title: New polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones: synthesis and ROS/RNS scavenging activities.
abstract: New polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones were prepared and assessed as reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavengers. The synthetic strategy involved the preparation of 2'-hydroxychalcones and 2'-hydroxycinnamylidenoacetophenones from base-catalyzed aldol reaction of appropriate 2'-hydroxyacetophenones and benzaldehydes/cinnamaldehydes, followed by an Algar-Flynn-Oyamada (AFO) reaction to give the polyalkoxy(flavon-3-ols and 3-hydroxy-2-styrylchromones). The last step of this synthetic route consisted in the cleavage of the protecting groups affording the expected polyhydroxylated derivatives. The present work consisted in the study of the in vitro scavenging activities of the synthetized compounds against the most physiologically relevant ROS [superoxide radical (O2(-)), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen ((1)O2) and peroxyl radical (ROO)] and RNS [nitric oxide (NO) and peroxynitrite anion (ONOO(-))]. Generally, all the tested new polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones exhibited scavenging effects dependent on the concentration, and with IC50 values found within the micromolar range. This work allowed the establishment of new structure-activity relationships and brought the knowledge about the selective choice of a structure depending on the targeted reactive species.
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Joana L C
authors.initials: JL
authors.lastname: Sousa
authors.affiliation: UCIBIO-REQUIMTE, Applied Chemistry Laboratory, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Carina
authors.initials: C
authors.lastname: Proença
authors.affiliation: UCIBIO-REQUIMTE, Applied Chemistry Laboratory, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Marisa
authors.initials: M
authors.lastname: Freitas
authors.affiliation: UCIBIO-REQUIMTE, Applied Chemistry Laboratory, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
authors.affiliation: QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address: artur.silva@ua.pt.
authors.forename: Artur M S
authors.initials: AM
authors.lastname: Silva
mesh_terms: D060326:Chemistry Techniques, Synthetic; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry*; D026361:Reactive Nitrogen Species / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry*
chemical_list: C000607213:2-styrylchromone; D002867:Chromones; D016166:Free Radical Scavengers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
keywords: 3-Hydroxy-2-styrylchromones; Antioxidant activity; Flavon-3-ols; Radical scavenging activity; Reactive nitrogen species; Reactive oxygen species