Abstract

Fourteen novel 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a–n were synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1H-imidazole and various benzyl azides. The synthesized compounds 8a–n were evaluated against yeast α-glucosidase, and all these compounds exhibited excellent inhibitory activity (IC₅₀ values in the range of 85.6 ± 0.4–231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC₅₀ = 750.0 μM). Among them, 4,5-diphenyl-imidazol-1,2,3-triazoles possessing 2-chloro and 2-bromo-benzyl moieties (compounds 8g and 8i) demonstrated the most potent inhibitory activities toward α-glucosidase. The kinetic study of the compound 8g revealed that this compound inhibited α-glucosidase in a competitive mode. Furthermore, docking calculations of these compounds were performed to predict the interaction mode of the synthesized compounds in the active site of α-glucosidase.

Graphic abstract

A novel series of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a–n was synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1Himidazole and various benzyl azides. The synthesized compounds 8a–n were evaluated against yeast α-glucosidase and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0.4-231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC50 = 750.0 μM).

中文翻译：

---

4,5-二苯基-咪唑-1,2,3-三唑杂化物作为新型抗糖尿病药物的设计和合成：体外α-葡萄糖苷酶抑制、动力学和对接研究

摘要

十四新颖4,5-二苯基咪唑1,2,3-三唑杂种8A - ñ用良好的收率由4,5-二苯基-2-（丙-2-炔-1-基硫基之间执行点击反应合成)-1H-咪唑和各种苄基叠氮化物。合成的化合物8a - n对酵母 α-葡萄糖苷酶进行了评估，所有这些化合物都表现出优异的抑制活性（IC ₅₀值在 85.6 ± 0.4–231.4 ± 1.0 μM 范围内），甚至比标准药物阿卡波糖（IC ₅₀  = 750.0 μM）。其中，具有2-氯和2-溴-苄基部分的4,5-二苯基-咪唑-1,2,3-三唑（化合物8g和8i）) 显示出对 α-葡萄糖苷酶最有效的抑制活性。化合物8g的动力学研究表明，该化合物以竞争模式抑制 α-葡萄糖苷酶。此外，对这些化合物进行对接计算以预测合成化合物在α-葡萄糖苷酶活性位点的相互作用模式。

图形摘要

一种新颖的一系列4,5-二苯基咪唑1,2,3-三唑杂种8A - Ñ由4,5-二苯基-2-（丙-2-炔-1-之间执行点击反应以良好的收率合成-ylthio)-1Himidazole 和各种苄基叠氮化物。合成的化合物8a - n对酵母 α-葡萄糖苷酶进行了评估，所有这些化合物都表现出优异的抑制活性（IC50 值范围为 85.6 ± 0.4-231.4 ± 1.0 μM），甚至比标准药物阿卡波糖（IC50 = 750.0）更有效微米）。