Das Subrata, Laskar Monjur A, Sarker Satyajit D, Choudhury Manabendra D, Choudhury Prakash Roy, Mitra Abhijit, Jamil Shajarahtunnur, Lathiff Siti Mariam A, Abdullah Siti Awanis, Basar Norazah, Nahar Lutfun, Talukdar Anupam D
Department of Life Science and Bioinformatics, Assam University, Silchar, 788011, Assam, India.
Bioinformatics Centre, Assam University, Silchar, 788011, Assam, India.
Phytochem Anal. 2017 Jul;28(4):324-331. doi: 10.1002/pca.2679. Epub 2017 Feb 7.
Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease.
The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.
Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.
In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC was predicted as 6.025 nM.
Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.
波罗蜜属（Artocarpus J. R. Forster & G. Forster）的异戊烯化和吡喃黄酮类化合物以其乙酰胆碱酯酶（AChE）抑制、抗胆碱能、抗炎、抗菌、抗氧化、抗增殖和酪氨酸酶抑制活性而闻名。其中一些化合物还被证明对阿尔茨海默病有效。
本计算机模拟研究的目的是建立方案，以预测异戊烯化和吡喃黄酮类中对AChE抑制最有效的黄酮类化合物，这与阿尔茨海默病的潜在治疗相关。
选择从窄叶波罗蜜（Artocarpus anisophyllus Miq.）中分离出的三种黄酮类化合物进行研究。对这些化合物进行了计算机模拟的Lipinski筛选、ADME/Tox筛选、分子对接和定量构效关系（QSAR）分析。基于Ellman法通过生物活性染色评估体外活性。
在Lipinski筛选和ADME/Tox筛选中，所有测试化合物均产生阳性结果，但在靶点垂钓中，只有一种黄酮类化合物能够成功靶向AChE。对该黄酮类化合物进行了分子对接，该化合物的评分为-13.5762。通过QSAR分析，发现IC50为1659.59 nM。再次，从母体化合物生成了100种衍生物并进行对接。衍生物化合物20得分最高，即-31.6392，预测IC50为6.025 nM。
结果表明黄酮类化合物可能是AChE的有效抑制剂，因此可用于阿尔茨海默病的治疗。版权所有© 2017 John Wiley & Sons, Ltd.
