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海胆甾醇,一种新型细胞毒芳香酶抑制剂麦角甾醇衍生物,来自红海海草。

Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass .

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.

出版信息

Mar Drugs. 2020 Jul 8;18(7):354. doi: 10.3390/md18070354.

DOI:10.3390/md18070354
PMID:32650455
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7401251/
Abstract

(Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol () was isolated from the methanolic extract of growing in the Red Sea, along with two known first-reported sterols, namely ergosterol () and stigmasterol (), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.

摘要

(Forssk.) Den Hartog 是一种属于水鳖科的海草,具有广泛存在的植物化学成分和重要的药理学潜力,包括抗氧化、抗病毒和细胞毒性活性。在这项工作中,从生长在红海的中分离到一种新的麦角甾醇衍生物,命名为塔拉萨甾醇(),以及两种已知的首次报道的甾醇,即麦角甾醇()和豆甾醇(),使用了不同的色谱技术。根据 1D 和 2D NMR 光谱和高分辨率质谱(HR-MS)以及与文献数据的比较,确定了新化合物的结构。新的麦角甾醇衍生物对人宫颈癌(HeLa)和人乳腺癌(MCF-7)细胞系表现出显著的体外抗增殖活性,IC 值分别为 8.12 和 14.24 µM。此外,对新甾体的对接研究解释了与芳香酶酶的可能结合相互作用;这种抑制在宫颈癌和乳腺癌的治疗中都是有益的。使用液相色谱结合高分辨率电喷雾电离质谱(LC-ESI-HR-MS)对粗提取物进行代谢分析,揭示了存在一系列酚类化合物、甾醇和神经酰胺,以及二酯和三酯。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/d95970b50eec/marinedrugs-18-00354-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/f61bc088839b/marinedrugs-18-00354-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/15f333489754/marinedrugs-18-00354-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/be81ec62963b/marinedrugs-18-00354-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/f27d2796ac56/marinedrugs-18-00354-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/10db6a6bf60d/marinedrugs-18-00354-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/d95970b50eec/marinedrugs-18-00354-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/f61bc088839b/marinedrugs-18-00354-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/15f333489754/marinedrugs-18-00354-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/be81ec62963b/marinedrugs-18-00354-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/f27d2796ac56/marinedrugs-18-00354-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/10db6a6bf60d/marinedrugs-18-00354-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4446/7401251/d95970b50eec/marinedrugs-18-00354-g006.jpg

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