Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2633-9. doi: 10.1016/j.bmcl.2008.03.031. Epub 2008 Mar 14.

Abstract

Derivatives of oleanolic acid, ursolic acid and glycyrrhetinic acid substituted with electron-withdrawing groups at the 2-position in the A-ring which also contains a 1-en-3-one structure are potent inhibitors of cancer cell growth. In this study, we have compared the effects of several 2-substituted analogs of triterpenoid acid methyl esters derived from ursolic and glycyrrhetinic acid on proliferation of KU7 and 253JB-V bladder and Panc-1 and Panc-28 pancreatic cancer cells. The results show that the 2-cyano and 2-trifluoromethyl derivatives were the most active compounds. The glycyrrhetinic acid derivatives with the rearranged C-ring containing the 9(11)-en-12-one structure were generally more active than the corresponding 12-en-11-one isomers. However, differences in growth inhibitory IC(50) values were highly variable and dependent on the 2-substituent (CN vs CF(3)) and cancer cell context.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Glycyrrhetinic Acid / chemical synthesis*
  • Glycyrrhetinic Acid / chemistry
  • Glycyrrhetinic Acid / pharmacology*
  • Humans
  • Methylation
  • Molecular Structure
  • Pancreatic Neoplasms / pathology*
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Triterpenes
  • ursolic acid
  • Glycyrrhetinic Acid