Background: Schistosomiasis is a neglected disease, which affects millions of people in developing
countries. Its treatment relies on a single therapeutic alternative, the praziquantel. This situation
may lead to drug resistance which, in turn, made urgent the need for new antischistosomal agents. Nacylhydrazones
are usually explored as good antimicrobial agents, but the vanillin-related N-acylhydrazones
have never been tested by their antiparasitic potential.
Objective: Herein, we report the synthesis of seven analogues, three of them unpublished, their biological
investigation against Schistosoma mansoni and Target Fishing studies.
Methods: The compounds were synthesized following classical synthetical approaches. The anthelmintic
potential was assessed as well as their cytotoxicity profile. Confocal laser scanning microscopy and target
fishing study were performed to better understand the observed antischistosomal activity.
Results: Compound GPQF-407 exhibited good antischistosomal activity (47.91 µM) with suitable selectivity
index (4.14). Confocal laser scanning microscopy revealed that it triggered severe tegumental destruction
and tubercle disintegration. Target fishing studies pointed out some probable targets, such as the
serine-threonine kinases, dihydroorotate dehydrogenases and carbonic anhydrase II.
Conclusion: The GPQF-407 was revealed to be a promising antischistosomal agent which, besides presenting
the N-acylhydrazone privileged scaffold, also could be easily synthesized on large scales from
commercially available materials.