Document Detail


Gastroprotective and cytotoxic effect of dehydroabietic acid derivatives.
MedLine Citation:
PMID:  16125407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Beatriz Sepúlveda; Luis Astudillo; Jaime A Rodríguez; Tania Yáñez; Cristina Theoduloz; Guillermo Schmeda-Hirschmann
Related Documents :
3209657 - Gas chromatographic analysis of histidine: effect on other amino acids present.
10867247 - Stability of some novel thymidine, 5-bromo-2'-deoxyuridine and 3'-azido-2'-3'-dideoxyth...
10218837 - Synthesis and evaluation of amino acid esters of 6-deoxypenciclovir as potential prodru...
17540117 - Synthesis and characterization of functional elastomeric poly(ester amide) co-polymers.
12706457 - Relative potencies of statins in reducing cholesterol synthesis and enhancing linoleic ...
6326727 - Adrenomyeloneuropathy--clinical and biochemical diagnosis.
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    
Affiliation:
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Talca, Chile.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Survival / drug effects*
Diterpenes / pharmacology*
Diterpenes, Abietane / pharmacology*
Dose-Response Relationship, Drug
Fibroblasts / drug effects
Gastric Mucosa / drug effects*
Humans
Male
Mice
Structure-Activity Relationship
Chemical
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


Previous Document:  Low atmospheric temperature dependence on photodegradation of wood.
Next Document:  Rapid and easy thermodynamic optimization of the 5'-end of mRNA dramatically increases the level of ...