Stereochemical assignment of clerodane-type diterpenes from the fruits of Casearia grewiifolia and their ability to inhibit PCSK9 expression
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초록

More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1–9 and 12–14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay. Among the undescribed compounds, the stereochemistry of two diastereomeric grewiifolins A and B (1 and 2) were extensively elucidated using 2D Nuclear Overhauser Effect Spectroscopy (NOESY) experiments, excitation-sculptured indirect detection experiments (EXSIDE), interproton distance analyses, and computational calculations that included quantum chemical shift calculations combined with DP4+ analysis. All isolates were assessed for their inhibitory activity against PCSK9 and IDOL mRNA expression. Among the compounds tested, compound 3 inhibited PCSK9 and IDOL mRNA expression. © 2023 Elsevier Ltd

키워드

Casearia grewiifoliaClerodane diterpenesEXSIDEIDOLInterproton distancePCSK9SalicaceaeLEAVESTWIGSBARKBINDINGIDOL
제목
Stereochemical assignment of clerodane-type diterpenes from the fruits of Casearia grewiifolia and their ability to inhibit PCSK9 expression
저자
Nhoek, PisethAn, Chae-YeongSon, Min-GyungChae, Hee-SungPel, PiseyKim, Young-MiKhiev, PisethChoi, Won JunChoi, Young HeeChin, Young-Won
DOI
10.1016/j.phytochem.2023.113864
발행일
2023-12
유형
Article
저널명
Phytochemistry
216
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1 ~ 13