Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies.
To explore new scaffolds for the treat of Alzheimer's disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1H-, 13C NMR) and mass spectrometry (EI-MS). All the derivatives (1-24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes.
['Mughal|Ehsan Ullah|EU|', 'Sadiq|Amina|A|', 'Ashraf|Jamshaid|J|', 'Zafar|Muhammad Naveed|MN|', 'Sumrra|Sajjad Hussain|SH|', 'Tariq|Rubina|R|', 'Mumtaz|Amara|A|', 'Javid|Asif|A|', 'Khan|Bilal Ahmad|BA|', 'Ali|Anser|A|', 'Javed|Chaudhary Omer|CO|']
D000110:Acetylcholinesterase D002091:Butyrylcholinesterase D020134:Catalytic Domain D002800:Cholinesterase Inhibitors D044948:Flavonols D006801:Humans D062105:Molecular Docking Simulation D015394:Molecular Structure D011485:Protein Binding D013329:Structure-Activity Relationship
Flavonols 4-thioflavonols Molecular docking studies Cholinesterases 3-hydroxyflavones AChE/BChE inhibitors Flavonoids Sulfur compounds