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

Gayathri Chadalapaka, Indira Jutooru, Alan McAlees, Tom Stefanac, Stephen Safe

Research output: Contribution to journalArticle

90 Scopus citations

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 IC50 values were highly variable and dependent on the 2-substituent (CN vs CF3) and cancer cell context.

Original languageEnglish (US)
Pages (from-to)2633-2639
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number8
DOIs
StatePublished - Apr 15 2008

Keywords

  • Bladder cancer
  • Glycyrrhetinate analogs
  • Growth inhibition
  • Pancreatic cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives'. Together they form a unique fingerprint.

Cite this