Gastroprotective effect of carnosic acid gamma-lactone derivatives.
Carnosic acid (1) has been shown to possess gastroprotective activity in vitro and in vivo. However, little is known of the gastroprotective effect or cytotoxicity of carnosic acid gamma-lactone (3). To determine structure-activity relationships, a series of 17 esters of 3 were prepared including aliphatic, aromatic, and heterocyclic derivatives. Also, two units of 3 were coupled with succinic and phthalic acid as linkers. The compounds were assessed for their gastroprotective effect in the HCl/EtOH-induced gastric lesions model in mice and for cytotoxicity in human lung fibroblasts, human adenocarcinoma AGS cells, and Hep G2 hepatocellular carcinoma cells. At a single oral dose of 40 mg/kg, the gastroprotective effect increased moderately with the length of the alkyl chain. The best effects were observed for the butyrate (9) and chloroacetate (6) derivatives. Activity of fatty acid esters increased with chain length but decreased with unsaturation. The best gastroprotective effect, with lowest cytotoxicity, was found for the palmitate (11) and oleate (12) derivatives.
Pertino
Mariano Walter
MW
Laboratorio de Quimica de Productos Naturales, Instituto de Quimica de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile.
Theoduloz
Cristina
C
Rodríguez
Jaime A
JA
Yáñez
Tania
T
Lazo
Viviana
V
Schmeda-Hirschmann
Guillermo
G
D045784:Abietanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D019301:Oleic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010168:Palmitates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D045784:Abietanes; D000897:Anti-Ulcer Agents; D007783:Lactones; D010168:Palmitates; D010936:Plant Extracts; D019301:Oleic Acid; C018381:salvin