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In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (<jats:bold>3\u20138<\/jats:bold>). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3\u2010triazole ring. All the compounds were synthesized in good yields. With the exception of compound <jats:bold>7<\/jats:bold>, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds <jats:bold>3<\/jats:bold>,<jats:bold> 4<\/jats:bold>,<jats:bold> 5<\/jats:bold>, and <jats:bold>8<\/jats:bold> were active against trypomastigote. Compounds <jats:bold>4<\/jats:bold> and <jats:bold>5<\/jats:bold> showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, <jats:bold>3\u20138<\/jats:bold> showed lower potency and higher toxicity than Bnz. Although the 1,2,3\u2010triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas\u2019 disease.<\/jats:p>","DOI":"10.1111\/cbdd.13333","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T03:54:03Z","timestamp":1525924443000},"page":"1670-1682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["New 1,2,3\u2010triazole\u2010based analogues of benznidazole for use against <i>Trypanosoma cruzi<\/i> infection: In vitro and in vivo evaluations"],"prefix":"10.1111","volume":"92","author":[{"given":"D\u00e9bora In\u00e1cio","family":"Leite","sequence":"first","affiliation":[{"name":"Departamento de Sintese de Farmacos Instituto de Tecnologia em Farmacos Farmanguinhos \u2010 Fiocruz Fundacao Oswaldo Cruz  Rio de Janeiro Brazil"},{"name":"Programa de Pos\u2010Gradua\u00e7\u00e3o em Farmacologia e Quimica Medicinal do Instituto de Ciencias Biomedicas \u2013 ICB\u2010 UFRJ Centro de 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