α-Glucosidase plays a major role in degradation of carbohydrates to glucose. Therefore, inhibition of this enzyme can be useful in the treatment of carbohydrate-related diseases such as diabetes, cancer, and viral infections. In this study, a new series of acridine-9-carboxamide linked to 1,2,3-triazole-N-phenylacetamide derivatives 5a–m were designed, synthesized, and evaluated as potent α-glucosidase inhibitors. All the synthesized compounds showed excellent to good inhibitory activity against α-glucosidase with IC₅₀ values of 80.3 ± 0.9–564.3 ± 7.2 µM in comparison with standard drug acarbose (IC₅₀ value = 750.0 ± 10.5 μM). Among the synthesized compounds, the most active compound was 3-bromo derivative 5h with inhibitory activity around 9.3 times more than acarbose. this compound was selected for farther biological evaluations. Kinetic study of compound 5h revealed that it is a competitive inhibitor against α-glucosidase. Docking study of compound 5h and its regioisomer 5i with 4-bromo substituent were also carried out in the active site of α-glucosidase to gain an insight into the interaction modes of the synthesized compounds and rationalized structure–activity relationship between these two compounds. Compound 5h was also evaluated against α-amylase and no activity was observed in comparison with acarbose. Furthermore, in vitro cytotoxic assay of compound 5h against human normal and cancer cell lines HDF and MCF-7, respectively, revealed that this compound is a noncytotoxic agent. In silico pharmacokinetic and toxicity assays of compound 5h was performed and obtained results were compared with acarbose.

中文翻译：

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与1,2,3-三唑-N-苯基乙酰胺衍生物作为有效的α-葡萄糖苷酶抑制剂连接的新型a啶9-甲酰胺：设计，合成，体外和计算机生物学评估

α-葡萄糖苷酶在碳水化合物降解为葡萄糖方面起主要作用。因此，抑制该酶可用于治疗与碳水化合物有关的疾病，例如糖尿病，癌症和病毒感染。在这项研究中，设计，合成并评估了与1,2,3-三唑-N-苯基乙酰胺衍生物5a–m连接的一系列series啶-9-羧酰胺，并将其评估为有效的α-葡萄糖苷酶抑制剂。与标准药物阿卡波糖相比，所有合成的化合物均表现出优异的抗α-葡萄糖苷酶抑制活性，IC ₅₀值为80.3±0.9–564.3±7.2 µM（IC ₅₀值为750.0±10.5μM）。在合成的化合物中，活性最高的化合物是3-溴衍生物5h具有比阿卡波糖高9.3倍的抑制活性。选择该化合物进行进一步的生物学评估。化合物5h的动力学研究表明，它是抗α-葡萄糖苷酶的竞争性抑制剂。还在α-葡萄糖苷酶的活性位点对化合物5h及其具有4-溴取代基的区域异构体5i进行了对接研究，以了解合成化合物的相互作用模式以及这两种化合物之间合理的结构-活性关系。还评估了化合物5h对抗α-淀粉酶的作用，与阿卡波糖相比未观察到活性。此外，化合物5h的体外细胞毒性测定分别针对人类正常细胞系和癌细胞系HDF和MCF-7的化合物显示该化合物是非细胞毒性剂。在计算机上进行化合物5h的药代动力学和毒性测定，并将所得结果与阿卡波糖进行比较。