Synthesis and evaluation of a novel series of heterocyclic oleanolic acid derivatives with anti-osteoclast formation activity

Eur J Med Chem. 2009 Jul;44(7):2796-806. doi: 10.1016/j.ejmech.2008.12.024. Epub 2008 Dec 31.

Abstract

Oleanolic acid with anti-bone resorption effect was an active component discovered in a medicinal plant of Achyranthes bidentata. A series of heterocyclic derivatives of oleanolic acid including indole, pyrazine, quinoxaline, quinoline moieties and their natural amino acid amides were synthesized. Their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) and cytotoxicity of the selected derivatives were evaluated. Among the derivatives, compounds 2a and 8a displayed quite a potent activity even at 200 nM. The structure-activity relationships of the derivatives were also discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Animals
  • Cell Survival / drug effects
  • Drug Design*
  • Heterocyclic Compounds / chemistry*
  • Male
  • Mice
  • Oleanolic Acid / analogs & derivatives
  • Oleanolic Acid / chemical synthesis*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology*
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Heterocyclic Compounds
  • Oleanolic Acid