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Identification of a Tryptanthrin Metabolite in Rat Liver Microsomes by Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry
Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses. To characterize phase I metabolite(s), tryptanthrin was incubated...
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| Published in: | Biological & Pharmaceutical Bulletin 2007/10/01, Vol.30(10), pp.1991-1995 |
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| Main Authors: | , , , , , |
| Format: | Article |
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| cited_by | cdi_FETCH-LOGICAL-c690t-28aebb99c2def898b379aab8b6bd530e091063dc00d8304ad9048acd98140c0d3 |
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| cites | cdi_FETCH-LOGICAL-c690t-28aebb99c2def898b379aab8b6bd530e091063dc00d8304ad9048acd98140c0d3 |
| container_end_page | 1995 |
| container_issue | 10 |
| container_start_page | 1991 |
| container_title | Biological & Pharmaceutical Bulletin |
| container_volume | 30 |
| creator | Lee, Sang Kyu Kim, Ghee Hwan Kim, Dong Hyeon Kim, Dong Hyun Jahng, Yurngdong Jeong, Tae Cheon |
| description | Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses. To characterize phase I metabolite(s), tryptanthrin was incubated with rat liver microsomes in the presence of NADPH-generating system. One metabolite was identified by liquid chromatography/electrospray ionization-tandem mass spectrometry. M1 could be identified as a metabolite mono-hydroxylated on the aromatic ring of indole moiety from the MS2 spectra of protonated tryptanthrin and M1. The structure of metabolite was confirmed as 8-hydroxytryptanthrin with a chemically synthesized authentic standard. The formation of M1 was NADPH-dependent and was inhibited by SKF-525A, a general CYP-inhibitor, indicating the cytochrome P450 (CYP)-mediated reaction. In addition, it was proposed that M1 might be formed by CYP 1A in rat liver microsomes from the experiments with enriched rat liver microsomes. |
| doi_str_mv | 10.1248/bpb.30.1991 |
| format | article |
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To characterize phase I metabolite(s), tryptanthrin was incubated with rat liver microsomes in the presence of NADPH-generating system. One metabolite was identified by liquid chromatography/electrospray ionization-tandem mass spectrometry. M1 could be identified as a metabolite mono-hydroxylated on the aromatic ring of indole moiety from the MS2 spectra of protonated tryptanthrin and M1. The structure of metabolite was confirmed as 8-hydroxytryptanthrin with a chemically synthesized authentic standard. The formation of M1 was NADPH-dependent and was inhibited by SKF-525A, a general CYP-inhibitor, indicating the cytochrome P450 (CYP)-mediated reaction. In addition, it was proposed that M1 might be formed by CYP 1A in rat liver microsomes from the experiments with enriched rat liver microsomes.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.30.1991</identifier><identifier>PMID: 17917280</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - analysis ; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics ; Biotransformation ; Chromatography, High Pressure Liquid ; Cytochrome P-450 Enzyme Inhibitors ; cytochrome P450 (CYP) ; Enzyme Inhibitors - pharmacology ; In Vitro Techniques ; Isatis - chemistry ; LC-ESI/MS ; Male ; metabolite ; Microsomes, Liver - chemistry ; Proadifen - pharmacology ; Quinazolines - analysis ; Quinazolines - pharmacokinetics ; rat liver microsome ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Spectrophotometry, Ultraviolet ; Tandem Mass Spectrometry ; tryptanthrin</subject><ispartof>Biological and Pharmaceutical Bulletin, 2007/10/01, Vol.30(10), pp.1991-1995</ispartof><rights>2007 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c690t-28aebb99c2def898b379aab8b6bd530e091063dc00d8304ad9048acd98140c0d3</citedby><cites>FETCH-LOGICAL-c690t-28aebb99c2def898b379aab8b6bd530e091063dc00d8304ad9048acd98140c0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17917280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Sang Kyu</creatorcontrib><creatorcontrib>Kim, Ghee Hwan</creatorcontrib><creatorcontrib>Kim, Dong Hyeon</creatorcontrib><creatorcontrib>Kim, Dong Hyun</creatorcontrib><creatorcontrib>Jahng, Yurngdong</creatorcontrib><creatorcontrib>Jeong, Tae Cheon</creatorcontrib><creatorcontrib>aCollege of Pharmacy</creatorcontrib><creatorcontrib>bBioanalysis and Biotransformation Research Center</creatorcontrib><creatorcontrib>KIST</creatorcontrib><creatorcontrib>Yeungnam University</creatorcontrib><title>Identification of a Tryptanthrin Metabolite in Rat Liver Microsomes by Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry</title><title>Biological & Pharmaceutical Bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses. 