Synthesis and antitumor activity evaluation of maleopimaric acid N-aryl imide atropisomers

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6755-8. doi: 10.1016/j.bmcl.2013.10.028. Epub 2013 Oct 25.

Abstract

Maleopimaric acid N-aryl imides (2) and methyl maleopimaric acid N-aryl imides (3) were designed and synthesized. Their atropisomers (A and B) were separated into their enantiomeric pure forms and the anti-proliferative activity was tested against NCI, A549, Hep G-2, MGC-803 and Hct-116 cell lines, respectively. A significant difference in the level of cytotoxicity was observed between R and S conformers. Atropisomers A with an R configuration exhibited significant toxicity (the IC50 values ranging from 7.51 to 32.1 μM). Further experiments proved that antitumor activity of 2A was achieved through the induction of cell apoptosis by G1 cell-cycle arrest.

Keywords: Apoptosis; Atropisomers; Cytotoxicity; Diimides; Maleopimaric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • HCT116 Cells
  • Hep G2 Cells
  • Humans
  • Imides / chemical synthesis
  • Imides / chemistry*
  • Imides / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Stereoisomerism
  • Triterpenes / chemistry*

Substances

  • Antineoplastic Agents
  • Imides
  • Triterpenes
  • maleopimaric acid