Molecular Umbrellas Modulate the Selective Toxicity of Polyene Macrolide Antifungals,Bioconjugate Chemistry

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Molecular Umbrellas Modulate the Selective Toxicity of Polyene Macrolide Antifungals
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2018-02-27 00:00:00 , DOI: 10.1021/acs.bioconjchem.8b00136
Andrzej S. Skwarecki , Kornelia Skarbek , Dorota Martynow , Marcin Serocki , Irena Bylińska ₁ , Maria J. Milewska , Sławomir Milewski

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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.

中文翻译：

分子伞调节多烯大环内酯类抗真菌药的选择性毒性。

抗真菌多烯大环内酯类抗生素两性霉素B（AmB）和制霉菌素（NYS）通过ω-氨基酸接头与由亚精胺连接的脱氧胆酸或胆酸组成的双壁“分子伞”结合。“伞状”取代基的存在调节了抗生素的生物学特性，尤其是其选择性毒性。一些AmB伞结合物显示出与母体抗生素相当的体外抗真菌活性，但降低了哺乳动物的毒性，尤其是溶血活性。相反，NYS-伞状结合物的体外抗真菌活性大大降低，并且所有这些结合物均表现出比NYS选择性毒性差的作用。没有发现新型结合物的聚集状态和溶血活性之间的相关性。

更新日期：2018-02-27

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