title: Synthesis, antioxidant and antichagasic properties of a selected series of hydroxy-3-arylcoumarins.
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 hydroxy-3-arylcoumarins are described, exerting both antioxidant and trypanocidal activity. Among the compounds synthesized, compound 8 showed the most interesting profile, presenting a moderate scavenging ability for peroxyl radicals (ORAC-FL=2.23) and a high degree of selectivity towards epimastigotes stage of the parasite T. cruzi (IC50=1.31μM), higher than Nifurtimox (drug currently used for treatment of Chagas disease). Interestingly, the current study revealed that small structural changes in the hydroxy-3-arylcoumarin core allow modulating both activities, suggesting that this scaffold has desirable properties for the development of promising classes of antichagasic compounds.
authors.affiliation: Free Radical and Antioxidants Laboratory, Inorganic and Analytical Department, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile.
authors.forename: Natalia
authors.initials: N
authors.lastname: Robledo-O'Ryan
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: mariacmatos@gmail.com.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Saleta
authors.initials: S
authors.lastname: Vazquez-Rodriguez
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.affiliation: Free Radical and Antioxidants Laboratory, Inorganic and Analytical Department, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile; Department of Environmental Sciences, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Moncada-Basualto
authors.affiliation: Free Radical and Antioxidants Laboratory, Inorganic and Analytical Department, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Mura
authors.affiliation: Department of Molecular Pharmacology and Clinical, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Michel
authors.initials: M
authors.lastname: Lapier
authors.affiliation: Department of Molecular Pharmacology and Clinical, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.affiliation: Free Radical and Antioxidants Laboratory, Inorganic and Analytical Department, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Sergio Livingstone Polhammer 1007, Independencia, Santiago, Chile. Electronic address: colea@uchile.cl.
authors.forename: Claudio
authors.initials: C
authors.lastname: Olea-Azar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D002522:Chlorocebus aethiops; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D000067996:RAW 264.7 Cells; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D000975:Antioxidants; D003374:Coumarins; D014344:Trypanocidal Agents
keywords: Antioxidant activity; Chagas disease; Hydroxy-3-arylcoumarins; Trypanosome