Vanillin-related N-acylhydrazones: Synthesis, antischistosomal properties and target fishing studies

Schistosomiasis treatment relies on a single drug, the praziquantel, for which resistance has already being reported1. For this reason, there is an imperative need for new alternatives. Herein we report the synthesis of seven vanillin-related N-acylhydrazones2 and their inhibitory activity3 against Schistosoma mansoni. A target fishing study was also performed4. Anthelmintic potential was assessed by observing changes in motor activity and death of adult male worms, as well as by Confocal Laser Scanning Microscopy (CLSM). Cytotoxicity was determined against Vero cells employing MTT viability assay. Compound GPQF-407 exhibited good inhibitory activity (47.91 µM) with selectivity index of 4.14. CLSM revealed an extensive tegumental destruction after treatment with GPQF-407. Target fishing studies pointed out the Serine-Threonine Kinases, Dihydroorotate Dehydrogenase and Carbonic Anhydrase II as potential targets. In combination, these results disclose N-acylhydrazones as antischistosomal agents, mainly when considering that this scaffold is easily synthesized on large scales from commercially available materials.