Journal
ARCHIV DER PHARMAZIE
Volume 356, Issue 4, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ardp.202200576
Keywords
amphipathic; antifungal peptides; apoptosis; Cryptococcus neoformans; membrane disruption
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This study synthesizes a series of modified L-histidine-containing peptides that show promising activity against C. neoformans. One of these peptides, 11d, exhibits potent antifungal activity with an IC50 of 3.02 mu g/ml. This peptide is noncytotoxic and nonhemolytic, and synergizes with amphotericin B at subinhibitory concentrations. Mechanistic investigations reveal that 11d disrupts the cell wall and membrane of C. neoformans, leading to cell death through apoptosis. This study demonstrates the antifungal potential of 11d and its rapid onset of action.
Cryptococcus neoformans, an opportunistic fungal pathogen, causes cryptococcosis in immunocompromised persons. A series of modified L-histidines-containing peptides are synthesized that exhibit promising activity against C. neoformans. Analog 11d [L-His(2-adamantyl)-L-Trp-L-His(2-phenyl)-OMe] produced potency with an IC50 of 3.02 mu g/ml (MIC = 5.49 mu g/ml). This peptide is noncytotoxic and nonhaemolytic at the MIC and displays synergistic effects with amphotericin B at subinhibitory concentration. Mechanistic investigation of 11d using microscopic tools indicates cell wall and membrane disruption of C. neoformans, while flow cytometric analysis confirms cell death by apoptosis. This study indicates that 11d exhibits antifungal potential and acts via the rapid onset of action.
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