In this study, a new series of quinazolinone-1,2,3-triazole-acetamide hybrids 8a–m, using by molecular hybridization of the potent α-glucosidase inhibitor pharmacophores, was designed and evaluated against carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase. All the synthesized compounds with IC₅₀ values in the range of 45.3 ± 1.4 µM to 195.5 ± 4.7 µM were significantly more potent than standard inhibitor against α-glucosidase, while these compounds were not active against α-amylase in comparison to standard inhibitor. Representatively, compound 8a with IC₅₀ = 45.3 ± 1.4 µM was around 17 times more potent than standard inhibitor acarbose (IC₅₀ = 750.0 ± 12.5 µM). The inhibition kinetic analysis of the compound 8a indicated that this compound was a competitive α-glucosidase inhibitor. Molecular modeling analysis confirmed that the most potent inhibitors 8a and 8b well accommodated in the modeled α-glucosidase active site and it was also revealed that these compounds formed stable inhibitor–receptor complexes with the α-glucosidase in comparison to acarbose. In silico pharmacokinetic and toxicity of the most potent compounds were evaluated and obtained results were compared with acarbose. Furthermore, the most potent compounds were also evaluated against human normal cells and no cytotoxicity was observed.

在这项研究中，设计了一系列新的喹唑啉酮-1,2,3-三唑-乙酰胺杂化物8a–m，通过有效的α-葡萄糖苷酶抑制剂药效基团的分子杂交，设计并评估了其抗碳水化合物水解酶α-葡萄糖苷酶和α-淀粉酶。所有合成的IC ₅₀值在45.3±1.4 µM至195.5±4.7 µM范围内的化合物均比标准抑制剂对α-葡萄糖苷酶的抑制作用强得多，而与标准抑制剂相比，这些化合物对α-淀粉酶没有活性。代表性的是，化合物50a的IC ₅₀  = 45.3±1.4 µM，其效力是标准抑制剂阿卡波糖（IC ₅₀ = 17倍） = 750.0±12.5 µM）。化合物8a的抑制动力学分析表明该化合物是竞争性α-葡萄糖苷酶抑制剂。分子模型分析证实，最有效的抑制剂8a和8b很好地容纳在模拟的α-葡萄糖苷酶活性位点中，并且还表明与阿卡波糖相比，这些化合物与α-葡萄糖苷酶形成了稳定的抑制剂-受体复合物。在计算机上评估了最有效化合物的药代动力学和毒性，并将所得结果与阿卡波糖进行了比较。此外，还评估了针对人类正常细胞的最有效化合物，未观察到细胞毒性。