Gastroprotective activity and cytotoxic effect of cyperenoic acid derivatives.
The gastroprotective effect of the sesquiterpene cyperenoic acid and seven semi-synthetic derivatives was assessed in the HCl/ethanol-induced gastric ulcer model in mice. At doses of 25, 50 and 100 mg kg(-1), cyperenoic acid showed a dose-dependent gastroprotective effect reducing the lesions by 45 and 75% at 50 and 100 mg kg(-1), respectively. Seven derivatives of the sesquiterpene were prepared and their gastroprotective activity compared at 50 mg kg(-1). The cytotoxicity of the compounds was evaluated in fibroblasts and AGS cells. At 50 mg kg(-1), patchoulan-15-oic acid (compound 8) presented the best gastroprotective effect, reducing the gastric lesions by 86%, with a similar effect to lansoprazole at 20 mg kg(-1). The gastroprotective effect of cyperenol, cyperenoic acid methyl ester and the ethylamide and butylamide from cyperenoic acid were in the same range, reducing the gastric lesions by 72-77%. Cyperenol and cyperenoic acid methyl ester, however, were more cytotoxic with IC50 (concentration that produces a 50% inhibitory effect) values of 44 and 75, 48 and 75 microM against AGS cells and fibroblasts, respectively. The best gastroprotective effect with lower cytotoxicity was found for the compound 8, cyperenoic acid and the p-anisidyl derivative 7.
Pertino
Mariano
M
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile.
Rodríguez
Jaime A
JA
Theoduloz
Cristina
C
Razmilic
Iván
I
Schmeda-Hirschmann
Guillermo
G
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006801:Humans; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000633:toxicity; D020128:Inhibitory Concentration 50; D031286:Jatropha / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D018675:Toxicity Tests / Q000379:methods
D000897:Anti-Ulcer Agents; D010936:Plant Extracts; D012717:Sesquiterpenes; C519558:cyperenoic acid; D000431:Ethanol; D006851:Hydrochloric Acid