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

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Author(s): Taibi Ben Hadda, Abdur Rauf, Hsaine Zgou, Fatma Sezer Senol, Ilkay Erdogan Orhan, Yahia Nasser Mabkhot*, Ismail I. Althagafi, Thoraya A. Farghaly*.

Journal Name: Mini-Reviews in Medicinal Chemistry

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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. 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. 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.

Keywords: β-Amino dicarbonyl, cholinesterase inhibition, Alzheimer’s disease (AD), DFT calculations, Petra/ Osiris/ Molinspiration (POM) analyses.

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(E-pub Ahead of Print)
DOI: 10.2174/1389557518666181102102816
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