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.

Arfan, Muhammad; Siddiqui, Sabahat Zahra; Abbasi, Muhammad Athar; Aziz-ur-Rehman; Saad, Syed Muhammad; Shah, Syed Adnan Ali; Ashraf, Muhammad; Hussain, Safdar; Ali, Farman; Solangi, Mehwish; Khan, Khalid Mohammed

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.

NEURODEGENERATION; BINDING sites; ALZHEIMER'S disease; ACETAMIDE derivatives; MOLECULAR docking; BUTYRYLCHOLINESTERASE

Journal of the Iranian Chemical Society, 2023, Vol 20, Issue 6, p1307

1735-207X

Academic Journal

10.1007/s13738-023-02756-3