Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310006, China.
Zhejiang Key Laboratory of Pollution Exposure and Health Intervention, Interdisciplinary Research Academy, Zhejiang Shuren University, Hangzhou 310015, China.
Biomolecules. 2023 Mar 27;13(4):600. doi: 10.3390/biom13040600.
Alzheimer's disease (AD) is a typical progressive neurodegenerative disorder, and with multiple possible pathogenesis. Among them, coumarin derivatives could be used as potential drugs as monoamine oxidase-B (MAO-B) inhibitors. Our lab has designed and synthesized coumarin derivatives based on MAO-B. In this study, we used nuclear magnetic resonance (NMR)-based metabolomics to accelerate the pharmacodynamic evaluation of candidate drugs for coumarin derivative research and development. We detailed alterations in the metabolic profiles of nerve cells with various coumarin derivatives. In total, we identified 58 metabolites and calculated their relative concentrations in U251 cells. In the meantime, the outcomes of multivariate statistical analysis showed that when twelve coumarin compounds were treated with U251cells, the metabolic phenotypes were distinct. In the treatment of different coumarin derivatives, there several metabolic pathways changed, including aminoacyl-tRNA biosynthesis, D-glutamine and D-glutamate metabolism, glycine, serine and threonine metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glutathione metabolism and valine, leucine and isoleucine biosynthesis. Our work documented how our coumarin derivatives affected the metabolic phenotype of nerve cells in vitro. We believe that these NMR-based metabolomics might accelerate the process of drug research in vitro and in vivo.
阿尔茨海默病（AD）是一种典型的进行性神经退行性疾病，具有多种可能的发病机制。其中，香豆素衍生物可以作为单胺氧化酶-B（MAO-B）抑制剂的潜在药物。我们实验室基于 MAO-B 设计并合成了香豆素衍生物。在这项研究中，我们使用基于核磁共振（NMR）的代谢组学来加速候选药物的药效评估，以用于香豆素衍生物的研发。我们详细描述了各种香豆素衍生物对神经细胞代谢谱的改变。总共鉴定出 58 种代谢物，并计算了它们在 U251 细胞中的相对浓度。同时，多元统计分析的结果表明，当用十二种香豆素化合物处理 U251 细胞时，代谢表型明显不同。在不同香豆素衍生物的治疗中，有几个代谢途径发生了变化，包括氨酰-tRNA 生物合成、D-谷氨酰胺和 D-谷氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢、牛磺酸和次牛磺酸代谢、精氨酸生物合成、丙氨酸、天冬氨酸和谷氨酸代谢、苯丙氨酸、酪氨酸和色氨酸生物合成、谷胱甘肽代谢和缬氨酸、亮氨酸和异亮氨酸生物合成。我们的工作记录了我们的香豆素衍生物如何影响神经细胞的代谢表型在体外。我们相信，这些基于 NMR 的代谢组学可能会加速药物在体外和体内的研究进程。
