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Fungal Glycolipid Hydrolase Inhibitors and Their Effect on Cryptococcus neoformans
- Source :
- Chembiochem : a European journal of chemical biology. 18(3)
- Publication Year :
- 2016
-
Abstract
- Pathogenic fungi kill an estimated 1.3 million people each year. This number is predicted to rise as drug resistance spreads, thus antifungal drugs with novel modes of action are urgently required. Fungal endoglycoceramidase-related proteins 1 and 2 (EGCrP-1 and -2), which hydrolyse glucosylceramide and ergosteryl β-glucoside, respectively, are important for fungal cell growth and have been identified as potential targets for drug development. A library of iminosugar derivatives was screened against EGCrP-1 and -2, and a number of competitive inhibitors with nanomolar affinities were identified. In addition, a mechanism-based inhibitor was shown to form a covalent derivative with EGCrP-2. Nine of the inhibitors were evaluated against Cryptococcus neoformans. Several showed growth inhibitory activity, but only against a C. neoformans strain lacking the outer fungal polysaccharide capsule; this implies that penetration into the cell is a significant handicap for these inhibitors. Pro-drug versions of these inhibitors could address this issue.
- Subjects :
- 0301 basic medicine
Glycoside Hydrolases
Cell
Iminosugar
Drug resistance
Biology
Biochemistry
Microbiology
Fungal Proteins
03 medical and health sciences
Glycolipid
Hydrolase
medicine
Prodrugs
Enzyme Inhibitors
Molecular Biology
Cryptococcus neoformans
Cell growth
Organic Chemistry
biology.organism_classification
Kinetics
030104 developmental biology
medicine.anatomical_structure
Drug development
Molecular Medicine
Rhizopus
Subjects
Details
- ISSN :
- 14397633
- Volume :
- 18
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Chembiochem : a European journal of chemical biology
- Accession number :
- edsair.doi.dedup.....4d9f52e3520ec8c202ecbff3a7db8a37