Aim: To enrich the pool of α-amylase inhibitors to manage Type 2 diabetes. Methods: Synthesis, conformational study, α-amylase inhibitory action and various in silico studies of novel N'-(arylbenzylidene)-2-(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-1-yl)acetohydrazides carried out. Results: Compound H6 demonstrated the highest activity (IC50 = 0.0437 μmol mL-1) among the tested compounds. Structure-activity relationship study suggested that variable substitution at the aryl ring has a pivotal role in determining the inhibitory action of tested compounds. Docking simulations of the most active compound (H6) confirmed its interaction potential with active site residues of A. oryzae α-amylase. The root-mean-square deviation fluctuations substantiated the stability of protein-ligand complex. Absorption, distribution, metabolism and excretion prediction revealed optimal values for absorption, distribution, metabolism and excretion parameters. Conclusion: The developed molecules could be beneficial for the development of novel α-amylase inhibitors to treat Type 2 diabetes.

中文翻译：

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α-淀粉酶抑制和新型萘并[2,3-d]咪唑-4,9-二酮连接的 N-酰基腙的计算机研究。

目的：丰富 α-淀粉酶抑制剂库以治疗 2 型糖尿病。方法：新型 N'-(芳基亚苄基)-2-(4,9-二氧代-4,9-二氢-1H-萘并[2,3-d]的合成、构象研究、α-淀粉酶抑制作用和各种计算机研究]咪唑-1-基)乙酰肼进行。结果：化合物 H6 在测试化合物中表现出最高的活性（IC50 = 0.0437 μmol mL-1）。结构-活性关系研究表明，芳环上的可变取代在确定测试化合物的抑制作用中起着关键作用。最活跃的化合物 (H6) 的对接模拟证实了其与米曲霉 α-淀粉酶活性位点残基的相互作用潜力。均方根偏差波动证实了蛋白质-配体复合物的稳定性。吸收、分布、代谢和排泄预测揭示了吸收、分布、代谢和排泄参数的最佳值。结论：所开发的分子可能有利于开发治疗 2 型糖尿病的新型 α-淀粉酶抑制剂。