Linked Life Data

2090934

Source:http://linkedlifedata.com/resource/pubmed/id/2090934

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7-8
pubmed:dateCreated
1991-6-4
pubmed:abstractText
The N-1-substituted triazole antifungal, saperconazole, is a potent inhibitor of ergosterol synthesis in Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes. Fifty % inhibition is already achieved at nanomolar concentrations. The saperconazole-induced inhibition of ergosterol synthesis coincides with an accumulation of 14-methylated sterols, such as 24-methylenedihydrolanosterol, lanosterol, obtusifoliol, 14 alpha-methylfecosterol, 14 alpha-methylergosta-8,24(28)-dien-3 beta-6 alpha-diol and 14 alpha-methylergosta-5,7,22,24(28)-tetraenol. This indicates that saperconazole interferes with the cytochrome P-450 (P-450)-dependent 14 alpha-demethylation of lanosterol and/or 24-methylenedihydrolanosterol. Saperconazole forms stable drug-P-450-complexes by binding via its free triazole nitrogen to the heme iron and via its N-1 substituent to the apoprotein moiety. The triazole derivative is a highly selective inhibitor of the 14 alpha-demethylase in fungal cells. It is a poor inhibitor of the 14 alpha-demethylation of lanosterol in rat and human liver cells. Saperconazole is, at concentrations as high as 10 microM, devoid of effects on the P-450-dependent cholesterol side-chain cleavage and 11 beta-hydroxylase, 17,20-lyase,21-hydroxylase and aromatase. Saperconazole does not interfere with the 2 alpha, 6 alpha-, 6 beta- and 7 alpha-hydroxylations of testosterone in microsomes from male rat liver. At high concentrations (greater than 5 microM) an inhibition of the 16 beta-hydroxylations is seen.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0933-7407
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
335-52
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:articleTitle
Saperconazole: a selective inhibitor of the cytochrome P-450-dependent ergosterol synthesis in Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes.
pubmed:affiliation
Janssen Research Foundation, Beerse, Belgium.
pubmed:publicationType
Journal Article