title: Synthesis and biological evaluation of new nitrogen-containing diselenides.
abstract: The antioxidant properties of organoselenium compounds have been extensively investigated with the aim of developing new drugs, since oxidative stress is responsible for a variety of chronic human diseases. Herein, we reported the synthesis of new nitrogen-containing diselenides by a simple and efficient synthetic route. The products were obtained in good to excellent yields and their identification and characterization were achieved by NMR and HRMS techniques. The new derivatives may represent promising structures with different biological activities, which can act against oxidative stress through diverse mechanisms of action. The glutathione peroxidase-like assay (GPx-like activity) of the new synthesized compounds indicated that they reduced H2O2 to water at the expense of PhSH. The best results were obtained with diselenide 2b, which was 9 times more active than the standard organoselenium drug ebselen and, in contrast, this compound was not reduced by hepatic TrxR. All of the new compounds inhibited Fe(II)-induced TBARS.
authors.affiliation: Laboratório de Síntese de Substâncias de Selênio Bioativas, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nascimento
authors.affiliation: Laboratório de Síntese de Substâncias de Selênio Bioativas, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Natasha L
authors.initials: NL
authors.lastname: Ferreira
authors.affiliation: Laboratório de Síntese de Substâncias de Selênio Bioativas, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Rômulo F S
authors.initials: RF
authors.lastname: Canto
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Schott
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Waczuk
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Perugia, Via del Liceo 1, 06134 Perugia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Sancineto
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Perugia, Via del Liceo 1, 06134 Perugia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Santi
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
authors.affiliation: Laboratório de Síntese de Substâncias de Selênio Bioativas, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil. Electronic address: albraga1@gmail.com.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Braga
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D054833:Isoindoles; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C042986:ebselen; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D054481:Thioredoxin Reductase 1; C516126:Txnrd1 protein, rat; D009584:Nitrogen
keywords: Amphetamine; Antioxidant; Diselenides; Ebselen; Glutathione peroxidase; Selenium