Document Detail


Synthesis of isoornithines and methylputrescines. An evaluation of their inhibitory effects on ornithine decarboxylase.
MedLine Citation:
PMID:  7473562     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
2-(Aminomethyl)-4-aminobutyric acid (isoornithine), 3-methylisoornithine, and 2,3-dimethylisoornithine were not decarboxylated by liver ornithine decarboxylase (ODC, EC 4.1.1.17) of thioacetamide-treated rats but were good competitive inhibitors of the enzyme (Ki ranged from 0.72 to 1.79 mM). When assayed in vivo in the treated rats, the above mentioned isoornithines were also found to inhibit liver ODC when administered 1 h before sacrifice. When the methylputrescines formally derived from the decarboxylation of several isoornithines were assayed on rat liver ODC, it was found that only 2,3-dimethylputrescine decreased the enzymatic activity. When assayed in vivo, it was found to decrease ODC activity by 60%, when the latter was measured 1 h after administration. The effect was reverted 4 h after administration of the drug. Isoornithines were not taken up by H-35 hepatoma cells; hence they did not affect their ODC activity. 2,3-Dimethylputrescine however, was transported into the cells and significantly decreased its ODC activity.
Authors:
G Aizencang; R B Frydman; S Giorgieri; L Sambrotta; L Guerra; B Frydman
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  38     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1995 Oct 
Date Detail:
Created Date:  1995-11-28     Completed Date:  1995-11-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4337-41     Citation Subset:  IM    
Affiliation:
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Binding, Competitive
Carcinoma, Hepatocellular
Enzyme Inhibitors / pharmacology*
Liver / drug effects,  enzymology
Liver Neoplasms
Ornithine / analogs & derivatives*,  chemistry*,  metabolism
Ornithine Decarboxylase / antagonists & inhibitors*
Putrescine / analogs & derivatives*,  chemistry*,  metabolism
Rats
Structure-Activity Relationship
Thioacetamide / pharmacology
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 110-60-1/Putrescine; 62-55-5/Thioacetamide; 7006-33-9/Ornithine; EC 4.1.1.17/Ornithine Decarboxylase

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


Previous Document:  Mechanism of inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)p...
Next Document:  Synthesis and structure-activity relationships of substituted 1,4-dihydroquinoxaline-2,3-diones: ant...