Novel 3‑Nitrotriazole-Based Amides and Carbinols as Bifunctional Antichagasic Agents

Artículo de publicación ISI3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14a-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed.FONDECYT Postdoctorado 3130364Radiation Medicine Department at NorthShore University HealthSystem NIH GM067871 DNDi Department for Internationl Development (DFID), U.K. Bill & Melinda Gates Foundation (BMGF), USA Reconstruction Credit Institution-Federal Ministry of Education and Research (KfW-BMBF), Germany Directorate-General for International Cooperation (DGIS), The Netherlands FONDECYT Postdoctorado 313036