Neuroprotective potential of synthesized coumarin-based glycinate and heterocyclic amide derivatives: an acetylcholinesterase inhibition study

Abstract

Selenium nanoparticles (Se-NPs) were manufactured effectively by a green chemical reduction approach utilizing sodium selenite and ascorbic acid, resulting in stable, rod-like nanoparticles with an average particle size of 23.5 nm and a high surface area of 25.05 m²/g. These Se-NPs were utilized as effective nanocatalysts in the chemical synthesis of new coumarin-based glycinate and heterocyclic amide derivatives via esterification and nucleophilic substitution reactions, markedly improving reaction rates and yields relative to traditional approaches. The resultant organic compounds (C1, C2, C6, C8, C9) were subsequently immobilized onto Se-NPs, resulting in stable core-shell nanostructures, as verified by UV-Vis spectroscopy and TEM imaging. The structural elucidation of the produced compounds was conducted utilizing FTIR, ¹H NMR, and ¹³C NMR spectroscopy. The acetylcholinesterase (AChE) inhibitory assay revealed that C6 (IC₅₀ = 8.0 ± 0.24 µM) and C9-Se-NPs (IC₅₀ = 1.19 ± 0.04 µM) exhibited enhanced inhibitory activity compared to the standard drug (IC₅₀ = 11.41 ± 0.35 µM), whereas C8 showed a higher IC₅₀ value (13.0 ± 0.54 µM), indicating lower activity. Upon nanoparticle conjugation, a significant reduction in IC₅₀ was observed for C6 (from 8.0 ± 0.24 to 4.64 ± 0.14 µM) and C8 (from 13.0 ± 0.54 to 5.272 ± 0.161 µM). Although C9-Se-NPs (1.19 ± 0.04 µM) exhibited a higher IC₅₀ than the parent compound C9 (0.50 ± 0.01 µM), it remained markedly more potent than all other tested compounds in both free and nano-conjugated forms. Overall, these findings suggest that Se-NPs act as effective nanocatalysts for organic transformations and as efficient carriers that enhance the biological activity of the conjugated compounds, supporting their potential application as multifunctional platforms for neuroprotective therapy in Alzheimer's disease.