{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:46:06Z","timestamp":1792190766469,"version":"4.4.0"},"reference-count":33,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["2021-0404"],"award-info":[{"award-number":["2021-0404"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FIOCRUZ","award":["2021-0404"],"award-info":[{"award-number":["2021-0404"]}]},{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"crossref","award":["2021-0404"],"award-info":[{"award-number":["2021-0404"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021778","name":"Agencia I+D+I","doi-asserted-by":"crossref","award":["2021-0404"],"award-info":[{"award-number":["2021-0404"]}],"id":[{"id":"10.13039\/501100021778","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mem. Inst. Oswaldo Cruz"],"abstract":"<jats:p>BACKGROUND  The 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.  OBJECTIVES  Our aim was to explore the trypanosomicidal effect of BTZ alone or in combination with benznidazole (BZ) against T. cruzi.  METHODS and FINDINGS  Our in vitro assays validated the low cytotoxicity of BTZ and high potency on amastigotes (EC50 = 0.07 \u03bcM), being 24-fold more potent than BZ. Washout assays demonstrated the sterilisation capacity of BTZ, whereas its combination with BZ gave an additive interaction (x\u01a9FICI = 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 CONCLUSIONS  Our dataset reinforces the relevance of drug repurposing and combination strategies to advance into the development of novel therapeutic approaches for CD.<\/jats:p>","DOI":"10.1590\/0074-02760240234","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T15:02:40Z","timestamp":1761318160000},"source":"Crossref","is-referenced-by-count":2,"title":["In vitro and in vivo studies on the activity and selectivity of butoconazole in experimental infection by Trypanosoma cruzi"],"prefix":"10.1590","volume":"120","author":[{"given":"Gabriela Rodrigues","family":"Leite","sequence":"first","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise da Gama Jaen","family":"Batista","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Meuser","family":"Batista","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krislayne Nunes","family":"da Costa","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s Mac","family":"Loughlin","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas,  Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia M","family":"Barrionuevo","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas,  Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Talevi","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas,  Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas N","family":"Aberca","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas,  Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otacilio C","family":"Moreira","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Faier-Pereira","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Iandra da Silva","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0078-6106","authenticated-orcid":false,"given":"Maria de Nazar\u00e9 Correia","family":"Soeiro","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz-Fiocruz,  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"issue":"10422","key":"ref1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01787-7","article-title":"Chagas disease","volume":"403","author":"de Sousa AS","year":"2024","journal-title":"Lancet"},{"issue":"10115","key":"ref2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0140-6736(17)31612-4","article-title":"Chagas disease","volume":"391","author":"P\u00e9rez-Molina JA","year":"2018","journal-title":"Lancet"},{"issue":"2","key":"ref3","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s12350-018-1361-1","article-title":"Chagas heart disease a contemporary review","volume":"27","author":"Velasco A","year":"2020","journal-title":"J Nucl 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