College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeoungeup, Jeollabuk-do 56212, Republic of Korea.
Food Chem. 2018 Aug 15;257:128-134. doi: 10.1016/j.foodchem.2018.03.013. Epub 2018 Mar 6.
α-Glucosidase is an enzyme that plays a key role in raising blood sugar level and is considered a good target for developing drugs to treat type 2 diabetes. This study was performed to evaluate the inhibition of the catalytic reaction of α-glucosidase by minor phlorotannin derivatives (1-5) from Ecklonia cava. These derivatives demonstrated inhibitory activity, with IC values ranging from 2.3 ± 0.1 to 59.8 ± 0.8 μM. Among the phlorotannins identified, compounds 2 and 3-5 were revealed to be non-competitive and competitive inhibitors, respectively. Furthermore, a fluorescence-quenching study of receptor-ligand binding was performed to calculate the kinetic parameters (Ksv, Kq, and K). These signal data indicated a 1:1 ratio of ligand-receptor binding. The binding conformations of the phlorotannin ligands were visually solved through molecular simulation. In conclusion, these minor phlorotannins may serve as α-glucosidase inhibitors targeted for the treatment of type 2 diabetes.
α-葡萄糖苷酶是一种在提高血糖水平方面发挥关键作用的酶，被认为是开发治疗 2 型糖尿病药物的良好靶点。本研究旨在评估来自昆布属的微量岩藻多酚衍生物（1-5）对 α-葡萄糖苷酶催化反应的抑制作用。这些衍生物表现出抑制活性，IC 值范围为 2.3 ± 0.1 至 59.8 ± 0.8 μM。在所鉴定的岩藻多酚中，化合物 2 和 3-5 分别被证实为非竞争性和竞争性抑制剂。此外，还进行了受体-配体结合的荧光猝灭研究，以计算动力学参数（Ksv、Kq 和 K）。这些信号数据表明配体-受体结合的比例为 1:1。通过分子模拟直观地解决了岩藻多酚配体的结合构象。总之，这些微量岩藻多酚可能作为 2 型糖尿病治疗的 α-葡萄糖苷酶抑制剂。
