Zhu Hua, Zhong Xin
School of Chemistry and Chemical Engineering, Mianyang Teacher's College, Mianyang, China.
Dean's Office, Mianyang Teacher's College, Mianyang, China.
Front Chem. 2022 Nov 15;10:1041328. doi: 10.3389/fchem.2022.1041328. eCollection 2022.
Six flavonoid derivatives were synthesized and tested for anti--glucosidase activities. All derivatives were confirmed using NMR and HRMS and exhibited excellent inhibitory effects on -glucosidase. Derivative exhibited the highest anti--glucosidase activity (IC: 15.71 ± 0.21 μM). Structure-activity relationship results showed that bromine group would be the most beneficial group to anti--glucosidase activity. Inhibitory mechnism and inhibition kinetics results showed derivative was a reversible and mixed-type inhibitor. Molecular docking revealed that derivative was tightly bind to the amino acid residues of active pocket of α-glucosidase and formed hydrogen bond, π-π stacking, and Pi-Donor hydrogen with α-glucosidase. Moreover, the physicochemical parameters of all derivatives were assessed using SwissADME software. This results also showed that the hybridization of flavonoid and phenylpropionic acid would be a useful strategy for the development of -glucosidase inhibitors.
合成了六种黄酮类衍生物，并测试了它们的抗葡萄糖苷酶活性。所有衍生物均通过核磁共振（NMR）和高分辨率质谱（HRMS）进行了确证，并且对葡萄糖苷酶表现出优异的抑制作用。衍生物表现出最高的抗葡萄糖苷酶活性（IC：15.71±0.21μM）。构效关系结果表明，溴基团对抗葡萄糖苷酶活性最为有利。抑制机制和抑制动力学结果表明，衍生物是一种可逆的混合型抑制剂。分子对接显示，衍生物与α-葡萄糖苷酶活性口袋的氨基酸残基紧密结合，并与α-葡萄糖苷酶形成氢键、π-π堆积和Pi-供体氢键。此外，使用SwissADME软件评估了所有衍生物的理化参数。该结果还表明，黄酮类与苯丙酸的杂合将是开发葡萄糖苷酶抑制剂的一种有用策略。
