Design, synthesis and biological evaluation of new aryl thiosemicarbazone as antichagasic candidates

•Twelve thiosemicarbazones were synthesized and assayed against Trypanosoma cruzi.•They were planned as potential inhibitors of cruzain and trypanothione reductase.•The “in vivo” micronucleus test indicated no genotoxic effect of the compounds.•Cruzain inhibition was assessed through docking study and biochemical assay.

The present work reports on the synthesis, biological assaying and docking studies of a series of 12 aryl thiosemicarbazones, which were planned to act over two main enzymes, cruzain and trypanothione reductase. These enzymes are used as targets of trypanocidal activity in Chagas disease control with a minimal mutagenic profile. Three p-nitroaromatic thiosemicarbazones showed high activity against Trypanosoma cruzi in in vitro assays (IC50 < 57 μM), and no mutagenic profile was observed in micronucleous tests. Although the in vitro inhibition test showed that 10-μM doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide