Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives.
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.
Chadalapaka
Gayathri
G
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
Jutooru
Indira
I
McAlees
Alan
A
Stefanac
Tom
T
Safe
Stephen
S
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000473:pathology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D000097245:Ursolic Acid
D006034:Glycyrrhetinic Acid; D014315:Triterpenes; D000097245:Ursolic Acid