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具有辅助β-咔啉眼镜潜力的基于色氨酸的生物活性铜配合物对人乳腺癌细胞的作用:体外和体内研究。

Bioactive Tryptophan-Based Copper Complex with Auxiliary β-Carboline Spectacle Potential on Human Breast Cancer Cells: In Vitro and In Vivo Studies.

机构信息

Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 62529, Saudi Arabia.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

出版信息

Molecules. 2021 Mar 14;26(6):1606. doi: 10.3390/molecules26061606.

Abstract

Biocompatible tryptophan-derived copper () and zinc () complexes with norharmane (β-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes and were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of against MCF7 cells with an IC value of 7.8 ± 0.4 μM compared to (less active, IC ~ 20 μM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of .

摘要

设计、合成、表征了具有 norharmane(β-咔啉)的生物相容色氨酸衍生的铜()和锌()配合物,并评估了它们在体外和体内的潜在抗癌活性。两种配合物[Cu(trp)(nor)]()和[Zn(trp)(nor)]()的体外细胞毒性均针对两种癌细胞(人乳腺癌)MCF7 和(肝肝癌)HepG2 细胞与非致瘤细胞(人胚肾)HEK293 细胞进行了评估。结果显示,[Cu(trp)(nor)]()对 MCF7 细胞具有潜在的良好选择性,IC 值为 7.8 ± 0.4 μM,而[Zn(trp)(nor)](活性较低,IC~20 μM)。此外,我们分析了谷胱甘肽水平、脂质过氧化和可视化 ROS 生成,以深入了解其机制途径并见证氧化应激。这些体外结果通过体内实验得到了证实,这也支持了自由基介导的氧化应激。彗星试验证实了导致 DNA 损伤的氧化应激。肝组织病理学也证实了 的低毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a47/8001361/77e326c997cd/molecules-26-01606-g001.jpg

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