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Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments
Drug-resistant Staphylococcus aureus is a continuing public health concern, both in the hospital and community settings. Antibacterial compounds that possess novel structural scaffolds and are effective against multiple S. aureus strains, including current drug-resistant ones, are needed. Previously...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397459/ https://www.ncbi.nlm.nih.gov/pubmed/22822360 http://dx.doi.org/10.3390/md10051103 |
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author | Keffer, Jessica L. Hammill, Jared T. Lloyd, John R. Plaza, Alberto Wipf, Peter Bewley, Carole A. |
author_facet | Keffer, Jessica L. Hammill, Jared T. Lloyd, John R. Plaza, Alberto Wipf, Peter Bewley, Carole A. |
author_sort | Keffer, Jessica L. |
collection | PubMed |
description | Drug-resistant Staphylococcus aureus is a continuing public health concern, both in the hospital and community settings. Antibacterial compounds that possess novel structural scaffolds and are effective against multiple S. aureus strains, including current drug-resistant ones, are needed. Previously, we have described the chrysophaentins, a family of bisdiarylbutene macrocycles from the chrysophyte alga Chrysophaeum taylori that inhibit the growth of S. aureus and methicillin-resistant S. aureus (MRSA). In this study we have analyzed the geographic variability of chrysophaentin production in C. taylori located at different sites on the island of St. John, U.S. Virgin Islands, and identified two new linear chrysophaentin analogs, E2 and E3. In addition, we have expanded the structure activity relationship through synthesis of fragments comprising conserved portions of the chrysophaentins, and determined the antimicrobial activity of natural chrysophaentins and their synthetic analogs against five diverse S. aureus strains. We find that the chrysophaentins show similar activity against all S. aureus strains, regardless of their drug sensitivity profiles. The synthetic chrysophaentin fragments indeed mimic the natural compounds in their spectrum of antibacterial activity, and therefore represent logical starting points for future medicinal chemistry studies of the natural products and their analogs. |
format | Online Article Text |
id | pubmed-3397459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-33974592012-07-20 Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments Keffer, Jessica L. Hammill, Jared T. Lloyd, John R. Plaza, Alberto Wipf, Peter Bewley, Carole A. Mar Drugs Article Drug-resistant Staphylococcus aureus is a continuing public health concern, both in the hospital and community settings. Antibacterial compounds that possess novel structural scaffolds and are effective against multiple S. aureus strains, including current drug-resistant ones, are needed. Previously, we have described the chrysophaentins, a family of bisdiarylbutene macrocycles from the chrysophyte alga Chrysophaeum taylori that inhibit the growth of S. aureus and methicillin-resistant S. aureus (MRSA). In this study we have analyzed the geographic variability of chrysophaentin production in C. taylori located at different sites on the island of St. John, U.S. Virgin Islands, and identified two new linear chrysophaentin analogs, E2 and E3. In addition, we have expanded the structure activity relationship through synthesis of fragments comprising conserved portions of the chrysophaentins, and determined the antimicrobial activity of natural chrysophaentins and their synthetic analogs against five diverse S. aureus strains. We find that the chrysophaentins show similar activity against all S. aureus strains, regardless of their drug sensitivity profiles. The synthetic chrysophaentin fragments indeed mimic the natural compounds in their spectrum of antibacterial activity, and therefore represent logical starting points for future medicinal chemistry studies of the natural products and their analogs. MDPI 2012-05-22 /pmc/articles/PMC3397459/ /pubmed/22822360 http://dx.doi.org/10.3390/md10051103 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 Keffer, Jessica L. Hammill, Jared T. Lloyd, John R. Plaza, Alberto Wipf, Peter Bewley, Carole A. Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments |
title | Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments |
title_full | Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments |
title_fullStr | Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments |
title_full_unstemmed | Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments |
title_short | Geographic Variability and Anti-Staphylococcal Activity of the Chrysophaentins and Their Synthetic Fragments |
title_sort | geographic variability and anti-staphylococcal activity of the chrysophaentins and their synthetic fragments |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397459/ https://www.ncbi.nlm.nih.gov/pubmed/22822360 http://dx.doi.org/10.3390/md10051103 |
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