In our work, several 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors (α-GIs) were synthesized and characterized by ¹H NMR, ¹³C NMR, and HRMS spectrum. Then, their bio-activity against the α-glucosidase (α-Glu) was further evaluated. Among them, almost all compounds displayed better bio-activity with IC₅₀ from 31.23 ± 0.89 to 213.50 ± 4.19 μM than acarbose (IC₅₀ = 700.20 ± 10.55 μM). In particular, compound 5o showed the best potency to inhibit α-Glu in a mixed manner. Moreover, the action mechanisms of 5o were further clarified including fluorescence quenching, circular dichroism spectra, three-dimensional fluorescence spectra, molecular docking, etc. All mechanism studies revealed that 5o could arouse the changed secondary structure of α-Glu to hinder enzyme catalytic activity. It was observed from an in vivo study that 5o of 20 mg/kg could significantly decrease by 24.45 % postprandial blood glucose in mice vs. the control. Meanwhile, 5o had low drug-drug interaction potential and was likely to be an orally active compound. Moreover, 5o was observed to be no obvious cytotoxicity to HEK-293 cells. In summary, compound 5o exhibited one potential to be further applied as an antidiabetic drug.

在我们的工作中，合成了几种作为 α-葡萄糖苷酶抑制剂 (α-GI) 的7H -[1,2,4]三唑并[3,4-b][1,3,4]噻二嗪-苯腙衍生物，并通过¹ H进行表征。 NMR、¹³ C NMR 和 HRMS 谱。然后，进一步评估了它们针对α-葡萄糖苷酶（α-Glu）的生物活性。其中，几乎所有化合物都表现出比阿卡波糖更好的生物活性，IC ₅₀为 31.23 ± 0.89 至 213.50 ± 4.19 μM（IC ₅₀  = 700.20 ± 10.55 μM）。特别是，化合物5o显示出以混合方式抑制 α-Glu 的最佳效力。此外，进一步阐明了5o的作用机制，包括荧光猝灭、圆二色光谱、三维荧光光谱、分子对接等。所有机制研究均表明5o可以引起α-Glu二级结构的改变，阻碍酶的催化活性。 。体内研究发现， 5o 20 mg/kg 可使小鼠餐后血糖较对照组显着降低 24.45%。同时，5o具有较低的药物相互作用潜力，并且可能是一种口服活性化合物。而且，观察到5o对HEK-293细胞没有明显的细胞毒性。总之，化合物5o表现出进一步作为抗糖尿病药物应用的潜力。