Resveratrol-inspired methoxy-substituted pyrrolidine- and morpholine-based carbamates bearing oxazole or benzimidazole moieties were synthesized and evaluated for their cholinesterase-inhibitory and anti-inflammatory activities. A series of twelve compounds (1–12) was prepared and structurally characterized using spectroscopic methods. Their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined using a modified Ellman assay, while anti-inflammatory activity was assessed by measuring TNF-α production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells. The investigated compounds selectively inhibited BChE, while showing weak or negligible inhibition of AChE. Pyrrolidine-based oxazole carbamate 1 exhibited the highest BChE inhibitory potency (IC₅₀ = 0.09 μM), approximately 25-fold greater than standard rivastigmine. Compound 1 was also the only tested derivative to concentration-dependently inhibit TNF-α production (IC₅₀ = 4.3 μM) without affecting cell viability. Molecular docking of compounds 1 and 9, the best pyrrolidine- and morpholine-based carbamates, indicated that both fit within the BChE active-site gorge through extensive aromatic, hydrophobic, and polar interactions. Overall, the results identify compound 1 as a promising multifunctional lead for further investigation of the relationship between cholinesterase inhibition and anti-inflammatory activity.

Resveratrol-inspired methoxy-substituted pyrrolidine- and morpholine-based carba-mates bearing oxazole or benzimidazole moieties were synthesized and evaluated for their cholinesterase-inhibitory and anti-inflammatory activities. A series of twelve compounds (1–12) was prepared and structurally characterized using spectroscopic methods. Their inhibitory activities against acetylcholinesterase (AChE) and butyryl-cholinesterase (BChE) were determined using a modified Ellman assay, while an-ti-inflammatory activity was assessed by measuring TNF-α production in lipopolysac-charide-stimulated human peripheral blood mononuclear cells. The investigated com-pounds selectively inhibited BChE, while showing weak or negligible inhibition of AChE. Pyrrolidine-based oxazole carbamate 1 exhibited the highest BChE inhibitory potency (IC₅₀ = 0.09 μM), approximately 25-fold greater than standard rivastigmine. Compound 1 was also the only tested derivative to concentration-dependently inhibit TNF-α production (IC₅₀ = 4.3 μM) without affecting cell viability. Molecular docking of compounds 1 and 9, the best pyrrolidine- and morpholine-based carbamates, indicated that both fit within the BChE active-site gorge through extensive aromatic, hydrophobic, and polar interactions. Overall, the results identify compound 1 as a promising multi-functional lead for further investigation of the relationship between cholinesterase in-hibition and anti-inflammatory activity.