Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France.
Aix Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Equipe Sondes Moléculaires en Biologie et Stress Oxydant (SMBSO), Service 522, 13397, Marseille, Cedex 20, France; Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Institute of Materials and Environmental Chemistry, Budapest University of Technology and Economics, Hungary.
Eur J Med Chem. 2016 Aug 25;119:197-217. doi: 10.1016/j.ejmech.2016.04.067. Epub 2016 Apr 29.
A series of new hybrid 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine oxide derivatives with different aromatic substitution (PPNs) were synthesized. These molecules were evaluated for their EPR spin trapping potential on eleven different radicals and NO-donation properties in vitro, cytotoxicity and vasoprotective effect on precontracted rat aortic rings. A subfamily of the new PPNs featured an antioxidant moiety occurring in natural phenolic acids. From the experimental screening of these hydroxyphenyl- and methoxyphenyl-substituted PPNs, biocompatible nitrones 4d, and 4g-4i deriving from caffeic, gallic, ferulic and sinapic acids, which combined improved EPR probing of ROS formation, vasorelaxant action and antioxidant potency, might be potential drug candidate alternatives to PBN and its analogues.
一系列具有不同芳香取代基的新型 2-(二乙氧基膦酰基)-N-(亚苄基)丙-2-胺氧化物衍生物（PPNs）被合成。这些分子在十一种不同的自由基上评估了它们的 EPR 自旋捕获潜力以及体外的 NO 供体性质、细胞毒性和对预先收缩的大鼠主动脉环的血管保护作用。新的 PPN 中的一个亚家族具有在天然酚酸中存在的抗氧化部分。从这些羟基苯基和甲氧基苯基取代的 PPN 的实验筛选中，可以得到生物相容性的硝酮 4d 和 4g-4i，它们分别来源于咖啡酸、没食子酸、阿魏酸和芥子酸，它们结合了改善的 ROS 形成的 EPR 探测、血管舒张作用和抗氧化能力，可能是 PBN 及其类似物的潜在药物候选替代物。
