Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Nat Prod Res. 2021 May;35(9):1436-1444. doi: 10.1080/14786419.2019.1655017. Epub 2019 Aug 21.
Ten pentacyclic triterpenes (-) were isolated from We evaluated their -glucosidase inhibitory activity, and found that the aglycones, , , , and showed superior IC values to the positive control. In order to explain the structural requirements for -glucosidase inhibitory activity, eleven derivatives were prepared, including one new compound, 2-formyl-(A)1-19-hydroxy-1-norursane-2, 12-dien-28-oic acid . The results demonstrated that a free hydroxyl at ring-A and a free carboxylic group at position 28 are key structural features for the α-glucosidase inhibitory activity, also that an ursane skeleton is optimum for the activity. Additionally, enzyme kinetic analysis of pomolic acid , the most potent compound, revealed that it inhibited -glucosidase in a mixed-type manner. The molecular docking simulation validated this type of inhibition and highlighted the role of the C-3 hydroxyl and C-28 carboxylic groups in interaction with the enzyme .
从 中分离得到 10 个五环三萜（-）。我们评估了它们的 -葡萄糖苷酶抑制活性，发现糖苷配基 、 、 、 和 对 -葡萄糖苷酶的抑制活性优于阳性对照。为了解释 -葡萄糖苷酶抑制活性的结构要求，我们制备了 11 个衍生物，包括一个新化合物 2-甲酰基-（A）1-19-羟基-1-降乌苏烷-2,12-二烯-28-酸。结果表明，A 环上的游离羟基和 28 位上的游离羧基是 -葡萄糖苷酶抑制活性的关键结构特征，熊烷骨架对活性是最佳的。此外，对最有效化合物pomolic 酸的酶动力学分析表明，它以混合抑制方式抑制 -葡萄糖苷酶。分子对接模拟验证了这种抑制类型，并强调了 C-3 羟基和 C-28 羧基在与酶相互作用中的作用。
