作为帕金森病自由基清除剂的亚苄基 2-氯喹啉衍生物的体内、合成、表征和体外研究

IF 1.7 Q3 PHARMACOLOGY & PHARMACY Drug Research Pub Date : 2024-02-01 Epub Date: 2024-02-12 DOI:10.1055/a-2231-1311
Gomathy Subramanian, Kaveri Prasad, Jagdish Chand, Thiyyar K Amarjith, Antony A Shanish
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引用次数: 0

摘要

帕金森病是大脑黑质部分多巴胺能神经元的丧失导致的神经变性。而活性氧和线粒体损伤被认为是神经变性的主要病理生理机制。我们合成了亚苄基 2-氯喹啉衍生物,并通过傅立叶变换红外光谱、核磁共振和质谱分析对其进行了表征。通过 MTT 法、DPPH 法和谷胱甘肽测量法对 SHSY5Y 神经母细胞瘤细胞系进行体外细胞毒性检测,进一步评估了所设计的化合物。研究发现,化合物 JD-7 和 JD-4 的结合亲和力分别为 - 7.941 和 - 7.633 kcal/mol,MMGBSA 得分为 - 64.614 和 - 62.817 kcal/mol。通过 MTT 法,在 125 µg/mL 的最小剂量下,化合物 JD-7 的细胞存活率最高,达到 87.64%。在浓度从 0 到 125、250 和 500 微克/毫升不断增加的过程中,观察到了神经毒性效应。此外,在 125 µg/mL 的最低浓度下,JD-7 的自由基清除活性为 36.55。在 125 µg/mL 浓度下,发现在鱼藤酮处理中 GSH % 和 GSSG % 有所增加,而在预先处理过鱼藤酮的 SHSY5Y 神经母细胞瘤细胞系中,发现 JD-7 和 JD-4 会降低谷胱甘肽水平。在合成的亚苄基氯喹啉衍生物 JD-1 至 JD-13 中,发现化合物 JD-7 和 JD-4 在 SHSY5Y 神经母细胞瘤细胞系中的细胞存活率、自由基清除分子和谷胱甘肽水平最高,可用作帕金森病的自由基清除剂。
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In-silico, Synthesis, Characterization, and In-vitro Studies on Benzylidene-based 2-chloroquinolin Derivatives as Free Radical Scavengers in Parkinson's Disease.

Parkinson's disease is the loss of dopaminergic neurons in the substantial nigra part of the brain leading to neurodegeneration. Whereas, reactive oxygen species and mitochondrial impairment are considered to be the major pathophysiology of neurodegeneration. The benzylidene-based 2-chloroquinolin derivatives were synthesized and characterized by FT-IR, NMR, and MS spectrometry which were screened using various in-silico approaches. The designed compounds were further assessed using in-vitro cytotoxicity assay by the MTT method, DPPH assay, and Glutathione measurements in the SHSY5Y neuroblastoma cell lines. The compounds JD-7 and JD-4 were found to have a binding affinity of - 7.941 and - 7.633 kcal/mol with an MMGBSA score of - 64.614 and - 62.817 kcal/mol. The compound JD-7 showed the highest % Cell viability of 87.64% at a minimal dose of 125 µg/mL by the MTT method. The neurotoxicity effects were observed at increasing concentrations from 0 to 125, 250, and 500 µg/mL. Further, free radical scavenging activity for the JD-7 was found to be 36.55 at lowest 125 µg/mL concentrations. At 125 µg/mL, GSH % and GSSG % were found to be increasing in rotenone treatment, whereas JD-7 and JD-4 were found in the downregulation of glutathione level in the pre-treated rotenone SHSY5Y neuroblastoma cell lines. The benzylidene-based chloroquinolin derivatives were synthesized, and among the compounds JD-1 to JD-13, the compounds JD-7, and JD-4 were found to have having highest % cell viability, free radical scavenging molecules, and glutathione levels in the SHSY5Y neuroblastoma cell lines and could be used as free radical scavengers in Parkinson's disease.

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来源期刊
Drug Research
Drug Research PHARMACOLOGY & PHARMACY-
CiteScore
3.50
自引率
0.00%
发文量
67
期刊介绍: Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.
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