Merino-Montiel Penélope, Maza Susana, Martos Sergio, López Óscar, Maya Inés, Fernández-Bolaños José G
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Apartado 1203, E-41071 Seville, Spain.
Eur J Pharm Sci. 2013 Feb 14;48(3):582-92. doi: 10.1016/j.ejps.2012.12.016. Epub 2012 Dec 31.
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).
为了评估三种不同系列的亲脂性有机硒化合物（芳基和糖衍生的硒脲、O-烷基硒代氨基甲酸盐和硒乙内酰脲）的体外抗氧化特性，分析含硒官能团和取代基对活性的影响，我们进行了这些化合物的制备。因此，首次使用比色法研究了标题化合物作为自由基、过氧化氢、烷基过氧化物和一氧化氮清除剂的性能；此外，还通过核磁共振光谱分析了它们的谷胱甘肽过氧化物酶样活性。使用DPPH法评估了自由基清除活性；发现最强的自由基清除剂是芳基和糖衍生的硒脲，其EC₅₀值范围为19 - 46 μM。关于通过辣根过氧化物酶介导的酚红氧化来测量的抗H₂O₂活性，芳基硒乙内酰脲取得了最佳结果，在0.5 mM浓度下显示出61 - 76%的抑制率。还发现有机硒化合物能够抑制涉及脂质过氧化的链反应（硫氰酸铁法）；因此，当在0.74 mM下测试时，糖硒代氨基甲酸盐对烷基过氧化物介导的亚油酸降解表现出49 - 71%的抑制率。通过将硝普钠转化为亚硝酸根离子来研究一氧化氮清除，亚硝酸根离子又转化为易于紫外检测的偶氮化合物；芳基硒代氨基甲酸盐在0.71 mM浓度下表现出64 - 80%的抑制率。还证明了硒氧代化合物可以表现为出色的谷胱甘肽过氧化物酶模拟物；因此，0.05摩尔当量的标题化合物有效地催化了H₂O₂介导的二硫苏糖醇氧化为相应的环状二硫化物，模拟了谷胱甘肽过氧化物酶对H₂O₂的清除作用；发现芳基和糖衍生的硒脲的t(1/2)值相当低（2.0 - 12.7分钟）。
