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Please use this identifier to cite or link to this item: http://dspace.utalca.cl/handle/1950/4587

Title: Gastroprotective and cytotoxic effect of semisynthetic ferruginol derivatives
Authors: Areche, C.
Rodriguez, J.
Razmilic, I.
Yanez, T.
Theoduloz, C.
Schmeda-Hirschmann, G.
Issue Date: 2007
Publisher: Pharmaceutical Press
Citation: Journal of Pharmacy and Pharmacology 59 (2): 289-300
Abstract: The gastroprotective abietane diterpene ferruginol has been shown to present high cytotoxicity. In order to obtain active compounds with less cytotoxicity, 18 semisynthetic ferruginol derivatives and totarol were assessed for their gastroprotective effects in the HCl/ethanol-induced gastric lesion model in mice, as well as for cytotoxicity in human gastric epithelial cells (AGS) and human lung fibroblasts (MRC-5). At 20 mg kg−1, the greatest gastroprotective effects were provided by abieta-8,11,13-triene (1), abieta-8,11,13-trien-12-yl-2-chloropropanoate (8), abieta-8,11,13-trien-12-yl propenoate (9), 12-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-abieta-8,11,13-triene (17) and 12-(β-D-galactopyranosyloxy)-abieta-8,11,13-triene (18), all of which were as active as the reference drug lansoprazole at 20 mg kg−1, reducing gastric lesions by 69, 76, 67, 72 and 61%, respectively. No relation was observed between lipophilicity and the gastroprotective effect. Compounds that showed the greatest cytotoxicity towards AGS cells were ferruginol (2), the corresponding formate (5), acetate (6), propionate (7), 8, 9, 12-(β-D-glucopyranosyloxy)-abieta-8,11,13-triene (16), 18 and totarol (20) (IC50 18-44 μM). Ferruginol and compounds 5-9, 16, 18 and 20 were the most toxic compounds against fibroblasts (IC50 19-56 μM), with a correlation to AGS cells. The derivative 19 was much more active against AGS cells than towards fibroblasts. The best activity/cytotoxicity ratio was found for compound 17, with a lesion index comparable with lansoprazole at 20 mg kg−1 and cytotoxicity >1000 μM towards MRC-5 and AGS cells, respectively. In conclusion, some derivatives showed a better gastroprotective effect/cytotoxicity ratio than the parent compound ferruginol. A total of 13 new compounds are reported here for the first time
Description: Areche, Carlos; Razmilic, Iván; Schmeda-Hirschmann, Guillermo. Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile. Rodríguez, Jaime A.; Yáñez, Tania; Theoduloz, Cristina. Departamento de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad de Talca, Casilla 747, Talca, Chile.
URI: http://dspace.utalca.cl/handle/1950/4587
ISSN: 0022-3573
Appears in Collections:Artículos en publicaciones ISI - Universidad de Talca

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