Glutathione peroxidase-like functions of 1,2-diselenane-4,5-diol and its amphiphilic derivatives: Switchable catalytic cycles depending on peroxide substrates
| Autor: | Kenta Arai, Akiko Kanamori, Ikumi Nakajima, Manami Saito, Michio Iwaoka, Moeka Sasaki, Yuumi Sato |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell Survival
Clinical Biochemistry Pharmaceutical Science 01 natural sciences Biochemistry Peroxide Medicinal chemistry Antioxidants Catalysis Diselenide Lipid peroxidation Structure-Activity Relationship Surface-Active Agents chemistry.chemical_compound Drug Discovery Tumor Cells Cultured Humans Molecular Biology Alkyl chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure Lipid peroxide 010405 organic chemistry Glutathione peroxidase Organic Chemistry Stereoisomerism Hydrogen Peroxide Peroxides 0104 chemical sciences Oxidative Stress 010404 medicinal & biomolecular chemistry chemistry Catalytic cycle Enzyme model Molecular Medicine lipids (amino acids peptides and proteins) Oxidation-Reduction HeLa Cells |
| Zdroj: | Bioorganic & Medicinal Chemistry. 29:115866 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2020.115866 |
| Popis: | Amphiphilic derivatives of (±)-trans-1,2-diselenane-4,5-diol (DSTox) decorated with long alkyl chains or aromatic substituents via ester linkages were applied as glutathione peroxidase (GPx)-like catalysts. The reduction of H2O2 with the diselenide catalysts was accelerated through a GPx-like catalytic cycle, in which the diselenide (Se-Se) bond was reduced to the diselenolate form ([Se-,Se-]) by coexisting dithiothreitol, and the generated highly active [Se-,Se-] subsequently reduced H2O2 to H2O retrieving the original Se-Se form. In the lipid peroxidation of lecithin/cholesterol liposomes induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), on the other hand, the Se-Se form directly reduced lipid peroxide (LOOH) to the corresponding alcohol (LOH), inhibiting the radical chain reaction, to exert the antioxidative effect. Thus, the two GPx-like catalytic cycles can be switched depending on the peroxide substrates. Furthermore, hydrophilic compounds with no or short alkyl groups (C3) showed high antioxidative activities for the catalytic reduction of H2O2, while lipophilic compounds with long alkyl chains (C6-C14) or aromatic substituents were more effective antioxidants against lipid peroxidation. In addition, these compounds showed low cytotoxicity in cultured HeLa cells and exhibited sufficient anti-lipid peroxidative activities, suggesting their potentials as selenium-based antioxidative drugs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect