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

doi:10.1007/s13659-024-00479-3

Natural Products and Bioprospecting ›› 2024, Vol. 14 ›› Issue (6): 57-57.DOI: 10.1007/s13659-024-00479-3

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

Yinling Wei^1,2, Hongyan Wen¹, Lian Yang¹, Bodou Zhang^1,2, Xiaoyu Li^1,2, 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

Received:2024-04-17 Online:2024-12-13 Published:2024-12-24
Contact: Yu Zhang,E-mail:zhangyu@mail.kib.ac.cn
Supported by:
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.

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

Yinling Wei^1,2, Hongyan Wen¹, Lian Yang¹, Bodou Zhang^1,2, Xiaoyu Li^1,2, 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

通讯作者: Yu Zhang,E-mail:zhangyu@mail.kib.ac.cn
基金资助:
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.

Abstract

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 K_D 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.

Key words: Hypecoum erectum L., Isoquinoline alkaloids, Hypecotumines A-D, PCSK9 inhibition

摘要： 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 K_D 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.

关键词: Hypecoum erectum L., Isoquinoline alkaloids, Hypecotumines A-D, PCSK9 inhibition

Yinling Wei, Hongyan Wen, Lian Yang, Bodou Zhang, Xiaoyu Li, Sheng Li, Jing Dong, Zhenzhen Liang, Yu Zhang. Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.[J]. Natural Products and Bioprospecting, 2024, 14(6): 57-57.

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

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

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