1. Design, synthesis, and biological evaluation of novel 4-oxobenzo[d]1,2,3-triazin-benzylpyridinum derivatives as potent anti-Alzheimer agents.
- Author
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Hosseini F, Ramazani A, Mohammadi-Khanaposhtani M, Barazandeh Tehrani M, Nadri H, Larijani B, and Mahdavi M
- Subjects
- Humans, Neuroprotective Agents pharmacology, Pyridines chemistry, Alzheimer Disease drug therapy, Neuroprotective Agents therapeutic use, Pyridines chemical synthesis
- Abstract
Novel 4-oxobenzo[d]1,2,3-triazin derivatives bearing pyridinium moiety 6a-q were synthesized and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Most of the synthesized compounds showed good inhibitory activity against AChE. Among the synthesized compounds, the compound 6j exhibited the highest AChE inhibitory activity. It should be noted that these compounds displayed low anti-BuChE activity with the exception of the compound 6i, as it exhibited BuChE inhibitory activity more than donepezil. The kinetic study of the compound 6j revealed that this compound inhibited AChE in a mixed-type inhibition mode. This finding was also confirmed by the docking study. The latter study demonstrated that the compound 6j interacted with both the catalytic site and peripheral anionic site of the AChE active site. The compound 6j was also observed to have significant neuroprotective activity against H
2 O2 -induced PC12 oxidative stress, but low activity against β-secretase., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
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