Document Detail


Metabolism and biological production of resolvins derived from docosapentaenoic acid (DPAn-6).
MedLine Citation:
PMID:  19679107     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
17S-HDPAn-6 (17S-hydroxydocosa-4Z,7Z,10Z,13Z,15E-pentaenoic acid) and 10S,17S-HDPAn-6 (10S,17S-dihydroxydocosa-4Z,7Z,11E,13Z,15E-pentaenoic acid) are potent anti-inflammatory resolvins derived from DPAn-6 (docosapentaenoic acid n-6) and are analogous in structure and action to DHA (docosahexaenoic acid)-derived resolvins. These resolvins have proven to be potential drug candidates, albeit with therapeutic profiles that need optimization. The main objectives of this study were to evaluate key features of DPAn-6 derived resolvins that are important for therapeutic efficacy, demonstrate that these DPAn-6 resolvins could be produced naturally, and could therefore have physiological significance. Here we demonstrate biological production, examine pharmacokinetic profiles and identify key routes of metabolic inactivation of DPAn-6 derived resolvins. We compare their metabolic stability to a known resolvin, 17S-HDHA (17S-hydroxydocosa-4Z,7Z,10Z,13Z,15E,19Z-hexaenoic acid) and show that order of their stabilities is 10S,17S-HDPAn-6>17S-HDPAn-6>17S-HDHA. We show that both these compounds are not strong inhibitors of cytochrome-P450 enzymes. We evaluate activity of compounds in the delayed-type hypersensitivity model, results of which show that compounds need optimization for enhanced duration and magnitude of action. Analysis of the metabolic stability and identification of metabolites of these compounds could play an important role in the design of better analogs with longer durations of action and hence better efficacy.
Authors:
Bindi Dangi; Marcus Obeng; Julie M Nauroth; Gloria Chung; Eileen Bailey-Hall; Todd Hallenbeck; Linda M Arterburn
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Publication Detail:
Type:  Journal Article     Date:  2009-08-11
Journal Detail:
Title:  Biochemical pharmacology     Volume:  79     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2009-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  251-60     Citation Subset:  IM    
Affiliation:
Martek Biosciences Corp., 6480 Dobbin Road, Columbia, MD 21045, USA. bdangi@martek.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / metabolism*,  pharmacokinetics
Cells, Cultured
Chromatography, High Pressure Liquid
Chromatography, Liquid
Docosahexaenoic Acids / metabolism*,  pharmacokinetics
Fatty Acids, Unsaturated / chemistry,  metabolism*
Half-Life
Humans
Male
Microsomes, Liver / metabolism
Rats
Rats, Sprague-Dawley
Tandem Mass Spectrometry
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Fatty Acids, Unsaturated; 25167-62-8/Docosahexaenoic Acids; 25448-00-4/docosapentaenoic acid

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


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