Document Detail

Gastroprotective and cytotoxic effect of dehydroabietic acid derivatives.
MedLine Citation:
PMID:  16125407     Owner:  NLM     Status:  MEDLINE    
Dehydroabietic acid derivatives have been reported to display antisecretory and antipepsin effect in animal models. Some 19 dehydroabietic acid diterpenes were prepared and assessed for gastroprotective activity in the HCl/EtOH-induced gastric lesions in mice as well as for cytotoxicity in human lung fibroblasts (MRC-5) and human epithelial gastric (AGS) cells. At a single oral dose of 100 mg kg(-1), highest gastroprotective effect was provided by dehydroabietanol, its corresponding aldehyde, dehydroabietic acid (DHA) and its methyl ester, N-(m-nitrophenyl)-, N-(o-chlorophenyl)- and N-(p-iodophenyl)abieta-8,11,13-trien-18-amide (compounds 12-14), N-2-aminothiazolyl- and N-benzylabieta-8,11,13-trien-18-amide (compounds 18-19) being as active as lansoprazole at 20 mg kg(-1) and reducing the lesion index by at least 75%. In the compound series including the alcohol, ester, aldehyde, acid and methyl ester at C-18 (compounds 1-9), highest activity was related with the presence of an alcohol, aldehyde, acid or methyl ester at C-18, the activity being strongly reduced after esterification. The cytotoxicity of the compounds 1-9 towards AGS cells and fibroblasts was higher than the values for the amides 10-19. In the compounds 10-19, the best gastroprotective effect was observed for the aromatic amides 12-14 (75-85% inhibition of gastric lesions) bearing a nitro or halogen function in the N-benzoyl moiety. Lowest cytotoxicity was found for the amides, with IC(50) values >1000 microM for fibroblasts and from 200 up to >1000 microM for AGS cells, respectively. The N-2-aminothiazolyl- and N-benzylamide derivatives were also very active as gastroprotectors with higher cytotoxicity against AGS cells.
Beatriz Sepúlveda; Luis Astudillo; Jaime A Rodríguez; Tania Yáñez; Cristina Theoduloz; Guillermo Schmeda-Hirschmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-24
Journal Detail:
Title:  Pharmacological research : the official journal of the Italian Pharmacological Society     Volume:  52     ISSN:  1043-6618     ISO Abbreviation:  Pharmacol. Res.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-31     Completed Date:  2006-02-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8907422     Medline TA:  Pharmacol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  429-37     Citation Subset:  IM    
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Talca, Chile.
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MeSH Terms
Cell Line
Cell Survival / drug effects*
Diterpenes / pharmacology*
Diterpenes, Abietane / pharmacology*
Dose-Response Relationship, Drug
Fibroblasts / drug effects
Gastric Mucosa / drug effects*
Structure-Activity Relationship
Reg. No./Substance:
0/Diterpenes; 0/Diterpenes, Abietane; 1740-19-8/dehydroabietic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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