Yang Ting, Yang Zichen, Pan Fei, Jia Yijia, Cai Shengbao, Zhao Liang, Zhao Lei, Wang Ou, Wang Chengtao
Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China.
Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China.
Foods. 2022 Dec 14;11(24):4046. doi: 10.3390/foods11244046.
Postprandial hyperglycemia can be reduced by inhibiting α-glucosidase activity. Common α-glucosidase inhibitors such as acarbose may have various side effects. Therefore, it is important to find natural products that are non-toxic and have high α-glucosidase-inhibitory activity. In the present study, a comprehensive computational analysis of 27 dietary flavonoid compounds with α-glucosidase-inhibitory activity was performed. These included flavonoids, flavanones, isoflavonoids, dihydrochalcone, flavan-3-ols, and anthocyanins. Firstly, molecular fingerprint similarity clustering analysis was performed on the target molecules. Secondly, multiple linear regression quantitative structure-activity relationship (MLR-QSAR) models of dietary flavonoids (2D descriptors and 3D descriptors optimized), with R of 0.927 and 0.934, respectively, were constructed using genetic algorithms. Finally, the MolNatSim tool based on the COCONUT database was used to match the similarity of each flavonoid in this study, and to sequentially perform molecular enrichment, similarity screening, and QSAR prediction. After screening, five kinds of natural product molecule (2-(3,5-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one, norartocarpetin, 2-(2,5-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one, 2-(3,4-dihydroxyphenyl)-5-hydroxy-4H-chromen-4-one, and morelosin) were finally obtained. Their IC values were 8.977, 31.949, 78.566, 87.87, and 94.136 µM, respectively. Pharmacokinetic predictions evaluated the properties of the new natural products, such as bioavailability and toxicity. Molecular docking analysis revealed the interaction of candidate novel natural flavonoid compounds with the amino acid residues of α-glucosidase. Molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MMGBSA) further validated the stability of these novel natural compounds bound to α-glucosidase. The present findings may provide new directions in the search for novel natural α-glucosidase inhibitors.
通过抑制α-葡萄糖苷酶活性可以降低餐后高血糖。常见的α-葡萄糖苷酶抑制剂如阿卡波糖可能有各种副作用。因此，寻找无毒且具有高α-葡萄糖苷酶抑制活性的天然产物很重要。在本研究中，对27种具有α-葡萄糖苷酶抑制活性的膳食黄酮类化合物进行了全面的计算分析。这些包括黄酮类、黄烷酮类、异黄酮类、二氢查耳酮、黄烷-3-醇类和花青素类。首先，对目标分子进行分子指纹相似性聚类分析。其次，使用遗传算法构建了膳食黄酮类化合物（优化的二维描述符和三维描述符）的多元线性回归定量构效关系（MLR-QSAR）模型，其R值分别为0.927和0.934。最后，使用基于COCONUT数据库的MolNatSim工具匹配本研究中每种黄酮类化合物的相似性，并依次进行分子富集、相似性筛选和QSAR预测。筛选后，最终获得了五种天然产物分子（2-(3,5-二羟基苯基)-5,7-二羟基-4H-色原酮、去甲波罗蜜黄素、2-(2,5-二羟基苯基)-5,7-二羟基-4H-色原酮、2-(3,4-二羟基苯基)-5-羟基-4H-色原酮和莫雷洛辛）。它们的IC值分别为8.977、31.949、78.566、87.87和94.136μM。药代动力学预测评估了新天然产物的性质，如生物利用度和毒性。分子对接分析揭示了候选新型天然黄酮类化合物与α-葡萄糖苷酶氨基酸残基的相互作用。分子动力学（MD）模拟和分子力学/广义玻恩表面积（MMGBSA）进一步验证了这些新型天然化合物与α-葡萄糖苷酶结合的稳定性。本研究结果可能为寻找新型天然α-葡萄糖苷酶抑制剂提供新方向。
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