Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.
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...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2024-10-01
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| Series: | Natural Products and Bioprospecting |
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| Online Access: | https://doi.org/10.1007/s13659-024-00479-3 |
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| author | Yinling Wei Hongyan Wen Lian Yang Bodou Zhang Xiaoyu Li Sheng Li Jing Dong Zhenzhen Liang Yu Zhang |
| author_facet | Yinling Wei Hongyan Wen Lian Yang Bodou Zhang Xiaoyu Li Sheng Li Jing Dong Zhenzhen Liang Yu Zhang |
| author_sort | Yinling Wei |
| collection | DOAJ |
| description | 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. Graphical Abstract |
| format | Article |
| id | doaj-art-b4102342e6824016ba5d9cc3600477ca |
| institution | OA Journals |
| issn | 2192-2195 2192-2209 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Natural Products and Bioprospecting |
| spelling | doaj-art-b4102342e6824016ba5d9cc3600477ca2025-08-20T02:17:46ZengSpringerOpenNatural Products and Bioprospecting2192-21952192-22092024-10-011411910.1007/s13659-024-00479-3Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.Yinling Wei0Hongyan Wen1Lian Yang2Bodou Zhang3Xiaoyu Li4Sheng Li5Jing Dong6Zhenzhen Liang7Yu Zhang8State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesState Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of SciencesAbstract 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. Graphical Abstracthttps://doi.org/10.1007/s13659-024-00479-3Hypecoum erectum L.Isoquinoline alkaloidsHypecotumines A-DPCSK9 inhibition |
| spellingShingle | 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. Natural Products and Bioprospecting Hypecoum erectum L. Isoquinoline alkaloids Hypecotumines A-D PCSK9 inhibition |
| title | Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L. |
| title_full | Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L. |
| title_fullStr | Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L. |
| title_full_unstemmed | Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L. |
| title_short | Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L. |
| title_sort | hypecotumines a d new isoquinoline alkaloids with potential pcsk9 inhibition activity from hypecoum erectum l |
| topic | Hypecoum erectum L. Isoquinoline alkaloids Hypecotumines A-D PCSK9 inhibition |
| url | https://doi.org/10.1007/s13659-024-00479-3 |
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