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

Abstract

A library of N-benzylpyridinium-based compounds, 7a-j and 8a-j, was designed and synthesised as potential acetylcholinesterase) AChE (inhibitors. An in vitro assay for the synthesised compounds showed that most compounds had significant AChE inhibitory activities at the nanomolar and submicromolar levels. The benzyl (8a) and fluoro (8b) derivatives were the most active, with IC₅₀ values ≤56 nM. Compound 7f, which had a benzyl moiety, showed the highest potency among all the target compounds, with an IC₅₀ value of 7.5 ± 0.19 nM against AChE, which was higher than that of the activities of tacrine (IC₅₀ = 30 ± 0.2 nM) and donepezil (IC₅₀ = 14 ± 0.12 nM). Compounds with vanillin moieties exhibited antioxidant activity. Among the tested compounds, four derivatives (7f, 7 g, 8f, and 8 g) exhibited superior AChE inhibitory activity, with K_i 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.

GRAPHICAL ABSTRACT

Keywords:

• Acetylcholinesterase inhibitors
• antioxidants
• Alzheimer’s disease
• docking study
• synthesis
• pyridinium

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The authors accept the final version of the paper submitted to the journal.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors gratefully acknowledge the financial support from GJU (project: SAMS-01/2018) for conducting this work.