Kribellosides, novel RNA 5'-triphosphatase inhibitors from the rare actinomycete Kribbella sp. MI481-42F6.
J Antibiot (Tokyo)
; 70(5): 582-589, 2017 May.
Article
em En
| MEDLINE
| ID: mdl-28074052
ABSTRACT
Yeast capping enzymes differ greatly from those of mammalian, both structurally and mechanistically. Yeast-type capping enzyme repressors are therefore candidate antifungal drugs. The 5'-guanine-N7 cap structure of mRNAs are an essential feature of all eukaryotic organisms examined to date and is the first co-transcriptional modification of cellular pre-messenger RNA. Inhibitors of the RNA 5'-triphosphatase in yeast are likely to show fungicidal effects against pathogenic yeast such as Candida. We discovered a new RNA 5'-triphosphatase inhibitor, designated as the kribellosides, by screening metabolites from actinomycetes. Kribellosides belong to the alkyl glyceryl ethers. These novel compounds inhibit the activity of Cet1p (RNA 5'-triphosphatase) from Saccharomyces cerevisiae in vitro with IC50s of 5-8 µM and show antifungal activity with MICs ranging from 3.12 to 100 µg ml-1 against S. cerevisiae.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Actinobacteria
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Hidrolases Anidrido Ácido
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Inibidores Enzimáticos
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Antifúngicos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article