Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus IReport as inadecuate




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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.



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





Author: Yan Liu 1,†, Nina M. Haste 2,†, Wdee Thienphrapa 3, Victor Nizet 2,3, Mary Hensler 3 and Rongshi Li 1,*

Source: http://mdpi.com/



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