Background: Chagas disease is a public health problem caused by Trypanosoma cruzi.
Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone
derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally,
benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination
of both structures has been taken into account for drug design.
Methods: Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone
(BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic
resonance, and elemental analysis. All compounds were evaluated biologically in vitro against
two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared
with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular
origin of the trypanocidal properties of these derivatives, docking studies were carried out
Results: Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity
against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal
compound showing a LC50
of 0.06 µM against INC-5 strain. However, compound 4 showed the best
activity against both strains (LC50
<30 µM). Theoretical binding modes obtained suggested covalent
binding that could explain their biological activity.
Conclusion: Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options
for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead