Novel (+)-usnic acid derivatives, computational studies and biological evaluation as neuroprotective agents.

IF 3.3 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2026-06-01 Epub Date: 2026-05-26 DOI:10.1080/17568919.2026.2675872

Gautam Kumar, Rahul Kumar, Tanish, Shashi Bala Singh

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引用次数: 0

Abstract

Aims: This study involves the semi-synthetic modification of (+)-usnic acid and the evaluation of the synthesized compounds for neuroprotective effects in scopolamine-injured C6 glial cells.

Materials and methods: Usnic acid derivatives were synthesized and characterized using ¹H and ¹³C nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Furthermore, compounds were evaluated for their neuroprotective effects using several biochemical assays, including acetylcholinesterase, lipid peroxidation, nitric oxide (NO), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSH/GSSG, reactive oxygen species (ROS), NFkB-p65, proinflammatory cytokines, and mitochondrial membrane potential (MMP). In silico studies were conducted to predict drug-likeness and binding sites for these molecules.

Results: (+)-Usnic acid, compounds 6, 13, and 16 showed antioxidative effects by decreasing ROS, malondialdehyde, and NO production in scopolamine-injured C6 glial cells. Additionally, these compounds enhanced the antioxidant effects by restoring the GSH/GSSG ratio and improving mitochondrial function by restoring the MMP in scopolamine-injured C6 glial cells. Moreover, these compounds exhibited anti-inflammatory effects by reducing IL-6 and tumor necrosis factor alpha (TNF-α) secretion and NFkB activity in C6 glial cells. In silico studies confirmed that these compounds decreased NO production by binding to neuronal nitric oxide synthase.

Conclusion: Usnic acid and its derivatives, 6, 13, and 16, increased the survival of scopolamine-injured C6 glial cells.

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新型(+)-usnic酸衍生物，作为神经保护剂的计算研究和生物学评价。

目的：研究(+)-usnic酸的半合成修饰，并评价合成的化合物对东莨菪碱损伤的C6神经胶质细胞的保护作用。材料与方法：合成了Usnic酸衍生物，并利用1H和13C核磁共振（NMR）和高分辨率质谱（HRMS）对其进行了表征。此外，通过多种生化分析，包括乙酰胆碱酯酶、脂质过氧化、一氧化氮（NO）、还原性谷胱甘肽（GSH）、氧化谷胱甘肽（GSSG）和GSH/GSSG、活性氧（ROS）、NFkB-p65、促炎细胞因子和线粒体膜电位（MMP），评估了化合物的神经保护作用。通过计算机研究预测了这些分子的药物相似性和结合位点。结果：(+)-Usnic酸、化合物6、13和16通过降低东莨菪碱损伤的C6胶质细胞中ROS、丙二醛和NO的产生而具有抗氧化作用。此外，这些化合物通过恢复GSH/GSSG比率增强抗氧化作用，并通过恢复东莨菪碱损伤的C6胶质细胞的MMP改善线粒体功能。此外，这些化合物通过降低C6胶质细胞中IL-6和肿瘤坏死因子α (TNF-α)的分泌以及NFkB活性而具有抗炎作用。硅研究证实，这些化合物通过结合神经元一氧化氮合酶减少一氧化氮的产生。结论：Usnic酸及其衍生物6、13、16可提高东莨菪碱损伤C6胶质细胞的存活率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.