Evaluation of Antioxidant and Antitrypanosomal Properties of a Selected Series of Synthetic 3‐Carboxamidocoumarins. Issue 15 (30th September 2016)

• Record Type: Journal Article
• Authors: Muñoz, Andrea; Fonseca, André; Matos, Maria J.; Uriarte, Eugenio; Santana, Lourdes; Borges, Fernanda; Figueroa, Roberto; Olea Azar, Claudio
• Is Part Of: ChemistrySelect. Volume 1:Issue 15(2016)
• Page Start: 4957
• Page End: 4964
• Publication Date: 2016-09-30
• Subjects: Antioxidant activity -- Carboxamidocoumarins -- Chagas disease -- Trypanosoma cruzi; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201601336
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: Oxidative stress is involved in several parasitic diseases such as Chagas. Agents able to selectively modulate biochemical processes involved in the disease represent promising multifunctional agents for the delay or abolishment of the progression of this pathology. In the current work, differently substituted 3‐carboxamidocoumarins exerting both antioxidant and trypanocidal activities are described. Among the compounds synthesized, compound3 ( N ‐(4‐hydroxyphenyl)coumarin‐3‐carboxamide) showed the most interesting antioxidant profile, presenting 53.2 % superoxide radical scavenging and the highest ORAC‐FL value (ORAC‐FL=1.87) of the series. In the trypanocidal study, compounds9 ( N ‐(quinolin‐6‐yl)coumarin‐3‐carboxamide) and10 ( N ‐(quinolin‐3‐yl)coumarin‐3‐carboxamide) presented high activity in epimastigote stage and low activity in trypomastigote stage, as well as low cytotoxic effects. Additionally, these compounds decreased mitochondrial transmembrane potential in epimastigote Dm28c. Based on these results, compounds9 and10 proved to be good candidates for further studies. Interestingly, the current study revealed that small structural changes in this scaffold allow modulating both activities, suggesting that these molecules present the desirable properties for the development of promising classes of antichagasic compounds. Abstract : 3‐Carboxamidocoumarins exerting antioxidant and trypanocidal activities were studied. Some compounds presented high ORAC‐FL, superoxide and hydroxyl radicals scavenging, as well as high antitrypanosomal activity, displaying low cytotoxic effects. Interestingly, the current study revealed that small structural changes allow modulating both activities, suggesting that these molecules present a promising profile for the development of antichagasic agents.