Chemical Components of the Fruits of Morus nigra Linn.: Methyl Caffeate as a Potential Anticancer Agent by Targeting 3-Phosphoglycerate Dehydrogenase,Journal of Agricultural and Food Chemistry

当前位置： X-MOL 学术 › J. Agric. Food Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Chemical Components of the Fruits of Morus nigra Linn.: Methyl Caffeate as a Potential Anticancer Agent by Targeting 3-Phosphoglycerate Dehydrogenase
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2021-10-19 , DOI: 10.1021/acs.jafc.1c03215
Yali Wang ₁ , Mengzhu Zheng ₂ , Qinghua Jiang ₃ , Yang Xu ₁ , Xuechen Zhou ₂ , Na Zhang ₁ , Dejuan Sun ₁ , Hua Li _{1,

2} , Lixia Chen ₁

Affiliation

Two previously undescribed compounds, moranigrine A (1) and morusamine (2), along with 18 known compounds were isolated from the fruits of Morus nigra Linn. and structurally characterized using spectroscopic data and electronic circular dichroism analyses. All isolates were evaluated for their inhibitory effects on the 3-phosphoglycerate dehydrogenase (PHGDH) enzyme, which catalyzes the first committed step for the synthesis of glucose-derived serine and is associated with many kinds of cancers. Among these compounds, methyl caffeate (3) exhibited effective inhibition against PHGDH and was directly bound to PHGDH based on the microscale thermophoresis method and the cellular thermal shift assay. Further biochemical assays revealed that 3 was a noncompetitive inhibitor with respect to the substrate of 3-phosphoglycerate and exhibited a concentration-dependent inhibition. Molecular docking demonstrated that 3 coordinated in an allosteric site of PHGDH with low binding energy. Meanwhile, 3 was selectively toxic to high PHGDH-expressing cancer cell lines and could cause apoptosis of cervical cancer cells in micromolar concentrations and could obviously inhibit tumor growth in the HeLa xenograft mouse model with low toxicities. Therefore, 3 could be developed as a potential inhibitor of PHGDH for the treatment of cancers. Our present study provides information about M. nigra as a functional food or pharmaceutical supplement in the application of cancer prevention and treatment.

中文翻译：

黑桑果的化学成分：咖啡酸甲酯作为靶向 3-磷酸甘油酸脱氢酶的潜在抗癌剂

从Morus nigra Linn的果实中分离出两种先前未描述的化合物，moranigrine A ( 1 ) 和 morusamine ( 2 )，以及 18 种已知化合物。并使用光谱数据和电子圆二色性分析进行结构表征。评估了所有分离物对 3-磷酸甘油酸脱氢酶 (PHGDH) 酶的抑制作用，该酶催化葡萄糖衍生丝氨酸合成的第一步，并与多种癌症有关。在这些化合物中，咖啡酸甲酯 ( 3) 表现出对 PHGDH 的有效抑制作用，并基于微尺度热泳法和细胞热位移测定直接与 PHGDH 结合。进一步的生化分析表明，3是一种对 3-磷酸甘油酸底物的非竞争性抑制剂，并表现出浓度依赖性抑制作用。分子对接表明3在PHGDH的变构位点以低结合能协调。同时，3对高表达PHGDH的癌细胞系有选择性毒性，在微摩尔浓度下可引起宫颈癌细胞凋亡，并能明显抑制HeLa异种移植小鼠模型中的肿瘤生长，且毒性低。因此，3可以开发为潜在的 PHGDH 抑制剂，用于治疗癌症。我们目前的研究提供了有关M. nigra作为功能性食品或药物补充剂在癌症预防和治疗中的应用的信息。

更新日期：2021-10-27

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11