Inhibitory Effects of Novel 7-Substituted 6-iodo-3- O -Flavonol Glycosides against Cholinesterases and β-secretase Activities, and Evaluation for Potential Antioxidant Properties

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-09, Vol.24 (19), p.3500
• Main Authors: Agbo, Emmanuel N, Gildenhuys, Samantha, Mphahlele, Malose J
• Format: Article
• Language: English
• Subjects: 3-o-flavonol glycosides; Acetylcholinesterase; Alzheimer's disease; Amyloid Precursor Protein Secretases - antagonists & inhibitors; Amyloid Precursor Protein Secretases - chemistry; antioxidant assay; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacology; Binding Sites; butyrylcholinesterase; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Donepezil; Dose-Response Relationship, Drug; Drugs; Enzyme Activation - drug effects; Enzymes; Flavonoids; Flavonols; Flavonols - chemistry; Glycosides; Glycosides - chemistry; Glycosides - pharmacology; Inhibitory Concentration 50; kinetic studies; Kinetics; Ligands; Models, Molecular; Molecular Conformation; Molecular docking; Molecular Structure; NMR; Nuclear magnetic resonance; Protein Binding; Scavenging; Secretase; Structure-Activity Relationship; Substitutes; x-ray; β-secretase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24193500

A series of 7-halogeno- (X = F, Cl, Br) and 7-methoxy-substituted acetylated 6-iodo-3- -flavonol glycosides were prepared, and evaluated for inhibitory effect in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. 7-Bromo-2-(4-chlorophenyl)-6-iodo-4 -chromen-4-one-3- -2,3,4,6 -tetraacetyl-β- -glucopyranoside ( ) and 7-bromo-6-iodo-2-(4-methoxyphenyl)-4 -chromen-4-one-3- -2,3,4,6- -tetraacetyl-β- -glucopyranoside ( ) exhibited significant inhibitory effect against AChE activity when compared to the activity of the reference standard, donepezil. Compound was found to be selective against AChE and to exhibit reduced inhibitory effect against BChE activity. 6-Iodo-7-methoxy-2-(4-methoxyphenyl)-4 -chromen-4-one-3- -2,3,4,6- -tetraacetyl-β- -glucopyranoside ( ) was found to exhibit increased activity against BChE, more so than the activity of donepezil. The most active compounds were also evaluated for inhibitory effect against β-secretase activity and for potential radical scavenging activities. The experimental data were complemented with molecular docking (in silico) studies of the most active compounds into the active sites of these enzymes.