PDF(Pubmed)
Abstract：
This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-one derivatives 5a-5o. The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a \"click chemistry\" approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including 1H NMR, 13C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of -9.9 and -9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski\'s criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development.
摘要：
这项研究的重点是合成一系列新的异恶唑啉基-1,2,3-三唑基-[1,4]-苯并恶嗪-3-酮衍生物5a-5o。该合成方法涉及遵循“点击化学”方法的双1,3-偶极环加成反应，从各自的[1,4]-苯并恶嗪-3-酮开始。此外,该研究旨在通过计算机模拟方法评估这些新合成化合物的抗糖尿病潜力。这种合成方法允许三种杂环组分的组合：[1,4]-苯并恶嗪-3-酮，1,2,3-三唑,和异恶唑啉，以其多样化的生物活动而闻名。合成过程包括两步过程。首先,进行1,3-偶极环加成反应，涉及与[1,4]-苯并恶嗪-3-酮连接的炔丙基部分和烯丙基叠氮化物。其次,使用来自第一步骤的产物进行第二环加成反应,含有烯丙基部分和肟。使用光谱法对合成的化合物进行了彻底的表征，包括1HNMR，13CNMR,DEPT-135和IR。这种分子对接方法揭示了合成化合物的有希望的抗糖尿病潜力，特别是针对两种关键的糖尿病相关酶：胰腺α-淀粉酶，两个合成分子5a和5o显示出9.2和9.1千卡/摩尔的最高亲和力值，分别,和肠道α-葡萄糖苷酶，两个合成分子5n和5e显示最高亲和力值-9.9和-9.6kcal/mol，分别。的确,合成的化合物已显示出作为抗糖尿病药物的巨大潜力，如针对α-淀粉酶和α-葡萄糖苷酶的分子对接研究所示。此外,ADME分析显示，在我们的研究中检查的所有合成化合物都显示出高的肠道吸收，符合Lipinski的标准,并且落在口服生物利用度所需的范围内，表明它们对口服药物开发的潜在适用性。
