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

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 agains...

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Autores principales: Liu, Yan, Haste, Nina M., Thienphrapa, Wdee, Nizet, Victor, Hensler, Mary, Li, Rongshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366685/
https://www.ncbi.nlm.nih.gov/pubmed/22690153
http://dx.doi.org/10.3390/md10040953
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author Liu, Yan
Haste, Nina M.
Thienphrapa, Wdee
Nizet, Victor
Hensler, Mary
Li, Rongshi
author_facet Liu, Yan
Haste, Nina M.
Thienphrapa, Wdee
Nizet, Victor
Hensler, Mary
Li, Rongshi
author_sort Liu, Yan
collection PubMed
description 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.
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spelling pubmed-33666852012-06-11 Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I) Liu, Yan Haste, Nina M. Thienphrapa, Wdee Nizet, Victor Hensler, Mary Li, Rongshi Mar Drugs Article 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. MDPI 2012-04-24 /pmc/articles/PMC3366685/ /pubmed/22690153 http://dx.doi.org/10.3390/md10040953 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Liu, Yan
Haste, Nina M.
Thienphrapa, Wdee
Nizet, Victor
Hensler, Mary
Li, Rongshi
Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)
title Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)
title_full Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)
title_fullStr Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)
title_full_unstemmed Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)
title_short Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)
title_sort marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant staphylococcus aureus (i)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366685/
https://www.ncbi.nlm.nih.gov/pubmed/22690153
http://dx.doi.org/10.3390/md10040953
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