RESUMO
With the aim of finding new chemical entities based on coumarin and chalcone scaffolds, new hybrid compounds 2-5 were designed and synthesized. The trypanocidal activity of these compounds was tested against the epimastigote, trypomastigote and amastigote stages of the Trypanosoma cruzi parasite. Cytotoxicity assays were also performed in RAW 264.7 and VERO cells. Compound 5 presented the highest trypanocidal activity of the series, with trypanocidal values higher than nifurtimox for the trypomastigote and epimastigote stages., but presenting cytotoxic effects in the mammalian cells. A SAR study suggested that methoxy substitution at positions 2 and 5 in the designed scaffold seemed to be a key feature for the trypanocidal activity. Therefore, the coumarin-chalcone scaffold can be taken into account for further lead optimization and design new and more effective trypanocidal compounds.
RESUMO
This article describes the preparation and characterization of a selected series of coumarin derivatives with the aim of evaluating their antioxidant properties and their activity against Trypanosoma cruzi, the parasite responsible for Chagas disease. All the derivatives demonstrated moderate trypanocidal activity in the epimastigote and trypomastigote stages (clone Dm28c), with Compound 3 presenting the highest trypanocidal activity of the entire series, displaying higher activity than nifurtimox, which was used as a reference compound. In addition to the trypanocidal activity, this compound proved to have a very interesting antioxidant profile, as well as no cytotoxicity. These preliminary findings encouraged the authors to study the future structural optimization of this scaffold.