Source:http://linkedlifedata.com/resource/pubmed/id/15892174
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2005-6-23
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pubmed:abstractText |
The cyclic depsipeptide aplidine is a new anti-cancer drug of marine origin. Four metabolites of this compound were found after incubation with pooled human microsomes using gradient high-performance liquid chromatography with ultraviolet detection. After chromatographic isolation, the metabolites have been identified using nano-electrospray triple quadrupole mass spectrometry. A highly specific sodium-ion interaction with the cyclic structure opens the depsipeptide ring, and cleavage of the amino acid residues gives sequence information when activated by collision-induced dissociation in the second quadrupole. The aplidine molecule could undergo the following metabolic reactions: hydroxylation at the isopropyl group (metabolites apli-h 1 and apli-h 2); C-dealkylation at the N(Me)-leucine group (metabolite apli-da); hydroxylation at the isopropyl group and C-dealkylation at the N(Me)-leucine group (metabolite apli-da/h), and C-demethylation at the threonine group (metabolite apli-dm). The identification of these metabolites formed in vitro may greatly aid the elucidation of the metabolic pathways of aplidine in humans.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1076-5174
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
821-31
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pubmed:meshHeading |
pubmed-meshheading:15892174-Antineoplastic Agents,
pubmed-meshheading:15892174-Chromatography, High Pressure Liquid,
pubmed-meshheading:15892174-Depsipeptides,
pubmed-meshheading:15892174-Female,
pubmed-meshheading:15892174-Humans,
pubmed-meshheading:15892174-Male,
pubmed-meshheading:15892174-Microchemistry,
pubmed-meshheading:15892174-Microsomes, Liver,
pubmed-meshheading:15892174-Molecular Structure,
pubmed-meshheading:15892174-Nanotechnology,
pubmed-meshheading:15892174-Spectrometry, Mass, Electrospray Ionization
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pubmed:year |
2005
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pubmed:articleTitle |
Structure elucidation of aplidine metabolites formed in vitro by human liver microsomes using triple quadrupole mass spectrometry.
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pubmed:affiliation |
Utrecht University, Faculty of Pharmaceutical Sciences, Department of Biomedical Analysis, Division of Drug Toxicology, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
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pubmed:publicationType |
Journal Article
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