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

Abstract

Antifungal 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.
Author Andrzej S. Skwarecki
Andrzej S. Skwarecki,,
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, Kornelia Skarbek
Kornelia Skarbek,,
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, Dorota Martynow
Dorota Martynow,,
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, Marcin Serocki
Marcin Serocki,,
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, Irena Bylińska PFotobiofizyki
Irena Bylińska,,
- Laboratory of Photobiophysics
, Maria J. Milewska
Maria J. Milewska,,
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, Sławomir Milewski
Sławomir Milewski,,
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Journal seriesBioconjugate Chemistry, ISSN 1043-1802
Issue year2018
Vol29
No4
Pages1454-1465
Publication size in sheets0.55
DOIDOI:10.1021/acs.bioconjchem.8b00136
URL https://pubs.acs.org/doi/ipdf/10.1021/acs.bioconjchem.8b00136
Languageen angielski
Score (nominal)40
ScoreMinisterial score = 35.0, 27-06-2018, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, 27-06-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 4.818 (2) - 2016=4.574 (5)
Citation count*0
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