A Novel Oxo-Palmatine Derivative 2q as Potent Reversal Agents Against Alzheimer's Disease

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL

Drug Development Research Pub Date : 2025-03-13 DOI:10.1002/ddr.70073

Shuo Pang, Zhuo Li, Ao Liu, Zhuo-Hui Luo, Heqing Yin, Songqiao Fan, Junjie Shi, Ning Liu, Shuo Pan, Ya-Jun Yang, Guo-jun Zhang, Jun Chen

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引用次数: 0

Abstract

Palmatine (PAL), as an active ingredient in traditional Chinese medicine, had been demonstrated efficacy in ameliorating the manifestations of AD. Our research group has previously designed and synthesized the novel oxo-PAL derivative 2q and found that it has exhibited notable neuroprotective properties. However, compound 2q therapeutic impact on AD remains uncertain. In the current investigation, our findings demonstrated that compound 2q displayed significant anti-AβOs activity in vitro by using xCELLigence analysis, and showed a high likelihood of crossing the blood-brain barrier. Furthermore, administration of compound 2q yielded a notable amelioration in Aβ accumulation and hyperphosphorylation of Tau in 3×Tg mice. Additionally, it was observed that compound 2q potentially enhanced the pathological characteristics of AD by targeting Potassium/Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 (HCN2). In conclusion, compound 2q emerged as a promising candidate for AD treatment, as it effectively restored AD-associated pathological impairments. Furthermore, it has been identified as a potential target of HCN2, thereby offering novel avenues for the development of treatments for AD.

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来源期刊

Drug Development Research 医学-药学

CiteScore

6.40

自引率

2.60%

发文量

104

审稿时长

6-12 weeks

期刊介绍： Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.