Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.

IF 4.8 3区 化学 Q1 CHEMISTRY, MEDICINAL Natural Products and Bioprospecting Pub Date : 2024-10-15 DOI:10.1007/s13659-024-00479-3
Yinling Wei, Hongyan Wen, Lian Yang, Bodou Zhang, Xiaoyu Li, Sheng Li, Jing Dong, Zhenzhen Liang, Yu Zhang
{"title":"Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.","authors":"Yinling Wei,&nbsp;Hongyan Wen,&nbsp;Lian Yang,&nbsp;Bodou Zhang,&nbsp;Xiaoyu Li,&nbsp;Sheng Li,&nbsp;Jing Dong,&nbsp;Zhenzhen Liang,&nbsp;Yu Zhang","doi":"10.1007/s13659-024-00479-3","DOIUrl":null,"url":null,"abstract":"<div><p>Four new isoquinoline alkaloids, hypecotumines A-D (<b>1–4</b>), were isolated and identified from the whole herbs of <i>Hypecoum erectum</i> L. Their structures were determined by a combination of HRESIMS, NMR, and X-ray diffraction analysis methods. Compounds <b>1</b>–<b>4</b> were characterized by a terminal double bond at C-9 and their plausible biosynthetic pathway was hypothesized. Since PCSK9 plays a key role in the development of cardiovascular disease (CVD), exploration of PCSK inhibitors from natural products are beneficial for drug discovery of CVD treatment. SPR and Western blot assays showed compound <b>4</b> had PCSK9 inhibition activity with K<sub>D</sub> value of 59.9 µM and thus elevated the LDLR level. Further molecular docking studies demonstrated that <b>4</b> and PCSK9 could form stable interactions via key hydrogen bonds.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s13659-024-00479-3.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Natural Products and Bioprospecting","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13659-024-00479-3","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Four new isoquinoline alkaloids, hypecotumines A-D (1–4), were isolated and identified from the whole herbs of Hypecoum erectum L. Their structures were determined by a combination of HRESIMS, NMR, and X-ray diffraction analysis methods. Compounds 14 were characterized by a terminal double bond at C-9 and their plausible biosynthetic pathway was hypothesized. Since PCSK9 plays a key role in the development of cardiovascular disease (CVD), exploration of PCSK inhibitors from natural products are beneficial for drug discovery of CVD treatment. SPR and Western blot assays showed compound 4 had PCSK9 inhibition activity with KD value of 59.9 µM and thus elevated the LDLR level. Further molecular docking studies demonstrated that 4 and PCSK9 could form stable interactions via key hydrogen bonds.

Graphical Abstract

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
具有潜在 PCSK9 抑制活性的新异喹啉生物碱 Hypecotumines A-D from Hypecoum erectum L.
结合 HRESIMS、核磁共振和 X 射线衍射分析方法确定了它们的结构。化合物 1-4 的特征是 C-9 上有一个末端双键,并假设了其合理的生物合成途径。由于 PCSK9 在心血管疾病(CVD)的发生发展中起着关键作用,因此从天然产物中探索 PCSK 抑制剂有利于发现治疗心血管疾病的药物。SPR 和 Western 印迹分析表明,化合物 4 具有 PCSK9 抑制活性,KD 值为 59.9 µM,从而提高了 LDLR 水平。进一步的分子对接研究表明,化合物 4 与 PCSK9 可通过关键氢键形成稳定的相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Natural Products and Bioprospecting
Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-
CiteScore
8.30
自引率
2.10%
发文量
39
审稿时长
13 weeks
期刊最新文献
Dayuan Yin alleviates symptoms of HCoV-229E-induced pneumonia and modulates the Ras/Raf1/MEK/ERK pathway Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L. Paeoniflorin mitigates insulin-like growth factor 1-induced lipogenesis and inflammation in human sebocytes by inhibiting the PI3K/Akt/FoxO1 and JAK2/STAT3 signaling pathways Expanding horizons of iminosugars as broad-spectrum anti-virals: mechanism, efficacy and novel developments Structure characterization and immunoactivity on dendritic cells of two neutral polysaccharides from Dictyophora rubrovalvata
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1