Abstract
Aim: Cholinesterase inhibitors and radical scavengers have been recognized as powerful symptomatic anti-Alzheimer's disease agents. Hence, the present study aimed to develop new triazineamides as potent anticholinesterase and antioxidant agents. Methods: Triazineamide (7a-i) derivatives were synthesized using cyanuric chloride via nucleophilic substitution followed by condensation. Ellman assay, 2,2-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging assay and molecular docking studies with Autodock 4.2.3 program were conducted. Results: Triazineamide 7c was assessed as a potent, selective and mixed-type dual inhibitor of acetylcholinesterase, with and IC50 of 5.306±0.002μM, by binding simultaneously with the catalytic active and peripheral anionic sites of acetylcholinesterase, and it had strong 2,2-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging abilities. Conclusion: These results suggest that triazineamides may be of interest to establish a structural basis for new anti-Alzheimer's disease agents.
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