Cytotoxic Rocaglate Derivatives from Leaves of Aglaia perviridis

Sci Rep. 2016 Jan 28:6:20045. doi: 10.1038/srep20045.

Abstract

Rocaglates are a series of structurally complex secondary metabolites with considerable cytotoxicity that have been isolated from plants of the Aglaia genus (Meliaceae). A new rocaglate (aglapervirisin A, 1) and its eight new biosynthetic precursors of rocaglate (aglapervirisins B-J, 2-9) together with five known compounds, were isolated from the leaves of Aglaia perviridis. Their structures were elucidated based on a joint effort of spectroscopic methods [IR, UV, MS, ECD, 1D- and 2D-NMR, HRESIMS], chemical conversion and single-crystal X-ray diffraction. Among these isolates, three (1, 10-11) were silvestrols, a rare subtype rocaglates, exhibiting notable cytotoxicity against four human tumor cell lines, with IC50 values between 8.0 and 15.0 nM. Aglapervirisin A (1) induces cell cycle arrest at the G2/M-phase boundary at concentration 10 nM accompanied by reductions in the expression levels of Cdc2 and Cdc25C in HepG2 cells after 72h co-incubation, and further induces the apoptosis of HepG2 cells at concentrations over 160 nM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aglaia / chemistry*
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Hep G2 Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts