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

Marine Drugs

Yan Liu¹  Nina M. Haste³  Wdee Thienphrapa⁴  Jerry Li²  Victor Nizet³  Mary Hensler⁴ 

[1] Department of Pharmaceutical Sciences, Center for Drug Discovery, College of Pharmacy, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA; E-Mail:;Department of Drug Discovery, Chemical Biology & Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA; E-Mail:;Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA; E-Mails:;Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; E-Mails:

关键词: antibiotics;    non-symmetrical marinopyrroles;    MRSA;    SAR;   

DOI  :  10.3390/md12052458

来源: mdpi

【 摘 要 】

The marine natural product, marinopyrrole A (1), was previously shown to have significant antibiotic activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Although compound (1) exhibits a significant reduction in MRSA activity in the presence of human serum, we have identified key modifications that partially restore activity. We previously reported our discovery of a chloro-derivative of marinopyrrole A (1a) featuring a 2–4 fold improved minimum inhibitory concentration (MIC) against MRSA, significantly less susceptibility to serum inhibition and rapid and concentration-dependent killing of MRSA. Here, we report a novel fluoro-derivative of marinopyrrole A (1e) showing an improved profile of potency, less susceptibility to serum inhibition, as well as rapid and concentration-dependent killing of MRSA.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.