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.
Andrzej 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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