Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
Faculty of Chemical &Environmental Engineering, Wuyi University, Jiangmen, 529020, China.
Sci Rep. 2017 Mar 30;7:45578. doi: 10.1038/srep45578.
Ursolic acid (UA) is a major pentacyclic triterpenoid in plants, vegetables and fruits, which has been reported to have a potential anti-diabetic activity. Despite various semi-synthetic ursolic acid derivatives already described, new derivatives still need to be designed and synthesized to further improve the anti-diabetic activity. In the present study, two series of novel UA derivatives, were synthesized and their structures were confirmed. The enzyme inhibition activities of semi-synthesized analogues against α-glucosidase were screened in vitro. The results indicated that most of UA derivatives showed a significant inhibitory activity, especially analogues UA-O-i with the IC values of 0.71 ± 0.27 μM, which was more potential than other analogues and the positive control. Furthermore, molecular docking studies were also investigated to verify the in vitro study. Structure modification at the C-3 and C-2 positions of UA was an effective approach to obtain the desired ligand from UA, whose structure was in accordance with the active pocket. Besides, suitable hydrophobic group at the position of C-2 might play an important role for the docking selectivity and binding affinity between the ligand and the homology modelling protein. These results could be helpful for designing more potential α-glucosidase inhibitors from UA in the future.
熊果酸（UA）是植物、蔬菜和水果中的一种主要五环三萜类化合物，据报道具有潜在的抗糖尿病活性。尽管已经描述了各种半合成熊果酸衍生物，但仍需要设计和合成新的衍生物，以进一步提高抗糖尿病活性。在本研究中，合成了两种新型 UA 衍生物系列，并确证了它们的结构。在体外筛选了半合成类似物对α-葡萄糖苷酶的酶抑制活性。结果表明，大多数 UA 衍生物表现出显著的抑制活性，特别是 UA-O-i 类似物的 IC 值为 0.71±0.27μM，比其他类似物和阳性对照更有潜力。此外，还进行了分子对接研究以验证体外研究。UA 上 C-3 和 C-2 位置的结构修饰是从 UA 获得所需配体的有效方法，其结构与活性口袋一致。此外，C-2 位置合适的疏水基团可能在配体与同源建模蛋白之间的对接选择性和结合亲和力中发挥重要作用。这些结果可能有助于未来从 UA 设计更多潜在的α-葡萄糖苷酶抑制剂。
