关键词: NorA efflux pump Piperic acid Staphylococcus aureus β-Amino acid γ-Amino acid

Mesh : Amides / chemistry pharmacology Amino Acids / chemistry Anti-Bacterial Agents / chemistry pharmacology Bacterial Proteins / antagonists & inhibitors metabolism Ciprofloxacin / pharmacology Drug Resistance, Bacterial / drug effects Fatty Acids, Unsaturated / chemistry Microbial Sensitivity Tests Multidrug Resistance-Associated Proteins / antagonists & inhibitors metabolism Staphylococcus aureus / drug effects metabolism Structure-Activity Relationship

来  源:   DOI:10.1016/j.bmcl.2016.07.062

Abstract:
A total of eighteen piperic acid (PA) and 4-ethylpiperic acid (EPA) amides (C1-C18) with α-, β- and γ-amino acids were synthesized, characterized and evaluated for their efflux pump inhibitory activity against ciprofloxacin resistant Staphylococcus aureus. The amides were screened against NorA overexpressing S. aureus SA-1199B and wild type S. aureus SA-1199 using ethidium bromide as NorA efflux pump substrate. EPI C6 was found to be most potent and reduced the MIC of ciprofloxacin by 16 fold followed by C18 which showed 4 fold reduction of MIC. Ethidium bromide efflux inhibition and accumulation assay proved these compounds as NorA inhibitors.
摘要:
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