Title:Drug Design of Inhibitors of Alzheimer’s Disease (AD): POM and DFT Analyses of Cholinesterase Inhibitory Activity of β-amino di-Carbonyl Derivatives
VOLUME: 18
Author(s):Taibi Ben Hadda, Abdur Rauf, Hsaine Zgou, Fatma Sezer Senol, Ilkay Erdogan Orhan, Yahia Nasser Mabkhot*, Ismail I. Althagafi and Thoraya A. Farghaly*
Affiliation:LCM, Department of Chemestry, Faculty of Sciences, University Mohammed Premier, Oujda 60000, Department of Geology, University of Swabi, Anbar 23561, Khyber Pakhtunkhwa, Ibn Zohr University, Polydisciplinary Faculty, Ouarzazate 45000, Department of Pharmacognosy, Pharmacy Faculty, Gazi University, Ankara 06330, Department of Pharmacognosy, Pharmacy Faculty, Gazi University, Ankara 06330, Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh-11451, Department of Chemistry, Umm Al-Qura University, Mecca, Department of Chemistry, Faculty of Science, University of Cairo, Giza
Keywords:β-Amino dicarbonyl, cholinesterase inhibition, Alzheimer’s disease (AD), DFT calculations, Petra/ Osiris/ Molinspiration (POM) analyses.
Abstract: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.
