UPLC-PDA-QTOFMS-guided isolation of prenylated xanthones and benzoylphloroglucinols from the leaves of Garcinia oblongifolia and their migration-inhibitory activity

Sci Rep. 2016 Oct 21:6:35789. doi: 10.1038/srep35789.

Abstract

A UPLC-PDA-QTOFMS-guided isolation strategy was employed to screen and track potentially new compounds from Garcinia oblongifolia. As a result, two new prenylated xanthones, oblongixanthones D and E (1-2), six new prenylated benzoylphloroglucinol derivatives, oblongifolins V-Z (3-7) and oblongifolin AA (8), as well as a known compound oblongifolin L (9), were isolated from the EtOAc-soluble fraction of an acetone extract of the leaves of Garcinia oblongifolia guided by UPLC-PDA-QTOFMS analysis. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analysis and mass spectrometry. Experimental and calculated ECD spectra were used to determine the absolute configurations. The results of wound healing and transwell migration assay showed that oblongixanthones D (1), E (2), and oblongifolin L (9) have the ability to inhibit cancer cell migration in lower cytotoxic concentrations. Western blotting results showed that these compounds exhibited an anti-metastasis effect mainly through downregulating RAF protein levels. In addition, 2 and 9 could inhibit phospho-MEK and phospho-ERK at downstream. Moreover, 1, 2, and 9 could inhibit snail protein level, suggesting that they could regulate the EMT pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Line, Tumor
  • Cell Migration Inhibition / drug effects*
  • Chromatography, High Pressure Liquid
  • Drug Screening Assays, Antitumor
  • Epithelial-Mesenchymal Transition / drug effects
  • Garcinia / chemistry*
  • Hep G2 Cells
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / chemistry
  • Phloroglucinol / isolation & purification
  • Plant Leaves / chemistry
  • Prenylation
  • Spectrometry, Mass, Electrospray Ionization
  • Xanthones / chemistry
  • Xanthones / isolation & purification*
  • Xanthones / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Xanthones
  • Phloroglucinol