%0 Journal Article
%T Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)
%A Yan Liu
%A Nina M. Haste
%A Wdee Thienphrapa
%A Victor Nizet
%A Mary Hensler
%A Rongshi Li
%J Marine Drugs
%D 2012
%I MDPI AG
%R 10.3390/md10040953
%X 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¨C4 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.
%K marinopyrrole
%K asymmetrical marinopyrroles
%K MRSA
%K antibiotics
%K SAR
%U http://www.mdpi.com/1660-3397/10/4/953