title: Synthesis of chlorinated flavonoids with anti-inflammatory and pro-apoptotic activities in human neutrophils.
abstract: Neutrophils are considered the central cells of acute inflammation. Flavonoids have been suggested as therapeutic agents to avoid damages induced by inflammatory processes. It is well known the reactivity of flavonoids with hypochlorous acid produced by neutrophils, to form stable mono and dichlorinated products. In this study, we synthesized novel chlorinated flavonoids and investigated their effect in neutrophils' oxidative burst and in its lifespan, in comparison with the parent non-chlorinated flavonoids. The obtained results demonstrate that chlorinated flavonoids were more efficient than their parent compounds in modulating neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils. Some of the tested flavonoids drive neutrophil apoptosis in a caspase 3-dependent fashion. The present data showed that 8-chloro-3',4',5,7-tetrahydroxyflavone (4a) constitute an alternative anti-inflammatory therapy, due to the proven ability to suppress mechanisms engaged at the onset and progression of inflammation.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal. Electronic address: marisafreitas@ff.up.pt.
authors.forename: Marisa
authors.initials: M
authors.lastname: Freitas
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ribeiro
authors.affiliation: Departamento de Química & QOPNA, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tomé
authors.affiliation: Departamento de Química & QOPNA, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Artur M S
authors.initials: AM
authors.lastname: Silva
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal. Electronic address: egracas@ff.up.pt.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D006843:Hydrocarbons, Chlorinated
keywords: Apoptosis; Caspase 3; Flavonoids; Neutrophils; Reactive species