Synthesis, biological evaluation, and computational studies of N -benzyl pyridinium-curcumin derivatives as potent AChE inhibitors with antioxidant activity

• Published in: Journal of enzyme inhibition and medicinal chemistry 2023-12, Vol.38 (1), p.2281264-2281264
• Main Authors: Al-Rifai, Nafisah M, Al-Khalileh, Nemeh M, Zahra, Jalal A, El-Barghouthi, Musa I, Darras, Fouad H
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Acetylcholinesterase inhibitors; Alzheimer Disease; Alzheimer’s disease; Antioxidants; Antioxidants - pharmacology; Cholinesterase Inhibitors - pharmacology; Curcumin; docking study; Donepezil; Humans; Molecular Docking Simulation; Pain; Pyridinium; Structure-Activity Relationship; synthesis; Tacrine; Vanillin
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2023.2281264

A library of -benzylpyridinium-based compounds, and , was designed and synthesised as potential acetylcholinesterase) AChE (inhibitors. An assay for the synthesised compounds showed that most compounds had significant AChE inhibitory activities at the nanomolar and submicromolar levels. The benzyl ( ) and fluoro ( ) derivatives were the most active, with IC values ≤56 nM. Compound which had a benzyl moiety, showed the highest potency among all the target compounds, with an IC value of 7.5 ± 0.19 nM against AChE, which was higher than that of the activities of tacrine (IC = 30 ± 0.2 nM) and donepezil (IC = 14 ± 0.12 nM). Compounds with vanillin moieties exhibited antioxidant activity. Among the tested compounds, four derivatives ( , , and ) exhibited superior AChE inhibitory activity, with values of 6-16 nM, which were potent in the same range as the approved drug, donepezil. These compounds showed moderate antioxidant activities, as indicated by the results of the ABTS assay.