Phenoxyacetohydrazones against Trypanosoma cruzi

Herein, we reported the design, synthesis, antitrypanosomal and cytotoxic evaluation of a new phenoxyacetohydrazones series. All derivatives were assayed against bloodstream trypomastigote forms of T. cruzi ( Y strain) and intracellular amastigotes using the model of L-929 cells infected with trypomastigotes of the Tulahuen strain. Compound ( E )- N ′-(3.4-dihydroxybenzylidene)-2-phenoxyacetohydrazide (11) showed activity against trypomastigotes (IC 50 /24 h = 10.3 µM) equivalent to that of benznidazole and with selectivity index (SI) = 46. Against infected cultures, ( E )- N ′-((5-nitrofuran-2-yl) methylene)-2-phenoxyacetohydrazide (19) was active at the nanomolar range (IC 50 /96 h = 40 nM), being about 38-fold more active than the standard drug and with SI equal to 2500. Thus, derivatives 11 and 19 could be considered a good prototypes for the development of new candidates for Chagas disease therapy.