Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, KPK, Pakistan.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Molecules. 2022 Aug 6;27(15):5004. doi: 10.3390/molecules27155004.
(1) Background: belongs to a highly reputed family of medicinal plants, with plant extract being used as medicine in indigenous system. However, limited data is available regarding the exploitation of the medicinal potential of isolated pure compounds from this family; (2) Methods: A whole plant extract was partitioned into fractions and on the basis of biological activity, an ethyl acetate fraction was selected for isolation of pure compounds. Isolated compounds were characterized using different spectroscopic techniques. The compounds isolated from this study were tested for their medicinal potential using in-vitro enzyme assay, coupled with in-silico studies; (3) Results: Three new acrylic acid derivatives (-) have been isolated from the ethyl acetate fraction of . The characterization of these compounds (-) was carried out using UV/Vis, FT-IR, 1D and 2D-NMR spectroscopy (H-NMR, C-NMR, HMBC, NOESY) and mass spectrometry. These acrylic acid derivatives were further evaluated for their enzyme inhibition potential against urease from jack bean and glucosidase from using both in-silico and in-vitro approaches. In-vitro studies showed that compound has the highest inhibition against urease enzyme (IC =10.46 ± 0.03 μΜ), followed by compound and compound with percent inhibition and IC value of 16.87 ± 0.02 c and 13.71 ± 0.07 μΜ, respectively, compared to the standard (thiourea-IC = 21.5 ± 0.01 μΜ). The investigated IC value of compound 3 against the urease enzyme is two times lower compared to thiourea, suggesting that this compound is twice as active compared to the standard drug. On the other hand, all three compounds (-) revealed mild inhibition potential against -glucosidase. In-silico molecular docking studies, in combination with MD simulations and free energy, calculations were also performed to rationalize their time evolved mode of interaction inside the active pocket. Binding energies were computed using a MMPBSA approach, and the role of individual residues to overall binding of the inhibitors inside the active pockets were also computed; (4) Conclusions: Together, these studies confirm the inhibitory potential of isolated acrylic acid derivatives against both urease and -glucosidase enzymes; however, their inhibition potential is better for urease enzyme even when compared to the standard.
(1)背景：属于一种声誉很高的药用植物家族，其植物提取物在本土体系中被用作药物。然而，关于从该家族中分离出的纯化合物的药用潜力的开发，可用的数据有限；(2)方法：对整个植物提取物进行分区，根据生物活性，选择乙酸乙酯部分进行纯化合物的分离。用不同的光谱技术对分离得到的化合物进行表征。对从这项研究中分离出来的化合物进行了测试，以评估其在体外酶测定中的药用潜力，同时结合了计算机模拟研究；(3)结果：从 的乙酸乙酯部分分离出三种新的丙烯酸衍生物(-)。这些化合物(-)的特征是通过紫外/可见分光光度法、傅立叶变换红外光谱法、1D 和 2D-NMR 光谱法（H-NMR、C-NMR、HMBC、NOESY）和质谱法进行的。进一步评估了这些丙烯酸衍生物对来自豆科植物的脲酶和来自 的 -葡萄糖苷酶的抑制潜力，使用了计算机模拟和体外方法。体外研究表明，化合物 对脲酶的抑制作用最强（IC=10.46±0.03μΜ），其次是化合物 和化合物 ，其抑制率和 IC 值分别为 16.87±0.02 c 和 13.71±0.07μΜ，与标准品（硫脲-IC=21.5±0.01μΜ）相比。与硫脲相比，化合物 3 对脲酶的抑制作用的 IC 值低了两倍，这表明该化合物的活性是标准药物的两倍。另一方面，三种化合物（-）对 -葡萄糖苷酶均显示出温和的抑制潜力。还进行了计算机模拟分子对接研究，结合 MD 模拟和自由能计算，以合理推断它们在活性口袋内的相互作用随时间的演变模式。使用 MMPBSA 方法计算结合能，还计算了单个残基在抑制剂与活性口袋整体结合中的作用；(4)结论：综上所述，这些研究证实了分离出的丙烯酸衍生物对脲酶和 -葡萄糖苷酶的抑制潜力；然而，它们的抑制潜力对脲酶更好，即使与标准品相比也是如此。
