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

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; in revised form: 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.
Keywords: marinopyrrole; asymmetrical marinopyrroles; MRSA; antibiotics; SAR

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MDPI and ACS Style

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.

AMA Style

Liu Y, Haste NM, Thienphrapa W, Nizet V, Hensler M, Li R. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I). Marine Drugs. 2012; 10(4):953-962.

Chicago/Turabian Style

Liu, Yan; Haste, Nina M.; Thienphrapa, Wdee; Nizet, Victor; Hensler, Mary; Li, Rongshi. 2012. "Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)." Mar. Drugs 10, no. 4: 953-962.

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