Synthesis and biological evaluation of Oblongifolin C derivatives as c-Met inhibitors

Bioorg Med Chem. 2016 Sep 15;24(18):4120-4128. doi: 10.1016/j.bmc.2016.06.054. Epub 2016 Jun 27.

Abstract

Oblongifolin C, one of the polyprenylated benzoylphloroglucinol natural products (PPAPs) isolated from the fruits of Garcinia yunnanensis Hu, was recently discovered to be a potent anti-tumor agent. A collection of 12 derivatives with modifications on the benzophenone moieties were synthesized and tested for c-Met kinase inhibition and cytotoxicity against the HepG2, Miapaca-2, HCC827, Hela, A549, AGS, and HT-29 cell lines in vitro. An oxidized derivative, 10, was found to possess strong inhibition and anti-migration properties in the HCC827 cell line and serves as a potential lead compound for the development of new anticancer drugs. In addition, structure-activity relationships (SAR) were also evaluated to provide key information for future anticancer drug development.

Keywords: Cytotoxicity; Derivatives; HCC827 cell line; Modification; Oblongifolin C; Structure–activity relationships; c-Met kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemical synthesis
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Benzophenones / chemical synthesis
  • Benzophenones / chemistry
  • Benzophenones / pharmacology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Garcinia / chemistry
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Neoplasms / drug therapy
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / metabolism
  • Structure-Activity Relationship
  • Terpenes / chemical synthesis
  • Terpenes / chemistry*
  • Terpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Benzophenones
  • Protein Kinase Inhibitors
  • Terpenes
  • oblongifolin C
  • benzophenone
  • MET protein, human
  • Proto-Oncogene Proteins c-met