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Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (III).

  • Author(s): Liu, Yan
  • Haste, Nina M
  • Thienphrapa, Wdee
  • Li, Jerry
  • Nizet, Victor
  • Hensler, Mary
  • Li, Rongshi
  • et al.
Abstract

The marine natural product, marinopyrrole A (1), was previously shown to have significant antibiotic activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Although compound (1) exhibits a significant reduction in MRSA activity in the presence of human serum, we have identified key modifications that partially restore activity. We previously reported our discovery of a chloro-derivative of marinopyrrole A (1a) featuring a 2-4 fold improved minimum inhibitory concentration (MIC) against MRSA, significantly less susceptibility to serum inhibition and rapid and concentration-dependent killing of MRSA. Here, we report a novel fluoro-derivative of marinopyrrole A (1e) showing an improved profile of potency, less susceptibility to serum inhibition, as well as rapid and concentration-dependent killing of MRSA.

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