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Mar. Drugs 2014, 12(5), 2458-2470; doi:10.3390/md12052458
Article

Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (III)

1,2,3,†
, 4,5,†
, 5
, 3
, 4,5
, 5
 and 1,2,3,6,*
1 Department of Pharmaceutical Sciences, Center for Drug Discovery, College of Pharmacy, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA 2 Cancer Genes and Molecular Regulation Program, Buffett Cancer Center, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA 3 Department of Drug Discovery, Chemical Biology & Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA 4 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA 5 Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA 6 Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs, Tampa, FL 33612, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 10 February 2014 / Revised: 21 March 2014 / Accepted: 24 March 2014 / Published: 30 April 2014
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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.
Keywords: antibiotics; non-symmetrical marinopyrroles; MRSA; SAR antibiotics; non-symmetrical marinopyrroles; MRSA; SAR
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Liu, Y.; Haste, N.M.; Thienphrapa, W.; Li, J.; Nizet, V.; Hensler, M.; Li, R. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (III). Mar. Drugs 2014, 12, 2458-2470.

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