Gastroprotective Effect and Cytotoxicity of Labdeneamides with Amino Acids

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dc.contributor.authorSchmeda Hirschmann, Guillermo
dc.contributor.authorRodriguez, Jaime A.
dc.contributor.authorTheoduloz, Cristina
dc.contributor.authorValderrama, Jaime A.
dc.date.accessioned2024-01-10T12:05:40Z
dc.date.available2024-01-10T12:05:40Z
dc.date.issued2011
dc.description.abstractSemisynthetic 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.
dc.description.funderFONDECYT
dc.description.funderUniversidad de Talca
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent6 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1055/s-0030-1250323
dc.identifier.issn0032-0943
dc.identifier.pubmedidMEDLINE:20862639
dc.identifier.urihttps://doi.org/10.1055/s-0030-1250323
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76049
dc.identifier.wosidWOS:000288116200005
dc.information.autorucQuímica;Valderrama J;S/I;98772
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final345
dc.pagina.inicio340
dc.publisherGEORG THIEME VERLAG KG
dc.revistaPLANTA MEDICA
dc.rightsacceso restringido
dc.subjectamino acid amides
dc.subjectAraucaria araucana
dc.subjectAraucariaceae
dc.subjectcytotoxicity
dc.subjectgastroprotective effect
dc.subjectlabdane diterpenes
dc.subjectARAUCARIA-ARAUCANA RESIN
dc.subjectINDUCED GASTRIC-LESIONS
dc.subjectSALVINORIN-A ANALOGS
dc.subjectANTIULCER ACTIVITY
dc.subjectCROTON-CAJUCARA
dc.subjectMONOSODIUM SALT
dc.subjectDERIVATIVES
dc.subjectSOLIDAGENONE
dc.subjectRATS
dc.subjectULCER
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGastroprotective Effect and Cytotoxicity of Labdeneamides with Amino Acids
dc.typeartículo
dc.volumen77
sipa.codpersvinculados98772
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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