title: Identification of a tryptanthrin metabolite in rat liver microsomes by liquid chromatography/electrospray ionization-tandem mass spectrometry.
abstract: 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 MS(2) 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Lee
authors.forename: Ghee Hwan
authors.initials: GH
authors.lastname: Kim
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Kim
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Yurngdong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis* / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D031219:Isatis / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry*; D011335:Proadifen / Q000494:pharmacology; D011799:Quinazolines / Q000032:analysis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D011799:Quinazolines; C046243:tryptanthrine; D011335:Proadifen