Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de República, Iguá 4225, 11400 Montevideo, Uruguay.
Eur J Med Chem. 2012 Dec;58:44-9. doi: 10.1016/j.ejmech.2012.09.044. Epub 2012 Oct 5.
Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD). Hydroxyphenyl nitrones, derivatives of the nitrone spin trap alpha-phenyl-N-tert-butylnitrone (PBN), were synthesized and their antioxidant, anti-inflammatory and neuroprotective activity in neural cells evaluated. These hydroxyphenyl nitrones 5-7 were synthesized by reaction of the corresponding hydroxybenzaldehyde with N-tert-butyl hydroxylamine under microwave irradiation. They showed good peroxyl free radical scavenger capacities, analyzed by oxygen radical absorbance capacity (ORAC). Also inhibited peroxynitrite-mediated tyrosine nitration of alpha-synuclein in vitro and protected human neuroblastoma (SH-SY5Y) cells against SIN-1 and 6-OHDA toxicity when micromolar concentrations were used. Besides, the hydroxyphenyl nitrones evaluated showed anti-inflammatory activity modulating nitrite production in primary neural cell cultures of astrocytes and microglia treated with lipopolysaccharide (LPS), a potent inflammatory agent. These experimental data suggest a potential therapeutic use of these hydroxyphenyl nitrones against oxygen and nitrogen reactive species involved in neurodegenerative pathology.
氧化应激在神经退行性疾病（如帕金森病）中神经元死亡中起着重要作用。羟基苯基硝酮，氮自由基捕获剂α-苯基-N-叔丁基硝酮（PBN）的衍生物，已被合成，并对其在神经细胞中的抗氧化、抗炎和神经保护活性进行了评价。这些羟基苯基硝酮 5-7 是通过在微波辐射下用相应的羟基苯甲醛与 N-叔丁基羟胺反应合成的。它们具有良好的过氧自由基清除能力，通过氧自由基吸收能力（ORAC）分析。此外，它们还能抑制过氧亚硝酸盐介导的α-突触核蛋白的酪氨酸硝化，当使用微摩尔浓度时，能保护人神经母细胞瘤（SH-SY5Y）细胞免受 SIN-1 和 6-OHDA 的毒性。此外，评估的羟基苯基硝酮还表现出抗炎活性，调节脂多糖（LPS）处理的星形胶质细胞和小胶质细胞原代神经细胞培养物中亚硝酸盐的产生，LPS 是一种有效的炎症介质。这些实验数据表明，这些羟基苯基硝酮可能具有治疗神经退行性病变中涉及的氧和氮反应性物质的潜在用途。
