School of Pharmacy, North Sichuan Medical College, Nanchong, 637000, China.
School of Pharmacy, North Sichuan Medical College, Nanchong, 637000, China.
Eur J Med Chem. 2023 Mar 5;249:115142. doi: 10.1016/j.ejmech.2023.115142. Epub 2023 Jan 21.
To discover novel multifunctional agents for the treatment of Parkinson's disease, a series of 2-hydroxyl-4-benzyloxybenzyl aniline derivatives was designed, synthesized and evaluated. The biological screening indicated that representative compound 6h possessed excellent MAO-B inhibition (IC = 0.014 μM), high antioxidant activity (ORAC = 2.14 Trolox equivalent), good metal chelating ability, appropriate BBB permeability and significant neuroprotective effect. Additionally, 6h exhibited great ability to alleviate the neuroinflammtion by suppressing the activation of NF-κB pathway in vitro. Furthermore, 6h can also ameliorate MPTP induced Parkinson's disease symptoms in mice by improving the dopamine level and repressing oxidative damage. These results indicated that compound 6h was a promising candidate for further development against PD.
为了发现治疗帕金森病的新型多功能药物，设计、合成并评价了一系列 2-羟基-4-苄氧基苯甲胺衍生物。生物筛选结果表明，代表性化合物 6h 对 MAO-B 具有优异的抑制作用（IC = 0.014 μM）、高抗氧化活性（ORAC = 2.14 Trolox 当量）、良好的金属螯合能力、适当的 BBB 渗透性和显著的神经保护作用。此外，6h 通过抑制 NF-κB 通路的激活，在体外具有很好的抑制神经炎症的能力。此外，6h 还可以通过提高多巴胺水平和抑制氧化损伤来改善 MPTP 诱导的小鼠帕金森病症状。这些结果表明，化合物 6h 是进一步开发 PD 治疗药物的有前途的候选药物。
