Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)

Marine Drugs

Yan Liu²  Nina M. Haste³  Wdee Thienphrapa¹  Victor Nizet³  Mary Hensler¹ 

[1] Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA;Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA;Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA;

关键词: marinopyrrole;    asymmetrical marinopyrroles;    MRSA;    antibiotics;    SAR;   

DOI  :  10.3390/md10040953

来源: mdpi

【 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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.