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Please use this identifier to cite or link to this item: http://dspace.utalca.cl/handle/1950/8904

Title: Gastroprotective Effect and Cytotoxicity of Labdeneamides with Amino Acids
Authors: Schmeda-Hirschmann, G.
Rodriguez, J.A.
Theoduloz, C.
Valderrama, J.A.
Keywords: amino acid amides
Araucaria araucana
gastroprotective effect
labdane diterpenes
Issue Date: Mar-2011
Citation: PLANTA MEDICA Volume: 77 Issue: 4 Pages: 340-345 DOI: 10.1055/s-0030-1250323
Abstract: Semisynthetic aromatic amides from Araucaria araucana diterpene acids have been shown to display a relevant gastroprotective effect with low cytotoxicity. The aim of this work was to assess the gastroprotective effect of amino acid amides from imbricatolic acid and its 8(9)-en isomer in the ethanol/HCl-induced gastric lesions model in mice as well as to determine the cytotoxicity of the obtained compounds on the following human cell lines: normal lung fibroblasts (MRC-5), gastric adenocarcinoma (AGS), and liver hepatocellular carcinoma (Hep G2). The diterpenes 15-acetoxyimbricatolic acid, its 8(9)-en isomer, 15-hydroxyimbricatolic acid, and the 8(9)-en derivative, bearing a COOH function at C-19, were used as starting compounds. New amides with C-protected amino acids were prepared. The study reports the effect of a single oral administration of either compound 50 min before the induction of gastric lesions by ethanol/HCl. Some 20 amino acid monoamides were obtained. Dose-response experiments on the glycyl derivatives showed that at a single oral dose of 100 mg/kg, the compounds presented an effect comparable to the reference drug lansoprazole at 20 mg/kg and at 50 mg/kg reduced gastric lesions by about 50%. All derivatives obtained in amounts >30 mg were compared at a single oral dose of 50 mg/kg. The best gastroprotective effect was observed for the exomethylene derivatives bearing a valine residue at C-19 either with an acetoxy or free hydroxy group at C-15. The tryptophanyl derivative from the acetate belonging to the 8,9-en series presented selective cytotoxicity against hepatocytes. The glycyl amide of 15-acetoxyimbricatolic acid was the most cytotoxic and less selective compound with IC50 values between 47 and 103 mu M for the studied cell lines. This is the first report on the obtention of semisynthetic amino acid amides from labdane diterpenes.
Description: Schmeda-Hirschmann, G (Schmeda-Hirschmann, Guillermo)1; Rodriguez, JA (Rodriguez, Jaime A.)2; Theoduloz, C (Theoduloz, Cristina)2; ..............1. Univ Talca, Lab Quim Prod Nat, Inst Quim Recursos Nat, Talca, Chile 2. Univ Talca, Depto Bioquim Clin, Fac Ciencias Salud, Talca, Chile
URI: http://dspace.utalca.cl/handle/1950/8904
ISSN: 0032-0943
Appears in Collections:Artículos en publicaciones ISI - Universidad de Talca

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