Synthesis and biological evaluation of new nitrogen-containing diselenides

• Published in: European journal of medicinal chemistry Vol. 87; pp. 131 - 139
• Main Authors: Nascimento, Vanessa, Ferreira, Natasha L., Canto, Rômulo F.S., Schott, Karen L., Waczuk, Emily P., Sancineto, Luca, Santi, Claudio, Rocha, João B.T., Braga, Antonio L.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 24-11-2014
• Subjects: Amphetamine; Antioxidant; Antioxidants - chemical synthesis; Antioxidants - pharmacology; Azoles - pharmacology; Brain - drug effects; Diselenides; Ebselen; Glutathione peroxidase; Glutathione Peroxidase - metabolism; Humans; Hydrogen Peroxide - metabolism; Lipid Peroxidation - drug effects; Liver - enzymology; Magnetic Resonance Spectroscopy; Molecular Structure; Nitrogen - chemistry; Organoselenium Compounds - chemical synthesis; Organoselenium Compounds - pharmacology; Oxidation-Reduction; Oxidative Stress - drug effects; Reactive Oxygen Species - metabolism; Selenium; Thiobarbituric Acid Reactive Substances - chemistry; Thiobarbituric Acid Reactive Substances - metabolism; Thioredoxin Reductase 1 - metabolism; NADPH; SAR; EDC; (PhSe)2; Gln; CDI; MDA; LDH; Trp; ALA-D; Selenium; GSH; TrxR; Glutathione peroxidase; UV; DCC; HMRS; Diselenides; Ebselen; TBARS; Antioxidant; GPx; m.p; T50; Sec; NMR; Amphetamine; ROS; S1
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.09.022

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.
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•New Nitrogen-containing diselenides were synthesized.•The compounds were evaluated “in vitro” for their antioxidant activity.•These novel diselenides show better GPx-like activity than the standards.•All of the new compounds inhibited Fe(II)-induced TBARS.•Some compounds were good substrates for TrxR.