Metabolism and biological production of resolvins derived from docosapentaenoic acid (DPAn-6)

التفاصيل البيبلوغرافية
العنوان: Metabolism and biological production of resolvins derived from docosapentaenoic acid (DPAn-6)
المؤلفون: Marcus Obeng, Gloria Chung, Eileen Bailey-Hall, Linda M. Arterburn, Todd Hallenbeck, Julie M. Nauroth, Bindi Dangi
المصدر: Biochemical Pharmacology. 79:251-260
بيانات النشر: Elsevier BV, 2010.
سنة النشر: 2010
مصطلحات موضوعية: Male, Drug, Docosahexaenoic Acids, Stereochemistry, Metabolite, media_common.quotation_subject, Anti-Inflammatory Agents, Biology, Biochemistry, Rats, Sprague-Dawley, chemistry.chemical_compound, Tandem Mass Spectrometry, Animals, Humans, Cells, Cultured, Chromatography, High Pressure Liquid, media_common, Pharmacology, chemistry.chemical_classification, Metabolism, Oxylipin, Rats, Enzyme, chemistry, Docosahexaenoic acid, Fatty Acids, Unsaturated, Microsomes, Liver, Docosapentaenoic acid, Resolvin, Chromatography, Liquid, Half-Life
الوصف: 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.
تدمد: 0006-2952
DOI: 10.1016/j.bcp.2009.08.001
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e239afe0ae82b7772a4f4c0faea7926
https://doi.org/10.1016/j.bcp.2009.08.001
Rights: CLOSED
رقم الانضمام: edsair.doi.dedup.....6e239afe0ae82b7772a4f4c0faea7926
قاعدة البيانات: OpenAIRE
الوصف
تدمد:00062952
DOI:10.1016/j.bcp.2009.08.001