Linked Life Data

6141902

Source:http://linkedlifedata.com/resource/pubmed/id/6141902

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1984-4-11
pubmed:abstractText
Nine ether-extractable metabolites of cyclosporine were isolated from urine of dog and man and from rat bile and feces and purified by preparative HPLC and TLC. Structural assignments were mainly based on spectroscopic data (1H NMR, 13C NMR, MS) and the results of the amino acid analysis after hydrolysis with hydrochloric acid. All the identified metabolites retained the intact cyclic oligopeptide structure of the parent drug. Structural modifications originated from enzymatic oxidation at specific sites of the peptide subunits. Transformation processes principally involved hydroxylation at the terminal carbon atom (eta-position) of the C9-amino acid 1 and the gamma-position of the N-methylleucines 4, 6, and 9, as well as N-demethylation of the N-methylleucine 4. Regioisomeric monohydroxylated cyclosporines (metabolites 1, and 17) and N-demethylcyclosporine (metabolite 21) were the primary metabolites resulting from hydroxylation of the C9-amino-acid 1 and the N-methylleucine 9, and from N-demethylation of the N-methylleucine 4. Dihydroxylated derivatives of cyclosporine (metabolites 8, 10, and 16) were generated by further oxidation of metabolite 1 on one of the other N-methylleucines (4 or 6) or on the C9-amino acid 1, or of metabolite 17 on the N-methylleucine 9. More extensive modifications were observed for metabolite 9, a dihydroxy-N-demethylcyclosporine, which could have been formed from the dihydroxy derivative 16 by N-demethylation or from the N-demethylcyclosporine 21 by dihydroxylation. Metabolite 18 differed from 17 (monohydroxycyclosporine) by the presence of a cyclic ether moiety, formally derived by intramolecular addition of the beta-hydroxyl group to the double bond of the C9-amino acid 1.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Disposition of cyclosporine in several animal species and man. I. Structural elucidation of its metabolites.
pubmed:publicationType
Journal Article