title: Synthesis and antioxidant activity of O-alkyl selenocarbamates, selenoureas and selenohydantoins.
abstract: The preparation of three different families of lipophilic organoselenium compounds (aryl- and sugar-derived selenoureas, O-alkyl selenocarbamates and selenohydantoins) has been carried out in order to evaluate their in vitro antioxidant profile, analyzing the influence of the selenium-containing functional group, and the substituents on the activity. Title compounds have therefore been studied for the first time as free radical, hydrogen peroxide, alkyl peroxides and nitric oxide scavengers using colorimetric methods; furthermore, their glutathione peroxidase-like activity has also been analyzed by NMR spectroscopy. Free radical scavenging activity has been evaluated using the DPPH method; the strongest free radical scavengers were found to be both, aryl- and sugar-derived selenoureas, with EC₅₀ values ranging 19-46 μM. Concerning anti-H₂O₂ activity, measured by the horseradish peroxidase-mediated oxidation of phenol red, the best results were achieved for aryl selenohydantoins, showing a 61-76% inhibition at 0.5 mM concentration. Organoselenium compounds were also found to be capable of inhibiting the chain reaction involving lipid peroxidation (ferric thiocyanate method); thus, when tested at 0.74 mM, sugar selenocarbamates exhibited 49-71% inhibition of alkyl peroxides-mediated degradation of linoleic acid. Nitric oxide scavenging was studied by transforming sodium nitroprusside into nitrite ion, which in turn was transformed into an easily UV-detectable azocompound; aryl selenocarbamates exhibited 64-80% inhibition at 0.71 mM concentration. It has also been demonstrated that selenoxo compounds can behave as excellent glutathione peroxidase mimics; thus a 0.05 molar equiv. of the title compounds catalyzed efficiently the H₂O₂-mediated oxidation of dithiothreitol into the corresponding cyclic disulfide, mimicking removal of H₂O₂ exerted by glutathione peroxidase; t(1/2) values were found to be quite low for aryl- and sugar-derived selenoureas (2.0-12.7 min).
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
authors.forename: Penélope
authors.initials: P
authors.lastname: Merino-Montiel
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Maza
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martos
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain. Electronic address: osc-lopez@us.es.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: López
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Maya
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain. Electronic address: bolanos@us.es.
authors.forename: José G
authors.initials: JG
authors.lastname: Fernández-Bolaños
mesh_terms: D000478:Alkylation; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006827:Hydantoins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009994:Osmolar Concentration; D026361:Reactive Nitrogen Species / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002219:Carbamates; D016166:Free Radical Scavengers; D006827:Hydantoins; D016566:Organoselenium Compounds; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C081959:selenourea; D014508:Urea