Innovative cholinergic scaffolds, synthesis, and characterization of substituted 1,2,4-triazole-3-ylthio-N-acetamides and their in silico studies: supplement against neurodegenerative disease

• Published in: Journal of the Iranian Chemical Society
• Main Author: Arfan M.; Siddiqui S.Z.; Abbasi M.A.; Aziz-ur-Rehman; Saad S.M.; Shah S.A.A.; Ashraf M.; Hussain S.; Ali F.; Solangi M.; Khan K.M.
• Format: Article
• Language: English
• Published: Springer Science and Business Media Deutschland GmbH 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85146939634&doi=10.1007%2fs13738-023-02756-3&partnerID=40&md5=964e63cd5f3e44fdde72cacf73cc905d

Neurodegeneration is an unfortunate condition associated with the steady loss of structures and functions of neurons. The most common complication that arises from neurodegenerative disorder is Alzheimer’s disease, which occurs due to hyperactivities of the responsible enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). We synthesized a series of medicinally important 1,2,4-triazole-3-ylthio-N-acetamides serving AChE and BChE inhibitors to cope with this stressful condition. The promising results were found, especially for the synthetic compound 2-((4-ethyl-5-(4′-methoxyphenyl)-4H-1,2,4-triazole-3-yl)thio)-N-(3′′,5′′-dimethyl phenyl)acetamide (8j) against AChE and 2-((4-ethyl-5-(4′-methoxyphenyl)-4H-1,2,4-triazole-3-yl)thio)-N-(3′′,4′′-dimethyl phenyl)acetamide (8i) against BChE, using eserine as standard. Molecular docking analyses were also performed to gain insight into the molecules’ interactions with the active sites of the enzymes. All the synthetic compounds were characterized by spectroscopic techniques such as 1H-NMR, 13C-NMR, FTIR, and EIMS. Graphical abstract: [Figure not available: see fulltext.] © 2023, Iranian Chemical Society.