title: Pretreatment with natural flavones and neuronal cell survival after oxidative stress: a structure-activity relationship study.
abstract: Quercetin shows structural features that have been related to the antioxidant potency of flavonoids and also shows neuroprotection in different models of oxidative death. Because only a few studies have focused on the flavonoid structural requirements for neuroprotection, this work evaluated the protective capacity of 13 flavones structurally related to quercetin, isolated from Kenyan plants, to rescue primary cerebellar granule neurons from death induced by a treatment with 24 h of hydrogen peroxide (150 microM). Each flavone (0-100 microM) was applied 24 h prior to the oxidative insult, and neuronal viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results suggest that the o-dihydroxy substitution in the B-ring is not necessary to afford neuroprotection and could be partly responsible for neurotoxic effects. Furthermore, the hydroxy substitutions in the positions C3 (C-ring) in C5 and C7 (A-ring) would be important for neuroprotection in this model.
authors.affiliation: Departmento de Neuroquimica, Instituto de Investigaciones Biologicas Clemente Estable, Montevideo, Uruguay. echever@iibce.edu.uy
authors.forename: Carolina
authors.initials: C
authors.lastname: Echeverry
authors.forename: Florencia
authors.initials: F
authors.lastname: Arredondo
authors.forename: Juan Andres
authors.initials: JA
authors.lastname: Abin-Carriquiry
authors.forename: Jacob Ogweno
authors.initials: JO
authors.lastname: Midiwo
authors.forename: Charles
authors.initials: C
authors.lastname: Ochieng
authors.forename: Leonidah
authors.initials: L
authors.lastname: Kerubo
authors.forename: Federico
authors.initials: F
authors.lastname: Dajas
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology*; D007630:Kenya; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010944:Plants / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D047309:Flavones; D018696:Neuroprotective Agents