Synthesis and biological evaluation of a new series of ebselen derivatives as glutathione peroxidase (GPx) mimics and cholinesterase inhibitors against Alzheimer's disease.
A series of ebselen derivatives were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and glutathione peroxidase (GPx) mimics. Most of the compounds were found to be potent against AChEs and BuChE, compounds 5e and 5i, proved to be the most potent against AChE with IC₅₀ values of 0.76 and 0.46 μM, respectively. Among these hybrids, most of the compounds were found to be good GPx mimics compare with ebselen. The selected compounds 5e and 5i were also used to determine the catalytic parameters and in vitro hydrogen peroxide scavenging activity. The results indicate that compounds 5e and 5i may be excellent multifunctional agents for the treatment of AD.
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Zonghua
Z
Luo
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China.
Liang
L
Liang
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Jianfei
J
Sheng
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Yanqing
Y
Pang
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Jianheng
J
Li
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Ling
L
Huang
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: xsli219@yahoo.com.
Xingshu
X
Li
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D000975:Antioxidants / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D001393:Azoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D005979:Glutathione Peroxidase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D054833:Isoindoles; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding
C000591910:5,6-dimethoxy-2-(4-(2-(piperidin-1-yl)ethoxy)phenyl)benzo(d)(1,2)selenazol-3(2H)-one; C000591909:5,6-dimethoxy-2-(4-(piperidin-1-ylmethyl)phenyl)benzo(d)(1,2)selenazol-3(2H)-one; D000975:Antioxidants; D001393:Azoles; D001672:Biocompatible Materials; D002800:Cholinesterase Inhibitors; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D005979:Glutathione Peroxidase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
Alzheimer’s disease; Cholinesterase inhibitors; GPx mimics