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 ana...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 59.9μM and thus elevated the LDLR level.Further molecular docking studies demonstrated that 4 and PCSK9 could form stable interactions via key hydrogen bonds.展开更多
基金supported by National Key R&D Program of China(2022YFF1100301)Major Science and Technology Project of Henan Province(231100310200)+1 种基金Yunnan Applied Basic Research Projects(202301AS070057)Yunnan Science and Technology Department(202305AH340005),DR PLANT.
文摘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 59.9μM and thus elevated the LDLR level.Further molecular docking studies demonstrated that 4 and PCSK9 could form stable interactions via key hydrogen bonds.
