Saleta Vazquez-Rodriguez, Roberto F. Guíñez, Maria J. Matos, Claudio Olea-Azar, Juan D. Maya, Eugenio Uriarte and Lourdes Santana Pages 537 - 543 ( 7 )
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.
Chagas disease, Chalcone, Coumarin, Cytotoxicity, Natural products, Structure-activity relationship, Trypanosoma cruzi.
Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Campus Vida s/n, 15782, Santiago de Compostela, Spain.