Molecular Umbrellas Modulate the Selective Toxicity of Polyene Macrolide Antifungals
Antifungal polyene macrolide antibiotics Amphotericin B (AmB) and Nystatin (NYS) were conjugated through the ω-amino acid linkers with diwalled “molecular umbrellas” composed of spermidine-linked deoxycholic or cholic acids. The presence of “umbrella” substituents modulated biological properties of the antibiotics, especially their selective toxicity. Some of the AmB-umbrella conjugates demonstrated antifungal in vitro activity comparable to that of the mother antibiotic but diminished mammalian toxicity, especially the hemolytic activity. In contrast, antifungal in vitro activity of NYS-umbrella conjugates was strongly reduced and all these conjugates demonstrated poorer than NYS selective toxicity. No correlation between the aggregation state and hemolytic activity of the novel conjugates was found.
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Andrzej Stanisław Skwarecki, Kornelia Skarbek, Dorota Martynow, Marcin Serocki, Irena Bylińska, Maria Jolanta Milewska, Sławomir Milewski. (2018). Molecular Umbrellas Modulate the Selective Toxicity of Polyene Macrolide Antifungals, 29(4), 1454-1465. https://doi.org/10.1021/acs.bioconjchem.8b00136
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