Design, synthesis, and biological evaluation of histone deacetylase inhibitors possessing glutathione peroxidase-like and antioxidant activities against Alzheimer's disease

被引：21
|
作者：
Hu, Jinhui [1 ]
An, Baijiao [1 ]
Pan, Tingting [1 ]
Li, Zhengcunxiao [1 ]
Huang, Ling [1 ]
Li, Xingshu [1 ]
机构：
[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2018年 / 26卷 / 21期
基金：
中国国家自然科学基金;
关键词：
Alzheimer's disease; Histone deacetylase inhibitors; Glutathione peroxidase-like activity; Antioxidant activities; Multi-target-directed ligands; TARGET-DIRECTED LIGANDS; NEURODEGENERATIVE DISEASES; MOUSE MODEL; HDAC6; ACETYLATION; DERIVATIVES; SELENIUM; TAU; AGGREGATION; FLUORESCEIN;
D O I：
10.1016/j.bmc.2018.10.022
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A series of hybrids containing the pharmacophores of the histone deacetylase (HDAC) inhibitor, SAHA, and the antioxidant ebselen were designed and synthesized as multi-target-directed ligands against Alzheimer's disease. An in vitro assay indicated that some of these molecules exhibit potent HDAC inhibitory activity and ebselen-related pharmacological effects. Specifically, the optimal compound 7f was found to be a potent HDAC inhibitor (IC50 = 0.037 mu M), possessing rapid hydrogen peroxide scavenging activity and glutathione peroxidase-like activity (nu(0) = 150.0 mu M min(-1)) and good free oxygen radical absorbance capacity (value of ORAC: 2.2). Furthermore, compound 7f showed significant protective effects against damage induced by H2O2 and the ability to prevent ROS accumulation in PC12 cells.
引用
收藏
页码：5718 / 5729
页数：12
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