Synthesis and Bioactivities of Kanamycin B-Derived Cationic Amphiphiles.
作者： Keith D. Green , Sylvie Garneau-Tsodikova
DOI: 10.1021/ACS.JMEDCHEM.5B01375
关键词:
摘要: Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on AG backbone, interesting antibacterial and antifungal agents with a novel mechanism action developed. Herein, we report design synthesis seven kanamycin B (KANB) derivatives. Their activities, along resistance/enzymatic, hemolytic, cytotoxicity assays were also studied. Two these compounds, C12 C14 aliphatic chain attached at 6″-position KANB through thioether linkage, exhibited good activity, poorer substrates than for several AG-modifying enzymes, could delay development resistance in bacteria fungi. Also, they both relatively less hemolytic known membrane targeting antibiotic gramicidin agent amphotericin not toxic their MIC values. oxidation sulfones was demonstrated no effect activities. Moreover, acted synergistically posaconazole, an azole currently used treatment human fungal infections.
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