Metabolism and biological production of resolvins derived from docosapentaenoic acid (DPAn-6)
| 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 |
| ResultId |
1 |
|---|---|
| Header |
edsair OpenAIRE edsair.doi.dedup.....6e239afe0ae82b7772a4f4c0faea7926 793 3 unknown 793.324279785156 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsair&AN=edsair.doi.dedup.....6e239afe0ae82b7772a4f4c0faea7926&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e239afe0ae82b7772a4f4c0faea7926# [Name] => EDS - OpenAIRE [Category] => fullText [Text] => View record in OpenAIRE [MouseOverText] => View record in OpenAIRE ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Metabolism and biological production of resolvins derived from docosapentaenoic acid (DPAn-6)
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Marcus+Obeng%22">Marcus Obeng</searchLink><br /><searchLink fieldCode="AR" term="%22Gloria+Chung%22">Gloria Chung</searchLink><br /><searchLink fieldCode="AR" term="%22Eileen+Bailey-Hall%22">Eileen Bailey-Hall</searchLink><br /><searchLink fieldCode="AR" term="%22Linda+M%2E+Arterburn%22">Linda M. Arterburn</searchLink><br /><searchLink fieldCode="AR" term="%22Todd+Hallenbeck%22">Todd Hallenbeck</searchLink><br /><searchLink fieldCode="AR" term="%22Julie+M%2E+Nauroth%22">Julie M. Nauroth</searchLink><br /><searchLink fieldCode="AR" term="%22Bindi+Dangi%22">Bindi Dangi</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => <i>Biochemical Pharmacology</i>. 79:251-260 ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Elsevier BV, 2010. ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2010 ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22Male%22">Male</searchLink><br /><searchLink fieldCode="DE" term="%22Drug%22">Drug</searchLink><br /><searchLink fieldCode="DE" term="%22Docosahexaenoic+Acids%22">Docosahexaenoic Acids</searchLink><br /><searchLink fieldCode="DE" term="%22Stereochemistry%22">Stereochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolite%22">Metabolite</searchLink><br /><searchLink fieldCode="DE" term="%22media%5Fcommon%2Equotation%5Fsubject%22">media_common.quotation_subject</searchLink><br /><searchLink fieldCode="DE" term="%22Anti-Inflammatory+Agents%22">Anti-Inflammatory Agents</searchLink><br /><searchLink fieldCode="DE" term="%22Biology%22">Biology</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemistry%22">Biochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Rats%2C+Sprague-Dawley%22">Rats, Sprague-Dawley</searchLink><br /><searchLink fieldCode="DE" term="%22chemistry%2Echemical%5Fcompound%22">chemistry.chemical_compound</searchLink><br /><searchLink fieldCode="DE" term="%22Tandem+Mass+Spectrometry%22">Tandem Mass Spectrometry</searchLink><br /><searchLink fieldCode="DE" term="%22Animals%22">Animals</searchLink><br /><searchLink fieldCode="DE" term="%22Humans%22">Humans</searchLink><br /><searchLink fieldCode="DE" term="%22Cells%2C+Cultured%22">Cells, Cultured</searchLink><br /><searchLink fieldCode="DE" term="%22Chromatography%2C+High+Pressure+Liquid%22">Chromatography, High Pressure Liquid</searchLink><br /><searchLink fieldCode="DE" term="%22media%5Fcommon%22">media_common</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacology%22">Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22chemistry%2Echemical%5Fclassification%22">chemistry.chemical_classification</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolism%22">Metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Oxylipin%22">Oxylipin</searchLink><br /><searchLink fieldCode="DE" term="%22Rats%22">Rats</searchLink><br /><searchLink fieldCode="DE" term="%22Enzyme%22">Enzyme</searchLink><br /><searchLink fieldCode="DE" term="%22chemistry%22">chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Docosahexaenoic+acid%22">Docosahexaenoic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Fatty+Acids%2C+Unsaturated%22">Fatty Acids, Unsaturated</searchLink><br /><searchLink fieldCode="DE" term="%22Microsomes%2C+Liver%22">Microsomes, Liver</searchLink><br /><searchLink fieldCode="DE" term="%22Docosapentaenoic+acid%22">Docosapentaenoic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Resolvin%22">Resolvin</searchLink><br /><searchLink fieldCode="DE" term="%22Chromatography%2C+Liquid%22">Chromatography, Liquid</searchLink><br /><searchLink fieldCode="DE" term="%22Half-Life%22">Half-Life</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => 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. ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 0006-2952 ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.1016/j.bcp.2009.08.001 ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e239afe0ae82b7772a4f4c0faea7926" linkWindow="_blank">https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e239afe0ae82b7772a4f4c0faea7926</link><br /><link linkTarget="URL" linkTerm="https://doi.org/10.1016/j.bcp.2009.08.001" linkWindow="_blank">https://doi.org/10.1016/j.bcp.2009.08.001</link> ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => CLOSED ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsair.doi.dedup.....6e239afe0ae82b7772a4f4c0faea7926 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1016/j.bcp.2009.08.001
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => Undetermined
)
)
[PhysicalDescription] => Array
(
[Pagination] => Array
(
[PageCount] => 10
[StartPage] => 251
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => Male
[Type] => general
)
[1] => Array
(
[SubjectFull] => Drug
[Type] => general
)
[2] => Array
(
[SubjectFull] => Docosahexaenoic Acids
[Type] => general
)
[3] => Array
(
[SubjectFull] => Stereochemistry
[Type] => general
)
[4] => Array
(
[SubjectFull] => Metabolite
[Type] => general
)
[5] => Array
(
[SubjectFull] => media_common.quotation_subject
[Type] => general
)
[6] => Array
(
[SubjectFull] => Anti-Inflammatory Agents
[Type] => general
)
[7] => Array
(
[SubjectFull] => Biology
[Type] => general
)
[8] => Array
(
[SubjectFull] => Biochemistry
[Type] => general
)
[9] => Array
(
[SubjectFull] => Rats, Sprague-Dawley
[Type] => general
)
[10] => Array
(
[SubjectFull] => chemistry.chemical_compound
[Type] => general
)
[11] => Array
(
[SubjectFull] => Tandem Mass Spectrometry
[Type] => general
)
[12] => Array
(
[SubjectFull] => Animals
[Type] => general
)
[13] => Array
(
[SubjectFull] => Humans
[Type] => general
)
[14] => Array
(
[SubjectFull] => Cells, Cultured
[Type] => general
)
[15] => Array
(
[SubjectFull] => Chromatography, High Pressure Liquid
[Type] => general
)
[16] => Array
(
[SubjectFull] => media_common
[Type] => general
)
[17] => Array
(
[SubjectFull] => Pharmacology
[Type] => general
)
[18] => Array
(
[SubjectFull] => chemistry.chemical_classification
[Type] => general
)
[19] => Array
(
[SubjectFull] => Metabolism
[Type] => general
)
[20] => Array
(
[SubjectFull] => Oxylipin
[Type] => general
)
[21] => Array
(
[SubjectFull] => Rats
[Type] => general
)
[22] => Array
(
[SubjectFull] => Enzyme
[Type] => general
)
[23] => Array
(
[SubjectFull] => chemistry
[Type] => general
)
[24] => Array
(
[SubjectFull] => Docosahexaenoic acid
[Type] => general
)
[25] => Array
(
[SubjectFull] => Fatty Acids, Unsaturated
[Type] => general
)
[26] => Array
(
[SubjectFull] => Microsomes, Liver
[Type] => general
)
[27] => Array
(
[SubjectFull] => Docosapentaenoic acid
[Type] => general
)
[28] => Array
(
[SubjectFull] => Resolvin
[Type] => general
)
[29] => Array
(
[SubjectFull] => Chromatography, Liquid
[Type] => general
)
[30] => Array
(
[SubjectFull] => Half-Life
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Metabolism and biological production of resolvins derived from docosapentaenoic acid (DPAn-6)
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Marcus Obeng
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Gloria Chung
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Eileen Bailey-Hall
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Linda M. Arterburn
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Todd Hallenbeck
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Julie M. Nauroth
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Bindi Dangi
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2010
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 00062952
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsair
)
)
[Numbering] => Array
(
[0] => Array
(
[Type] => volume
[Value] => 79
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Biochemical Pharmacology
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |