Next Article in Journal
Bioactive Peptides and Depsipeptides with Anticancer Potential: Sources from Marine Animals
Previous Article in Journal
Studies on the Synthesis of Derivatives of Marine-Derived Bostrycin and Their Structure-Activity Relationship against Tumor Cells
Mar. Drugs 2012, 10(4), 953-962; doi:10.3390/md10040953
Article

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

1,†
,
2,†
,
3
,
2,3
,
3
 and
1,*
1 Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA 2 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA 3 Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 12 March 2012 / Revised: 31 March 2012 / Accepted: 18 April 2012 / Published: 24 April 2012
View Full-Text   |   Download PDF [311 KB, uploaded 24 February 2015]   |  

Abstract

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.
Keywords: marinopyrrole; asymmetrical marinopyrroles; MRSA; antibiotics; SAR marinopyrrole; asymmetrical marinopyrroles; MRSA; antibiotics; SAR
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
RIS
MDPI and ACS Style

Liu, Y.; Haste, N.M.; Thienphrapa, W.; Nizet, V.; Hensler, M.; Li, R. Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I). Mar. Drugs 2012, 10, 953-962.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert