Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Marine drugs, 2012-04, Vol.10 (4), p.953-962

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.