title: Uncovering novel 3-hydroxy-4-pyridinone metal ion complexes with potential anti-inflammatory properties.
abstract: Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) type, with one (Hmpp) or two methyl groups (Hdmpp), have been reported to possess biomedical, chemical and analytical applications. In this first screening study aiming to uncover new promising agents to mitigate the oxidative damage highly present in several metabolic disorders, such as diabetes mellitus, we assessed the potential of twelve 3,4-HPO metal ion complexes to modulate oxidative burst in human neutrophils. Metal ion 3,4-HPO complexes of Ni, Fe, V, Co, Cu and Zn were synthesized and tested up to 15μM. Among all the compounds, [Cu(mpp)2] and [Cu(dmpp)2] exhibited the highest scavenging capacity against superoxide radical (O2(-)) (IC50=0.36±0.07 and 0.30±0.06μM, respectively) and against hypochlorous acid (HOCl) (IC50=0.6±0.3 and 0.4±0.1μM, respectively). In the particular case of O2(-), [Fe(mpp)3] and [Fe(dmpp)3] (both at 15μM) presented 35% and 22% of inhibition, respectively, while all the other compounds were neither able to scavenge O2(-) nor stimulate its production. Regarding the scavenging capacity against hydrogen peroxide (H2O2), all the compounds showed low efficiency (from 6-39%). Finally, with exception of [VO(mpp)2] and [VO(dmpp)2], all compounds exhibited scavenging activity against HOCl (39-81%) and the most efficient compounds were Cu(II) and Zn(II) complexes. Thus, these preliminary results uncover promising new metal ion complexes, inhibitors of neutrophil's oxidative burst, with potential anti-inflammatory properties, which may be seen as an useful strategy for further studies in the treatment of a number of diseases where oxidative damage is a serious issue.
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal. Electronic address: rcchiste@ff.up.pt.
authors.forename: Renan Campos
authors.initials: RC
authors.lastname: Chisté
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ribeiro
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal.
authors.forename: Marisa
authors.initials: M
authors.lastname: Freitas
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 404169-007 Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Leite
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 404169-007 Porto, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Moniz
authors.affiliation: UCIBIO, REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Rangel
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal. Electronic address: egracas@ff.up.pt.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D008670:Metals / Q000737:chemistry*; D009504:Neutrophils / Q000187:drug effects; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D008670:Metals; D011728:Pyridones; C020366:3-hydroxy-4-pyridone
keywords: Human neutrophils; Hydrogen peroxide; Hypochlorous acid; Inflammation; Oxidative burst; Superoxide radical