| ORIGINAL ARTICLES |
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Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L. |
| Yinling Wei1,2, Hongyan Wen1, Lian Yang1, Bodou Zhang1,2, Xiaoyu Li1,2, Sheng Li1, Jing Dong1, Zhenzhen Liang1, Yu Zhang1 |
1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
2. University of Chinese Academy of Sciences, Beijing 100049, China |
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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 1-4 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.
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| Keywords
Hypecoum erectum L.
Isoquinoline alkaloids
Hypecotumines A-D
PCSK9 inhibition
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| Fund:This work was financially supported by National Key R&D Program of China (2022YFF1100301), Major Science and Technology Project of Henan Province (231100310200), Yunnan Applied Basic Research Projects (202301AS070057), Yunnan Science and Technology Department (202305AH340005), and DR PLANT. |
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Corresponding Authors:
Yu Zhang,E-mail:zhangyu@mail.kib.ac.cn
E-mail: zhangyu@mail.kib.ac.cn
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Issue Date: 13 December 2024
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