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黄酮糖苷作为乙酰胆碱酯酶抑制剂:计算和实验证据

Flavanone glycosides as acetylcholinesterase inhibitors: computational and experimental evidence.

作者信息

Remya C, Dileep K V, Tintu I, Variyar E J, Sadasivan C

机构信息

Department of Biotechnology and Microbiology and Inter University Centre for Bioscience, Kannur University, Thalassery Campus, Palayad-670 661, India.

出版信息

Indian J Pharm Sci. 2014 Nov-Dec;76(6):567-70.

Abstract

Acetylcholinesterase hydrolyzes the neurotransmitter called acetylcholine and is crucially involved in the regulation of neurotransmission. One of the observable facts in the neurodegenerative disorders like Alzheimer's disease is the decrease in the level of acetylcholine. Available drugs that are used for the treatment of Alzheimer's disease are primarily acetylcholinesterase inhibitors with multiple activities. They maintain the level of acetylcholine in the brain by inhibiting the acetylcholinesterase function. Hence acetylcholinesterase inhibitors can be used as lead compounds for the development of drugs against AD. In the present study, the binding potential of four flavanone glycosides such as naringin, hesperidin, poncirin and sakuranin against acetylcholinesterase was analysed by using the method of molecular modeling and docking. The activity of the top scored compound, naringin was further investigated by enzyme inhibition studies and its inhibitory concentration (IC50) towards acetylcholinesterase was also determined.

摘要

乙酰胆碱酯酶可水解神经递质乙酰胆碱,对神经传递的调节至关重要。在阿尔茨海默病等神经退行性疾病中可观察到的一个事实是乙酰胆碱水平降低。目前用于治疗阿尔茨海默病的药物主要是具有多种活性的乙酰胆碱酯酶抑制剂。它们通过抑制乙酰胆碱酯酶的功能来维持大脑中乙酰胆碱的水平。因此,乙酰胆碱酯酶抑制剂可作为开发抗阿尔茨海默病药物的先导化合物。在本研究中,采用分子建模和对接方法分析了柚皮苷、橙皮苷、枳属苷和樱花苷四种黄酮苷对乙酰胆碱酯酶的结合潜力。通过酶抑制研究进一步考察了得分最高的化合物柚皮苷的活性,并测定了其对乙酰胆碱酯酶的抑制浓度(IC50)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb97/4293693/16308ee6a6df/IJPhS-76-567-g001.jpg

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