μM), being 24-fold more potent than BZ. Washout assays demonstrated the sterilisation capacity of BTZ, whereas its combination with BZ gave an additive interaction (xƩFICI = 0.66). In a mouse model of acute T. cruzi infection, BTZ was unable to suppress parasitaemia but ensured the animal survival. BTZ plus BZ reduced parasitaemia and provided higher survival rates than monotherapies. However, quantitative polymerase chain reaction (qPCR) revealed that BTZ + BZ protocol gave 100% of lack of parasitological cure, as parasite satDNA was amplified in the heart of all surviving animals. MAIN
conclusionsOur dataset reinforces the relevance of drug repurposing and combination strategies to advance into the development of novel therapeutic approaches for CD.
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