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

Piseth Nhoek, Chae Yeong An, Min Gyung Son, Hee Sung Chae, Pisey Pel, Young Mi Kim, Piseth Khiev, Won Jun Choi, Young Hee Choi, Young Won Chin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article number113864
JournalPhytochemistry
Volume216
DOIs
StatePublished - Dec 2023

Keywords

  • Casearia grewiifolia
  • Clerodane diterpenes
  • EXSIDE
  • IDOL
  • Interproton distance
  • PCSK9
  • Salicaceae

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