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In addition, it was proposed that M1 might be formed by CYP 1A in rat liver microsomes from the experiments with enriched rat liver microsomes.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - analysis</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics</subject><subject>Biotransformation</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Cytochrome P-450 Enzyme Inhibitors</subject><subject>cytochrome P450 (CYP)</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Isatis - chemistry</subject><subject>LC-ESI/MS</subject><subject>Male</subject><subject>metabolite</subject><subject>Microsomes, Liver - chemistry</subject><subject>Proadifen - pharmacology</subject><subject>Quinazolines - analysis</subject><subject>Quinazolines - pharmacokinetics</subject><subject>rat liver microsome</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Spectrophotometry, Ultraviolet</subject><subject>Tandem Mass Spectrometry</subject><subject>tryptanthrin</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNpdkU1vEzEQhlcIRNPCiTuyhMSl2na83g_7CFELkRIhQThb_krjaNfe2g7S8h_4zzgftBKX8djz-J2x36J4h-EGVzW9laO8ITlnDL8oZpjUXdlUuHlZzIBhWra4oRfFZYw7AOigIq-LC9wx3FUUZsWfhTYu2Y1VIlnvkN8ggdZhGpNwaRusQyuThPS9TQbl3XeR0NL-MgGtrAo--sFEJKd89ri3Gs23wQ8i-Ycgxu10e9cblTI1BjGhhXf297FLuRZOmwGtRIzox3hkBpPC9KZ4tRF9NG_P61Xx8_5uPf9aLr99Wcw_LUvVMkhlRYWRkjFVabOhjErSMSEkla3UDQGT3w0t0QpAUwK10AxqKpRmFNegQJOr4uNJdwz-cW9i4oONyvS9cMbvI28paYA1JIMf_gN3fh9cno3jumakJaypMnV9og4_EoPZ8DHYQYSJY-AHj3j2iJOcZ48y_f6suZeD0c_s2ZQM3J-AXM2-9N711pnnzip20vre8yobygEI5DZAuqP8ITS4xVXTZKHPJ6FdTOLBPHUSIVnVm6ep4ByP9_8V1VYEbhz5C5qjvSY</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>Lee, Sang Kyu</creator><creator>Kim, Ghee Hwan</creator><creator>Kim, Dong Hyeon</creator><creator>Kim, Dong Hyun</creator><creator>Jahng, Yurngdong</creator><creator>Jeong, Tae Cheon</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20071001</creationdate><title>Identification of a Tryptanthrin Metabolite in Rat Liver Microsomes by Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry</title><author>Lee, Sang Kyu ; 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To characterize phase I metabolite(s), tryptanthrin was incubated with rat liver microsomes in the presence of NADPH-generating system. One metabolite was identified by liquid chromatography/electrospray ionization-tandem mass spectrometry. M1 could be identified as a metabolite mono-hydroxylated on the aromatic ring of indole moiety from the MS2 spectra of protonated tryptanthrin and M1. The structure of metabolite was confirmed as 8-hydroxytryptanthrin with a chemically synthesized authentic standard. The formation of M1 was NADPH-dependent and was inhibited by SKF-525A, a general CYP-inhibitor, indicating the cytochrome P450 (CYP)-mediated reaction. In addition, it was proposed that M1 might be formed by CYP 1A in rat liver microsomes from the experiments with enriched rat liver microsomes.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>17917280</pmid><doi>10.1248/bpb.30.1991</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0918-6158 |
| ispartof | Biological and Pharmaceutical Bulletin, 2007/10/01, Vol.30(10), pp.1991-1995 |
| issn | 0918-6158 1347-5215 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68350953 |
| source | Free Full-Text Journals in Chemistry |
| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - analysis Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics Biotransformation Chromatography, High Pressure Liquid Cytochrome P-450 Enzyme Inhibitors cytochrome P450 (CYP) Enzyme Inhibitors - pharmacology In Vitro Techniques Isatis - chemistry LC-ESI/MS Male metabolite Microsomes, Liver - chemistry Proadifen - pharmacology Quinazolines - analysis Quinazolines - pharmacokinetics rat liver microsome Rats Rats, Sprague-Dawley Spectrometry, Mass, Electrospray Ionization Spectrophotometry, Ultraviolet Tandem Mass Spectrometry tryptanthrin |
| title | Identification of a Tryptanthrin Metabolite in Rat Liver Microsomes by Liquid Chromatography/Electrospray Ionization-Tandem Mass Spectrometry |
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