Design, synthesis, and biological evaluation of novel 2-acetylphenol-rivastigmine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease

被引：6

作者：

Deng, Cong ^{[1
]}

Mi, Jing ^{[2
]}

Zhou, Yi ^{[2
]}

Li, Xinjuan ^{[2
]}

Liu, Zhengwei ^{[2
]}

Sang, Zhipei ^{[2
]}

Li, Hui ^{[3
]}

机构：

[1] Guangzhou Univ Chinese Med, Guangdong Prov Hosp Chinese Med, Affiliated Hosp 2, 111 Dade Rd, Guangzhou 510120, Peoples R China

[2] Nanyang Normal Univ, Coll Chem & Pharmaceut Engn, Nanyang 473061, Peoples R China

[3] Jinan Univ, Guangzhou Red Cross Hosp, Dept Tradit Chinese Med, Guangzhou 510220, Peoples R China

来源：

MEDICINAL CHEMISTRY RESEARCH | 2022年 / 31卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Alzheimer's disease; 2-Acetylphenol-rivastigmine hybrids; Multi-functional agents; Neuroprotective effect; Blood-brain barrier; penetration; TARGET-DIRECTED LIGANDS; CHOLINESTERASE-INHIBITORS; DERIVATIVES;

D O I：

10.1007/s00044-022-02899-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein, a series of 2-acetylphenol-rivastigmine hybrids were rationally designed as multifunctional agents for the treatment of AD through multi-target-directed ligands (MTDLs) strategy. The biological activity in vitro showed that compound 3c was a pseudo-irreversible and selective huAChE inhibitor (IC50 = 8.7 mu M). Compound 3c was also a significant antioxidant with ORAC value of 1.2 eq. Moreover, compound 3c showed potent MAO-B inhibitory activity with IC50 values of 2.9 mu M. In addition, compound 3c displayed selective metal chelation property. Furthermore, compound 3c showed significant neuroprotective effect on H2O2-induced PC12 cells injury. More importantly, compound 3c displayed favorable drug-like property and good blood brain barrier permeability in vitro. Thus, compound 3c was a promising multifunctional agent in vitro for the treatment of AD, deserving for further investigations. [GRAPHICS] .

引用

页码：1035 / 1048

页数：14

共 30 条

[1]

Alzheimers Association, 2015, Alzheimers Dement, V11, P332

[2]

[Anonymous], 2019, WORLD ALZHEIMER REPO, P1

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