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 (IC50/24 h = 10.3 mu M) 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 (IC50/96 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.

Automated summary

In this study, a new series of phenoxyacetohydrazones derivatives were designed, synthesized, and evaluated for their antitrypanosomal and cytotoxic activities. Compound 11 showed activity against trypomastigotes equivalent to benznidazole, while compound 19 exhibited significantly higher activity against infected cultures compared to the standard drug.