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

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journal contribution
posted on 12.02.2015, 00:00 by Maria V. Papadopoulou, William D. Bloomer, Galina I. Lepesheva, Howard S. Rosenzweig, Marcel Kaiser, Benjamín Aguilera-Venegas, Shane R. Wilkinson, Eric Chatelain, Jean-Robert Ioset
3-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 14α-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.