Article
New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations
Registro en:
LEITE, Débora Inácio; et al. New 1,2,3-triazole- based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations. Chem. Biol. Drug. Des., v.92, p.1670–1682, 2018.
1747-0277
10.1111/cbdd.13333
1747-0285
Autor
Leite, Débora Inácio
Fontes, Fábio de Vasconcellos
Bastos, Monica Macedo
Hoelz, Lucas Villas Boas
Bianco, Maria da Conceição Avelino Dias
Oliveira, Andressa Paula de
Silva, Patricia Bernardino da
Silva, Cristiane França da
Batista, Denise da Gama Jean
Gama, Aline Nefertiti Silva da
Peres, Raiza Brandão
Villar, Jose Daniel Figueroa
Soeiro, Maria de Nazaré C.
Boechat, Nubia
Resumen
Chagas disease has spread throughout the world mainly because of the migration of infected individuals. 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 (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole 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' disease. 2030-01-01