Because of the complex etiology in neuroinflammatory process, the design of multifunctional agents is a potent strategy to cure neuroinflammatory diseases including AD and PD. Herein, based on the combination principles, 23 of N-salicyloyl tryptamine derivatives as multifunctional agents were designed and their new application for anti-neuroinflammation was disclosed. In cyclooxygenase assay, two compounds 3 and 16 displayed extremely preferable COX-2 inhibition than N-salicyloyl tryptamine. In LPS-induced C6 and BV2 cell models, some compounds decreased the production of proinflammatory mediators NO, PGE₂, TNF-α, iNOS, COX-2 and ROS, while increased the production of IL-10. Among them, compound 3 and 16 showed approximately six-fold better inhibition on nitric oxide production than N-salicyloyl tryptamine in C6. Besides, compounds 3, 13 and 16 attenuated the activation of BV2 and C6 cells. More importantly, in vivo, compounds 3 and 16 reduced GFAP and Iba-1 levels in the hippocampus, and displayed neuroprotection in Nissl staining. Besides, both compounds 3 and 16 had high safety (LD₅₀ > 1000 mg/kg). Longer plasma half-life of compounds 3 and 16 than melatonin supported combination strategy. All these results demonstrated that N-salicyloyl tryptamine derivatives are potential anti-neuroinflammation agents for the treatment of neurodegenerative disorder.

由于神经炎性过程的病因复杂，因此设计多功能药物是治疗包括AD和PD在内的神经炎性疾病的有效策略。在此，基于组合原理，设计了23种N-水杨酰类色胺衍生物作为多功能剂，并公开了其在抗神经炎症中的新应用。在环氧合酶测定中，两种化合物3和16表现出比N-水杨酰类色胺更高的COX-2抑制性。在LPS诱导的C6和BV2细胞模型中，某些化合物降低了促炎性介质NO，PGE ₂，TNF-α，iNOS，COX-2和ROS的产生，同时增加了IL-10的产生。其中，化合物3和16结果表明，在C6中，一氧化氮的抑制作用比N-水杨酰色胺高约6倍。此外，化合物3，13和16衰减BV2和C6细胞的活化。更重要的是，在体内，化合物3和16降低海马中的GFAP和Iba-1水平，并在Nissl染色中显示出神经保护作用。此外，化合物3和16均具有较高的安全性（LD ₅₀  > 1000 mg / kg）。化合物3和16的血浆半衰期更长比褪黑激素支持的联合策略。所有这些结果表明，N-水杨酰类色胺衍生物是用于治疗神经退行性疾病的潜在抗神经炎症剂。