Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies

被引:29
|
作者
Mughal, Ehsan Ullah [1 ]
Sadiq, Amina [2 ]
Ashraf, Jamshaid [1 ]
Zafar, Muhammad Naveed [3 ]
Sumrra, Sajjad Hussain [1 ]
Tariq, Rubina [2 ]
Mumtaz, Amara [4 ]
Javid, Asif [1 ]
Khan, Bilal Ahmad [5 ]
Ali, Anser [6 ]
Javed, Chaudhary Omer [2 ]
机构
[1] Univ Gujrat, Dept Chem, Gujrat 50700, Pakistan
[2] Govt Coll Women Univ, Dept Chem, Siancot 51300, Pakistan
[3] Quaid I Asam Univ, Dept Chem, Islamabad 45320, Pakistan
[4] COMSATS Univ Islamabad, Dept Chem, Abbottabad Campus, Abbottabad 22060, Pakistan
[5] Univ Azad Jammu & Kashmir, Dept Chem, Muzaffarabad, Pakistan
[6] Mirpur Univ Sci & Technol, Dept Zool, Mirpur 10250, Pakistan
关键词
Flavonoids; Flavonols; 3-hydroxyflavones; 4-thioflavonols; Sulfur compounds; Cholinesterases; AChE/BChE inhibitors; Molecular docking studies; BIOLOGICAL EVALUATION; DERIVATIVES;
D O I
10.1016/j.bioorg.2019.103124
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, H-1-, C-13 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.
引用
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页数:11
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