College of Science, Yunnan Agricultural University, Kunming 650201, China.
Yunnan Key Laboratory of Biomass Big Data, Yunnan Agricultural University, Kunming 650201, China.
Molecules. 2020 Jan 2;25(1):189. doi: 10.3390/molecules25010189.
Lam. (MO) is called the "Miracle Tree" because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound ) had the highest activity (half-maximal inhibitory concentration [IC] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.
辣木（MO）因其广泛的药理活性而被称为“奇迹之树”。除了作为一种重要的食物外，它在亚洲传统医学中还被长期用于治疗糖尿病和肥胖等慢性疾病。在这项研究中，通过构建 MO 植物化学成分文库，并使用 Discovery Studio 软件，对化合物进行了与抑制二肽基肽酶（DPP-IV）相关的虚拟筛选和分子对接实验，DPP-IV 是治疗 2 型糖尿病的一个重要靶点。经过涉及筛选类药性化合物、预测药物吸收、分布、代谢、排泄和毒性（ADME/T）的药代动力学特性、LibDock 热图匹配分析和 CDOCKER 分子对接分析的四步筛选过程，鉴定出三种可能的 DPP-IV 抑制剂 MO 成分，并分析了它们的对接模式。体外活性验证表明，三种 MO 成分均具有一定的 DPP-IV 抑制活性，其中 O-乙基-4-[(α-L-鼠李糖氧基）-苄基]氨基甲酸酯（化合物 ）具有最高的活性（半抑制浓度 [IC] = 798 nM）。这项研究为探索 MO 抗糖尿病活性的分子机制提供了参考。所得的 DPP-IV 抑制剂可用于结构优化和深入的体内评价。
