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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Synergistic Fungicidal Activities of Amphotericin B and N-Methyl-N'-dodecylguanidine: A Constituent of Polyol Macrolide Antibiotic Niphimycin
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Synergistic Fungicidal Activities of Amphotericin B and N-Methyl-N'-dodecylguanidine: A Constituent of Polyol Macrolide Antibiotic Niphimycin

机译：两性霉素B和N-甲基-N“-十二烷基胍的协同杀真菌活性：多元醇大环内酯类抗生素烟霉素的成分。

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摘要

The synergy between the alkylguanidinium chain of niphimycin (NM),a polyol macrolide antibiotic,and polyene macrolide amphotericin B (AmB) without such an alkyl side chain was examined using N-methyl-N"-alkylguanidines as its synthetic analogs.Among the analogs,N-methyl-N"-dodecylguanidine (MCl2) most strongly inhibited the growth of Saccharomyces cerevisiae cells and those of other fungal strains in synergy with AmB.MCl2 itself was not lethal but the analog could be a cause of a rapid cell death progression of yeast cells in the presence of AmB at a nonlethal concentration.Their combined actions resulted in the generation of NM-like fungicidal activity that depended on plasma membrane disability and cellular reactive oxygen species production.We also found an aberrant vacuolar morphogenesis and an associated vacuolar membrane disability in cells treated simultaneously with MCl2 and AmB,as in the case of NM-treated cells.These findings support the idea that the alkylguanidinium chain plays a major role in the fungicidal activity of NM in cooperation with the polyol lactone ring as its enhancer.
机译：使用N-甲基-N“-烷基胍作为其合成类似物，研究了多酚大环内酯抗生素尼福霉素（NM）的烷基胍链与不具有烷基侧链的多烯大环内酯两性霉素B（AmB）之间的协同作用。 ，N-甲基-N“-十二烷基胍（MCl2）与AmB协同作用最强地抑制了酿酒酵母细胞和其他真菌菌株的生长。MCl2本身没有致死性，但类似物可能是细胞快速死亡的原因。在非致死浓度的AmB存在下酵母细胞的分解，它们的联合作用导致了类似NM的杀真菌活性的产生，这取决于质膜的失能和细胞活性氧的产生。我们还发现了异常的液泡形态发生和相关的液泡与NM处理的细胞一样，在同时用MCl2和AmB处理的细胞中，细胞膜功能失调。这些发现支持了烷基胍链p与多元醇内酯环作为促进剂配合使用，在NM的杀菌活性中起主要作用。

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