Rapid evaluation of Antrodia camphorata natural products and derivatives in tumourigenic liver progenitor cells with a novel cell proliferation assay

ChemMedChem. 2009 Oct;4(10):1657-67. doi: 10.1002/cmdc.200900238.

Abstract

We report the syntheses of five natural product maleimide and maleic anhydrides from the mushroom Antrodia camphorata. The ability of these compounds to affect proliferation in non-tumourigenic and tumourigenic liver progenitor cell lines was monitored by the Cellscreen system, a novel and nondestructive rapid-screening instrument. Additionally, a range of new aryl-functionalised differentiated derivatives were prepared through a Suzuki cross-coupling reaction to influence cell-growth effects. Several derivatives radically slowed the proliferation of liver progenitor cells; however, of particular interest were two maleic anhydride derivatives containing aryl tethers. These analogues demonstrated selectivity for limiting the proliferation of tumourigenic progenitor cells in comparison with their non-tumourigenic counterparts. Also highlighted is the application of the Cellscreen system in medicinal chemistry to rapidly measure the effect of compound libraries on cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antrodia / chemistry*
  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Cell Proliferation / drug effects
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Maleic Anhydrides / chemical synthesis
  • Maleic Anhydrides / chemistry
  • Maleic Anhydrides / pharmacology*
  • Maleimides / chemical synthesis
  • Maleimides / chemistry
  • Maleimides / pharmacology*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology
  • Tumor Stem Cell Assay*

Substances

  • Antineoplastic Agents
  • Biological Products
  • Maleic Anhydrides
  • Maleimides