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Mar. Drugs 2012, 10(4), 953-962; doi:10.3390/md10040953

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

1
Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
2
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA
3
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 12 March 2012 / Revised: 31 March 2012 / Accepted: 18 April 2012 / Published: 24 April 2012
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Abstract

Infections caused by drug-resistant pathogens are on the rise. The ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA) strains exemplifies the urgent need for new antibiotics. The marine natural product, marinopyrrole A, was previously shown to have potent antibiotic activity against Gram-positive pathogens, including MRSA. However, its minimum inhibitory concentration (MIC) against MRSA was increased by >500 fold in the presence of 20% human serum, thus greatly limiting therapeutic potential. Here we report our discovery of a novel derivative of marinopyrrole A, designated 1a, featuring a 2–4 fold improved MIC against MRSA and significantly less susceptibility to serum inhibition. Importantly, compound 1a displayed rapid and concentration-dependent killing of MRSA. Compared to the natural product counterpart, compound 1a provides an important natural product based scaffold for further Structure Activity Relationship (SAR) and optimization. View Full-Text
Keywords: marinopyrrole; asymmetrical marinopyrroles; MRSA; antibiotics; SAR marinopyrrole; asymmetrical marinopyrroles; MRSA; antibiotics; SAR
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Liu, Y.; Haste, N.M.; Thienphrapa, W.; Nizet, V.; Hensler, M.; Li, R. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I). Mar. Drugs 2012, 10, 953-962.

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