In vitro alpha amylase and protein denaturation inhibitory activity of newer generation Schiff base Oxazolone derivatives: Synthesis, chemical characterization, molecular docking, MD simulation, DFT, ADMET, and bioactivity.
慢性炎症与糖尿病是密切相关的疾病，参与代谢功能障碍和疾病发病机制。因此，通过多步合成方法合成了三种新的噁唑酮席夫碱衍生物（JS1A、JS2A和JS3A），并通过FTIR、¹H NMR、¹³C NMR、质谱和元素分析进行了表征。通过计算与实验相结合的研究对一系列合成化合物进行了筛选，以评估其抗糖尿病和抗炎特性。与胰腺α-淀粉酶（4GQR）和环氧合酶-2（6COX）的分子对接研究显示良好的结合相互作用，其中JS2A对两个靶标均具有最高的对接亲和力。此外，100 ns的分子动力学模拟表明蛋白质-配体复合物是稳定的，尤其是JS2A。利用前沿分子轨道和分子静电势对合成的衍生物进行了分析，以确定合适的电子性质、反应位点和相互作用潜力。基于ADMET预测研究，类药性、药代动力学行为和较低的预测毒性被认为是可接受的；溶解性和渗透性可能需要改善。所有合成化合物在体外均以剂量依赖性方式显示出α-淀粉酶抑制活性和蛋白质变性抑制活性。在合成的化合物中，JS2A对α-淀粉酶和蛋白质变性表现出强的体外抑制活性。总体而言，这些结果表明席夫碱噁唑酮衍生物可作为具有潜在抗糖尿病和抗炎特性的多功能骨架。
Chronic inflammation and diabetes mellitus are closely linked diseases and involved in metabolic dysfunction and disease pathogenesis. So, three new Oxazolone Schiff base derivatives (JS1A, JS2A and JS3A) were synthesized by a multi-step procedure, and then characterized by FTIR, H NMR, C NMR, mass spectrometry and elemental analysis. A series of synthetic compounds was screened by integrated computational and experimental studies to assess their antidiabetic and anti-inflammatory properties. Molecular docking studies with pancreatic α-amylase (4GQR) and cyclooxygenase-2 (6COX) revealed good binding interactions with the highest docking affinity of JS2A with both targets. Furthermore, the 100 ns molecular dynamics simulations showed that the protein-ligand complexes were stable, especially for JS2A. The synthesized derivatives have been analyzed using frontier molecular orbital and molecular electrostatic potential to identify suitable electronic properties, reactive sites, and interaction potentials. The drug-likeness, pharmacokinetic behavior, and low predicted toxicity were deemed acceptable based on ADMET prediction studies; improvements in solubility and permeability may be needed. All synthesized compounds showed α-amylase inhibitory and protein-denaturation inhibitory activities in vitro in a dose-dependent manner. Among the synthesized compounds, JS2A showed strong in vitro inhibitory activities against α-amylase and protein denaturation. Overall, these results indicate that Schiff base Oxazolone derivatives can be considered as multifunctional scaffolds with prospective antidiabetic and anti-inflammatory properties.
Supriyo Saha, Jayant Sarawat, Lamiae Elbouamri, Samir Chtita. In vitro alpha amylase and protein denaturation inhibitory activity of newer generation Schiff base Oxazolone derivatives: Synthesis, chemical characterization, molecular docking, MD simulation, DFT, ADMET, and bioactivity.. Biochemical and biophysical research communications. 2026; doi:10.1016/j.bbrc.2026.154167.
Supriyo Saha, Jayant Sarawat, Lamiae Elbouamri, Samir Chtita (2026). In vitro alpha amylase and protein denaturation inhibitory activity of newer generation Schiff base Oxazolone derivatives: Synthesis, chemical characterization, molecular docking, MD simulation, DFT, ADMET, and bioactivity.. Biochemical and biophysical research communications. https://doi.org/10.1016/j.bbrc.2026.154167
Supriyo Saha, Jayant Sarawat, Lamiae Elbouamri, Samir Chtita. In vitro alpha amylase and protein denaturation inhibitory activity of newer generation Schiff base Oxazolone derivatives: Synthesis, chemical characterization, molecular docking, MD simulation, DFT, ADMET, and bioactivity.[J]. Biochemical and biophysical research communications, 2026 doi:10.1016/j.bbrc.2026.154167.
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