Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 125, Issue -, Pages 288-298Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.09.037
Keywords
Alzheimer's disease; Azepino[4,3-b]indole; Butyrylcholinesterase; N-Methyl D-aspartate receptor; Neuroprotection
Categories
Funding
- MIUR, Italy [PRIN 2009ESXPT2_005]
Ask authors/readers for more resources
Several 6-substituted 3,4,5,6-tetrahydroazepino[4,3-b]indol-1(2H)-one (THAI) derivatives were synthesized and evaluated for their activity as cholinesterase (ChE) inhibitors. The most potent inhibitors were identified among 6-(2-phenylethyl)-THAI derivatives, and in particular compounds 12b and 12d proved to be very active against human BChE (IC50 = 13 and 1.8 nM, respectively), with 1000-fold selectivity over AChE. Structure-activity relationships highlighted critical features (e.g., ring fusion [4,3-b], integrity of the lactam CONH function) and favorable physicochemical properties of the 6-(2-phenylethyl) group (i.e., optimal position, size and lipophilicity of phenyl substituents). The effects of a number of compounds against NMDA-induced SH-SY5Y neuronal cell injury were also evaluated. Treatment with 12b increased cell viability in SH-SY5Y cells pretreated with 250 mu M NMDA, with significant effects (P < 0.05) at concentrations between 0.5 and 5 mu M. These findings suggest that THAI can be used as a scaffold for developing new drug leads for the treatment of Alzheimer-type neurodegeneration syndrome. (C) 2016 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available