化学
丁酰胆碱酯酶
乙酰胆碱酯酶
阿切
胆碱酯酶
神经炎症
IC50型
药理学
促炎细胞因子
对接(动物)
抑制性突触后电位
酶
立体化学
生物化学
体外
炎症
内科学
医学
护理部
作者
Ling Lv,Mireguli Maimaitiming,Yan Huang,Jichen Yang,Shuxia Chen,Yanfeng Sun,Xuetao Zhang,Xin Li,Changhu Xue,Pingyuan Wang,Chang‐Yun Wang,Zhiqing Liu
标识
DOI:10.1016/j.ejmech.2023.115346
摘要
A series of quinazolin-4(3H)-one derivatives was designed through scaffold-hopping strategy and synthesized as novel multifunctional anti-AD agents demonstrating both cholinesterase inhibition and anti-inflammatory activities. Their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were evaluated, and the enzyme kinetics study as well as detailed binding mode via molecular docking were performed for selected compounds. MR2938 (B12) displayed promising AChE inhibitory activity with an IC50 value of 5.04 μM and suppressed NO production obviously (IC50 = 3.29 μM). Besides, it was able to decrease the mRNA levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6 and CCL2 at 1.25 μM. Further mechanism study suggested that MR2938 suppressed the neuroinflammation through blocking MAPK/JNK and NF-κB signaling pathways. All these results indicate that MR2938 is a good starting point to develop multifunctional anti-AD lead compounds.
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