Lin Jing, Liang Qi-Ming, Ye Yuan-Na, Xiao Di, Lu Li, Li Meng-Yue, Li Jian-Ping, Zhang Yu-Fei, Xiong Zhuang, Feng Na, Li Chen
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.
Front Chem. 2022 Jun 23;10:928295. doi: 10.3389/fchem.2022.928295. eCollection 2022.
α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. To develop novel α-glucosidase inhibitors, a series of 5-fluoro-2-oxindole derivatives ( ∼ ) were synthesized, and their α-glucosidase inhibitory activities were investigated. Biological assessment results showed that most synthesized compounds presented potential inhibition on α-glucosidase. Among them, compounds , , and exhibited much better inhibitory activity with IC values of 49.89 ± 1.16 μM, 35.83 ± 0.98 μM, and 56.87 ± 0.42 μM, respectively, which were about 10 ∼ 15 folds higher than acarbose (IC = 569.43 ± 43.72 μM). A kinetic mechanism study revealed that compounds , , and inhibited the α-glucosidase in a reversible and mixed manner. Molecular docking was carried out to simulate the affinity between the compound and α-glucosidase.
已知α-葡萄糖苷酶抑制剂可阻止碳水化合物的消化，并降低碳水化合物对血糖的影响。为开发新型α-葡萄糖苷酶抑制剂，合成了一系列5-氟-2-氧代吲哚衍生物（～），并研究了它们的α-葡萄糖苷酶抑制活性。生物学评估结果表明，大多数合成化合物对α-葡萄糖苷酶具有潜在抑制作用。其中，化合物、和表现出更好的抑制活性，IC值分别为49.89±1.16 μM、35.83±0.98 μM和56.87±0.42 μM，比阿卡波糖（IC = 569.43±43.72 μM）高约10～15倍。动力学机制研究表明，化合物、和以可逆和混合方式抑制α-葡萄糖苷酶。进行了分子对接以模拟化合物与α-葡萄糖苷酶之间的亲和力。
