Synthesis and biological evaluation in vitro and in silico of N-propionyl-N'-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi.

ABSTRACT

An N-acylhydrazone scaffold has been used to develop new drugs with diverse biological activities, including trypanocidal activity against different strains of Trypanosoma cruzi. However, their mechanism of action is not clear, although in T. cruzi it has been suggested that the enzyme cruzain is involved. The aim in this work was to obtain new N-propionyl-N'-benzeneacylhydrazone derivatives as potential anti-T. cruzi agents and elucidate their potential mechanism of action by a molecular docking analysis and effects on the expression of the cruzain gene. Compounds 9 and 12 were the most active agents against epimastigotes and compound 5 showed better activity than benznidazole in T. cruzi blood trypomastigotes. Additionally, compounds 9 and 12 significantly increase the expression of the cruzain gene. In summary, the in silico and in vitro data presented herein suggest that compound 9 is a cruzain inhibitor.