A series of 6-substituted azaanthraquinone derivatives have been designed, synthesized, and their anti-inflammatory activities, antiaggregation effects on β-amyloid proteins, anticholinesterase and neuroprotective activity were tested. The new derivatives strongly suppressed NO and iNOS production and modulate the production of cytokines by decreasing TNF-a, IL-1β and IL-6 formation in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Meanwhile, the derivatives exhibited a significant in vitro inhibitory activity toward the self-induced Aβ aggregation. While, treatment of SH-SY5Y cells overexpressing the Swedish mutant form of human b-amyloid precursor protein (APPsw) with derivatives was associated with significant reduction of Aβ42 secretion levels. Moreover, the derivatives exhibited moderate inhibitory potency toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Further investigations indicated that compound 7b could attenuate H₂O₂-induced neurotoxicity toward SH-SY5Y neuroblastoma cells and half of the synthetic compounds were predicted to be able to cross the blood–brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. Taken together, azaanthraquinone derivatives targeting multiple pathogenetic factors deserves further investigation for prevention and treatment of AD.

设计，合成了一系列6-取代的氮杂蒽醌衍生物，并测试了它们的抗炎活性，对β-淀粉样蛋白的抗聚集作用，抗胆碱酯酶和神经保护活性。新的衍生物通过降低脂多糖（LPS）激活的RAW 264.7巨噬细胞中的TNF-α，IL-1β和IL-6形成，强烈抑制NO和iNOS的产生并调节细胞因子的产生。同时，这些衍生物对自诱导的Aβ聚集表现出显着的体外抑制活性。同时，用衍生物处理过表达人β-淀粉样蛋白前体蛋白（APPsw）瑞典突变型的SH-SY5Y细胞与Aβ42分泌水平的显着降低有关。而且，衍生物表现出对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的中等抑制力。进一步的调查表明，该化合物7b可能减弱H ₂ O ₂诱导的对SH-SY5Y神经母细胞瘤细胞的神经毒性，据预测，一半的合成化合物能够穿过血脑屏障（BBB）到达其在中枢神经系统（CNS）中的靶标。用于BBB的平行人工膜渗透测定。综上所述，针对多种致病因素的氮杂蒽醌衍生物值得进一步研究，以预防和治疗AD。