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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 (CC BY 3.0).
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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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