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 Alzheimer's disease (AD) patients, cholinesterase inhibitors are currently the most specified drug category for the remediation of AD.


METHOD
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.


RESULTS AND CONCLUSION
All the investigated dicarbonyl compounds exerted none or lower than 30% inhibition against both cholinesterases, whereas compounds 2, 8 and 11 showed 37, 42, 41% of inhibition towards 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 harmonization with experimental data.
['Hadda|Taibi Ben|TB|', 'Rauf|Abdur|A|', 'Zgou|Hsaine|H|', 'Senol|Fatma Sezer|FS|', 'Orhan|Ilkay Erdogan|IE|', 'Mabkhot|Yahia Nasser|YN|', 'Althagafi|Ismail I|II|', 'Farghaly|Thoraya A|TA|', 'Alterary|Seham|S|']
D000110:Acetylcholinesterase D000544:Alzheimer Disease D002091:Butyrylcholinesterase D002800:Cholinesterase Inhibitors D000077318:Density Functional Theory D015195:Drug Design D004797:Enzyme-Linked Immunosorbent Assay D006801:Humans D008958:Models, Molecular
in vitro Alzheimer’s disease (AD) DFT calculations Petra/Osiris/
Molinspiration (POM) analysis cholinesterase inhibition β-Amino dicarbonyl.