Pharmacognosy Research Group, Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Malaysia.
Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh.
Molecules. 2020 Dec 12;25(24):5885. doi: 10.3390/molecules25245885.
Jack has traditionally been used to treat diabetes. Despite its potential, the scientific proof in relation to this plant is still lacking. Thus, the present study aimed to investigate the -glucosidase inhibitors in leaf extracts using a metabolomics approach and to elucidate the ligand-protein interactions through in silico techniques. The plant leaves were extracted with methanol and water at five various ratios (100, 75, 50, 25 and 0% ; water-methanol). Each extract was tested for -glucosidase inhibition, followed by analysis using liquid chromatography tandem to mass spectrometry. The data were further subjected to multivariate data analysis by means of an orthogonal partial least square in order to correlate the chemical profile and the bioactivity. The loading plots revealed that the signals correspond to the activity of -glucosidase inhibitors, which led to the identification of three putative bioactive compounds, namely 5'-hydroxymethyl-1'-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-) quinazolin-1-yl)-heptan-1'-one (), -terpinyl--glucoside (), and machaeridiol-A (). Molecular docking of the identified inhibitors was performed using Auto Dock Vina software against the crystal structure of isomaltase (Protein Data Bank code: 3A4A). Four hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, and GLU411. Compound , , and showed binding affinity values of -8.3, -7.6, and -10.0 kcal/mol, respectively, which indicate the good binding ability of the compounds towards the enzyme when compared to that of quercetin, a known -glucosidase inhibitor. The three identified compounds that showed potential binding affinity towards the enzymatic protein in molecular docking interactions could be the bioactive compounds associated with the traditional use of this plant.
杰克传统上被用于治疗糖尿病。尽管有这种潜力，但与这种植物相关的科学证据仍然缺乏。因此，本研究旨在使用代谢组学方法研究叶提取物中的 -葡萄糖苷酶抑制剂，并通过计算技术阐明配体-蛋白相互作用。植物叶用甲醇和水在五个不同比例（100、75、50、25 和 0%；水-甲醇）提取。每个提取物均进行 -葡萄糖苷酶抑制测试，然后使用液相色谱串联质谱进行分析。数据通过正交偏最小二乘法进行多元数据分析，以关联化学特征和生物活性。加载图显示，信号对应于 -葡萄糖苷酶抑制剂的活性，这导致鉴定出三种可能的生物活性化合物，即 5'-羟甲基-1'-(1,2,3,9-四氢-吡咯并[2,1-]喹唑啉-1-基）-庚烷-1'-酮（）、-松油基--葡萄糖苷（）和大戟醇-A（）。使用 Auto Dock Vina 软件对鉴定出的抑制剂进行分子对接，对接物为异麦芽糖酶（蛋白数据库代码：3A4A）的晶体结构。在对接复合物中检测到四个氢键，涉及几个残基，即 ASP352、ARG213、ARG442、GLU277、GLN279、HIE280 和 GLU411。化合物 、 和 的结合亲和力值分别为-8.3、-7.6 和-10.0 kcal/mol，表明与已知的 -葡萄糖苷酶抑制剂槲皮素相比，这些化合物与酶具有良好的结合能力。在分子对接相互作用中显示出对酶的潜在结合亲和力的三种鉴定化合物可能是与该植物的传统用途相关的生物活性化合物。
