当前位置: X-MOL 学术ACS Chem. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5)
ACS Chemical Neuroscience ( IF 5 ) Pub Date : 2018-04-04 00:00:00 , DOI: 10.1021/acschemneuro.8b00014
Wei Ni 1 , Huan Wang 2, 3 , Xiaokang Li 1 , Xinyu Zheng 1 , Manjiong Wang 1 , Jian Zhang 2, 4 , Qi Gong 2, 4 , Dazheng Ling 1 , Fei Mao 1 , Haiyan Zhang 2, 4 , Jian Li 1
Affiliation  

On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of Alzheimer’s disease (AD), and the lead compound 2 has proven this method was feasible in AD mouse models. In this study, our work focused on exploring alternative novel tadalafil derivatives (3as). Among the 19 analogues, compound 3c exhibited good selective dual-target AChE/PDE5 inhibition and good blood-brain barrier (BBB) permeability. Moreover, its citrate (3c·Cit) possessed improved water solubility and good effects against scopolamine-induced cognitive impairment with inhibition of cortical AChE activities and enhancement of cAMP response element-binding protein (CREB) phosphorylation ex vivo.

中文翻译:

新型他达拉非衍生物可通过抑制乙酰胆碱酯酶(AChE)和磷酸二酯酶5(PDE5)减轻小S碱诱导的小鼠认知障碍。

根据药物置换和再开发策略,最近已报道了第一代乙酰胆碱酯酶(AChE)和磷酸二酯酶5(PDE5)的双靶标抑制剂是治疗阿尔茨海默氏病(AD)的一种潜在的新颖治疗方法,前导化合物2证明了该方法在AD小鼠模型中是可行的。在这项研究中,我们的工作重点是探索替代的新型他达拉非衍生物(3as)。在19种类似物中,化合物3c表现出良好的选择性双靶AChE / PDE5抑制作用和良好的血脑屏障(BBB)渗透性。而且,它的柠檬酸盐(3c·Cit)具有改善的水溶性,并通过抑制皮层AChE活性和增强离体的cAMP反应元件结合蛋白(CREB)磷酸化而对东pol碱引起的认知障碍有良好的作用。
更新日期:2018-04-04
down
wechat
bug