Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Sci Rep. 2023 Jun 2;13(1):8960. doi: 10.1038/s41598-023-36046-y.
Herein, various N'-substituted benzylidene benzohydrazide-1,2,3-triazoles were designed, synthesized, and screened for their inhibitory activity toward α-glucosidase. The structure of derivatives was confirmed using H- and C-NMR, FTIR, Mass spectrometry, and elemental analysis. All derivatives exhibited good inhibition with IC values in the range of 0.01 to 648.90 µM, compared with acarbose as the positive control (IC = 752.10 µM). Among them, compounds 7a and 7h showed significant potency with IC values of 0.02 and 0.01 µM, respectively. The kinetic study revealed that they are noncompetitive inhibitors toward α-glucosidase. Also, fluorescence quenching was used to investigate the interaction of three inhibitors 7a, 7d, and 7h, with α-glucosidase. Accordingly, the binding constants, the number of binding sites, and values of thermodynamic parameters were determined for the interaction of candidate compounds toward the enzyme. Finally, the in silico cavity detection plus molecular docking was performed to find the allosteric site and key interactions between synthesized compounds and the target enzyme.
本文设计、合成并筛选了各种 N'-取代的苯亚甲基苯甲酰肼-1,2,3-三唑类化合物，以评估它们对α-葡萄糖苷酶的抑制活性。衍生物的结构通过氢谱和碳谱、傅里叶变换红外光谱、质谱和元素分析得到确认。与阳性对照阿卡波糖（IC = 752.10 µM）相比，所有衍生物均表现出良好的抑制活性，IC 值范围为 0.01 至 648.90 µM。其中，化合物 7a 和 7h 的抑制活性较强，IC 值分别为 0.02 和 0.01 µM。动力学研究表明，它们是非竞争性的α-葡萄糖苷酶抑制剂。此外，还利用荧光猝灭法研究了三种抑制剂 7a、7d 和 7h 与α-葡萄糖苷酶的相互作用。根据研究结果，确定了候选化合物与酶相互作用的结合常数、结合位点数和热力学参数值。最后，进行了计算腔检测加分子对接，以寻找合成化合物与靶酶之间的别构结合位点和关键相互作用。
