Drug Design of Inhibitors of Alzheimer's Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives.

BACKGROUND: Since deficit of acetylcholine has been evidenced in the patients of Alzheimer's disease (AD), cholinesterase inhibitors are currently the most prescribed drug class for the treatment of AD.

RESULTS: In the present study, 16 compounds (1-16) with dicarbonyl skeletons have been synthesized and tested for their inhibitory potential in vitro against AChE and BChE using ELISA microtiter plate assays at 100 µg/mL. Since metal accumulation is related to AD, the compounds were also tested for their metal-chelation capacity.

CONCLUSIONS: All of the dicarbonyl compounds tested exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition toward BChE, being the most active. The highest metal-chelation capacity was observed with compound 8 (53.58 ± 2.06%). POM and DFT analyses are in good agreement with experimental data.