Molecular umbrellas modulate the selective toxicity of polyene macrolide antifungals
Andrzej S. Skwarecki , Kornelia Skarbek , Dorota Martynow , Marcin Serocki , Irena Bylińska , Maria J. Milewska , Sławomir Milewski
AbstractAntifungal polyene macrolide antibiotics Amphotericin B (AmB) and Nystatin (NYS) were conjugated through the omega-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.
|Journal series||Bioconjugate Chemistry, ISSN 1043-1802|
|Publication size in sheets||0.55|
|Score|| = 35.0, 27-06-2018, ArticleFromJournal|
= 40.0, 27-06-2018, ArticleFromJournal
|Publication indicators||: 2016 = 4.818 (2) - 2016=4.574 (5)|
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