{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:57:03Z","timestamp":1791262623294,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Chagas disease affects more than 10 million people worldwide, and yet, as it has historically been known as a disease of the poor, it remains highly neglected. Two currently available drugs exhibit severe toxicity and low effectiveness, especially in the chronic phase, while new drug discovery has been halted for years as a result of a lack of interest from pharmaceutical companies. Although attempts to repurpose the antifungal drugs posaconazole and ravuconazole (inhibitors of fungal sterol 14\u03b1-demethylase [CYP51]) are finally in progress, development of cheaper and more efficient, preferably\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma cruzi<\/jats:named-content>\n            -specific, chemotherapies would be highly advantageous. We have recently reported that the experimental\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n            CYP51 inhibitor VNI cures with 100% survival and 100% parasitological clearance both acute and chronic murine infections with the Tulahuen strain of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n            . In this work, we further explored the potential of VNI by assaying nitro-derivative-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n            strains, Y and Colombiana, in highly stringent protocols of acute infection. The data show high antiparasitic efficacy of VNI and its derivative (VNI\/VNF) against both forms of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n            that are relevant for mammalian host infection (bloodstream and amastigotes), with the\n            <jats:italic>in vivo<\/jats:italic>\n            potency, at 25 mg\/kg twice a day (b.i.d.), similar to that of benznidazole (100 mg\/kg\/day). Transmission electron microscopy and reverse mutation tests were performed to explore cellular ultrastructural and mutagenic aspects of VNI, respectively. No mutagenic potential could be seen by the Ames test at up to 3.5 \u03bcM, and the main ultrastructural damage induced by VNI in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. cruzi<\/jats:named-content>\n            was related to Golgi apparatus and endoplasmic reticulum organization, with membrane blebs presenting an autophagic phenotype. Thus, these preliminary studies confirm VNI as a very promising trypanocidal drug candidate for Chagas disease therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.00070-13","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T03:04:57Z","timestamp":1371524697000},"page":"4151-4163","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["<i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            Studies of the Antiparasitic Activity of Sterol 14\u03b1-Demethylase (CYP51) Inhibitor VNI against Drug-Resistant Strains of Trypanosoma cruzi"],"prefix":"10.1128","volume":"57","author":[{"given":"Maria de Nazar\u00e9 Correia","family":"Soeiro","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular do IOC, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elen Mello","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular do IOC, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane Fran\u00e7a","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular do IOC, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise da Gama Jaen","family":"Batista","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular do IOC, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Meuser","family":"Batista","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular do IOC, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ, 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