Design, synthesis, and biological evaluation of novel 2-acetylphenol-rivastigmine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease
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] .
基金：
National Natural Science Foundation of China [81774239]; Special Project of Nanyang Normal University [2020ZX015, 2020QN036]
第一作者机构：[1]Guangzhou Univ Chinese Med, Guangdong Prov Hosp Chinese Med, Affiliated Hosp 2, 111 Dade Rd, Guangzhou 510120, Peoples R China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Deng Cong,Mi Jing,Zhou Yi,et al.Design, synthesis, and biological evaluation of novel 2-acetylphenol-rivastigmine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease[J].MEDICINAL CHEMISTRY RESEARCH.2022,31(6):1035-1048.doi:10.1007/s00044-022-02899-7.
APA：
Deng, Cong,Mi, Jing,Zhou, Yi,Li, Xinjuan,Liu, Zhengwei...&Li, Hui.(2022).Design, synthesis, and biological evaluation of novel 2-acetylphenol-rivastigmine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.MEDICINAL CHEMISTRY RESEARCH,31,(6)
MLA：
Deng, Cong,et al."Design, synthesis, and biological evaluation of novel 2-acetylphenol-rivastigmine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease".MEDICINAL CHEMISTRY RESEARCH 31..6(2022):1035-1048
