Abstract

To discover novel multifunctional agents for the treatment of Parkinson’s disease, a series of 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives was designed, synthesized and evaluated. The results revealed that representative compound 3h possessed potent and selective MAO-B inhibitory activity (IC₅₀ = 0.062 µM), and its inhibitory mode was competitive and reversible. Additionally, 3h also displayed excellent anti-oxidative effect (ORAC = 2.27 Trolox equivalent), significant metal chelating ability and appropriate BBB permeability. Moreover, 3h exhibited good neuroprotective effect and anti-neuroinflammtory ability. These results indicated that compound 3h was a promising candidate for further development against PD.

摘要

为了发现用于治疗帕金森病的新型多功能药物，设计、合成并评估了一系列 2-(4-(苄氧基)-5-(羟基)苯基) 苯并噻唑衍生物。结果表明，代表性化合物3h具有强效和选择性的 MAO-B 抑制活性（IC ₅₀  = 0.062 µM），其抑制模式具有竞争性和可逆性。此外，3h还显示出优异的抗氧化作用（ORAC = 2.27 Trolox 当量）、显着的金属螯合能力和适当的 BBB 渗透性。此外，3h表现出良好的神经保护作用和抗神经炎症能力。这些结果表明化合物3h是针对 PD 进一步发展的有前途的候选者。