| Metabolism of a sulfur-containing heteroarotionoid antitumor agent, SHetA2, using liquid chromatography/tandem mass spectrometry. | |
| | |
MedLine Citation:
|
PMID: 18837006 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
SHetA2 {[(4-nitrophenyl)amino][2,2,4,4-tetramethylthiochroman-6-yl)amino]methanethione], NSC 726189}, a sulfur-containing heteroarotinoid, selectively inhibits cancer cell growth and induces apoptosis without activation of nuclear retinoic acid receptors (RARs). The objective of this study was to investigate its in vitro metabolism in rat and human liver microsomes and in vivo metabolism in the mouse and rat using liquid chromatography-ultraviolet/multi-stage mass spectrometry (LC-UV/MS(n)) on an ion-trap mass spectrometer coupled with a photo-diode array (PDA) detector. In vitro, in the absence of glutathione (GSH), oxidation of the four aliphatic methyl groups of SHetA2 yielded one mono-, two di-, and one tri-hydroxylated SHetA2 metabolites, which were identified based on their UV and multi-stage mass spectra. In the presence of GSH, in addition to these primary oxidative metabolites, four GSH adducts of SHetA2 and a novel rare form thioether GSH adduct was detected and characterized. In vivo, the monohydroxylated SHetA2 metabolites were also detected in mouse and rat plasma and two GSH adducts were detected in rat liver following intravenous (i.v.) bolus administration of SHetA2 at 40 mg/kg. |
| | |
Authors:
|
Zhongfa Liu; Yilong Zhang; Yousheng Frank Hua; Joseph M Covey; Doris M Benbrook; Kenneth K Chan |
Related Documents
:
|
9022286 - Purification and characterization of glutathione s-transferases of rat uterus. 6229626 - Differences in the effects of selenite and biological selenium on the chemical form and... 17386 - Properties of glutathione release observed during reduction of organic hydroperoxide, d... 1981536 - Metabolism of hexafluoropropene. evidence for bioactivation by glutathione conjugate fo... 6593726 - Target polypeptide of a carcinogen is associated with normal mitosis and carcinogen-ind... 21372616 - Effects of bevacizumab (avastin®) on the electroretinogram of isolated rat retina. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Rapid communications in mass spectrometry : RCM Volume: 22 ISSN: 0951-4198 ISO Abbreviation: Rapid Commun. Mass Spectrom. Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-10-15 Completed Date: 2008-12-18 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8802365 Medline TA: Rapid Commun Mass Spectrom Country: England |
Other Details:
|
Languages: eng Pagination: 3371-81 Citation Subset: IM |
Affiliation:
|
College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antineoplastic Agents / blood, metabolism* Chromans / blood, chemistry, metabolism* Chromatography, Liquid / methods* Glutathione / chemistry, metabolism Humans Male Metabolic Networks and Pathways* Microsomes, Liver / metabolism Rats Rats, Sprague-Dawley Sulfur / chemistry Tandem Mass Spectrometry / methods* Thiones / blood, chemistry, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
N01-CM-07019/CM/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/(((4-nitrophenyl)amino)(2,2,4,4-tetramethyl thiochroman-6-yl)amino) methane-1-thione; 0/Antineoplastic Agents; 0/Chromans; 0/Thiones; 70-18-8/Glutathione; 7704-34-9/Sulfur |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reducing glycerophosphocholine lipid matrix interference effects in biological fluid assays by using...
Next Document: Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney...