Marine Drugs 2012-04-01

Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (I).

Yan Liu, Nina M Haste, Wdee Thienphrapa, Victor Nizet, Mary Hensler, Rongshi Li

文献索引：Mar. Drugs 10(4) , 953-62, (2012)

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摘要

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.