Type 2 diabetes is a chronic disease characterized by insulin resistance and alterations in incretin secretion, such as the glucagon-like peptide-1 (GLP-1) hormone. GLP-1 plays a crucial role in signaling insulin production in the pancreas, with its activity regulated by the dipeptidyl peptidase 4 (DPP-4) enzyme. DPP-4 presents an intriguing strategy for controlling type 2 diabetes. This study focuses on synthesizing 22 novel oxadiazolone and pyrimidinone derivatives, in vitro DPP-4 inhibition, and elucidating binding modes through molecular docking simulations. Nine compounds showed promising inhibitory activity, with IC₅₀ values ranging from 0.3 to 1.86 mM. Molecular docking simulations revealed interactions between these compounds and critical residues in the enzyme's active site, such as Arg125, Glu206, Ser630, and His740. This investigation introduces a new class of DPP-4 inhibitors, providing insights into the design of more potent molecules as potential candidates for combating type 2 diabetes. The findings contribute to developing innovative therapeutics for managing this prevalent metabolic disorder.

中文翻译：

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发现含有恶二唑酮或嘧啶酮核心的新型杂环衍生物作为 DPP-4 抑制剂


2 型糖尿病是一种慢性疾病，其特征是胰岛素抵抗和肠促胰岛素分泌改变，例如胰高血糖素样肽-1 (GLP-1) 激素。 GLP-1 在胰腺中胰岛素产生的信号传导中发挥着至关重要的作用，其活性受二肽基肽酶 4 (DPP-4) 酶的调节。 DPP-4 提出了一种控制 2 型糖尿病的有趣策略。本研究重点合成 22 种新型恶二唑酮和嘧啶酮衍生物，体外抑制 DPP-4，并通过分子对接模拟阐明结合模式。九种化合物显示出良好的抑制活性，IC ₅₀ 值范围为 0.3 至 1.86 mM。分子对接模拟揭示了这些化合物与酶活性位点中的关键残基（例如 Arg125、Glu206、Ser630 和 His740）之间的相互作用。这项研究引入了一类新的 DPP-4 抑制剂，为设计更有效的分子作为对抗 2 型糖尿病的潜在候选分子提供了见解。这些发现有助于开发创新疗法来治疗这种普遍的代谢紊乱。