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Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents
This is the first report of 5-styryl-oxathiazol-2-ones as inhibitors of the Mycobacterium tuberculosis (Mtb) proteasome. As part of the study, the structure–activity relationship of oxathiazolones as Mtb proteasome inhibitors has been investigated. Furthermore, the prepared compounds displayed a goo...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522185/ https://www.ncbi.nlm.nih.gov/pubmed/26246997 http://dx.doi.org/10.1002/open.201500001 |
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author | Russo, Francesco Gising, Johan Åkerbladh, Linda Roos, Annette K Naworyta, Agata Mowbray, Sherry L Sokolowski, Anders Henderson, Ian Alling, Torey Bailey, Mai A Files, Megan Parish, Tanya Karlén, Anders Larhed, Mats |
author_facet | Russo, Francesco Gising, Johan Åkerbladh, Linda Roos, Annette K Naworyta, Agata Mowbray, Sherry L Sokolowski, Anders Henderson, Ian Alling, Torey Bailey, Mai A Files, Megan Parish, Tanya Karlén, Anders Larhed, Mats |
author_sort | Russo, Francesco |
collection | PubMed |
description | This is the first report of 5-styryl-oxathiazol-2-ones as inhibitors of the Mycobacterium tuberculosis (Mtb) proteasome. As part of the study, the structure–activity relationship of oxathiazolones as Mtb proteasome inhibitors has been investigated. Furthermore, the prepared compounds displayed a good selectivity profile for Mtb compared to the human proteasome. The 5-styryl-oxathiazol-2-one inhibitors identified showed little activity against replicating Mtb, but were rapidly bactericidal against nonreplicating bacteria. (E)-5-(4-Chlorostyryl)-1,3,4-oxathiazol-2-one) was most effective, reducing the colony-forming units (CFU)/mL below the detection limit in only seven days at all concentrations tested. The results suggest that this new class of Mtb proteasome inhibitors has the potential to be further developed into novel antitubercular agents for synergistic combination therapies with existing drugs. |
format | Online Article Text |
id | pubmed-4522185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45221852015-08-05 Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents Russo, Francesco Gising, Johan Åkerbladh, Linda Roos, Annette K Naworyta, Agata Mowbray, Sherry L Sokolowski, Anders Henderson, Ian Alling, Torey Bailey, Mai A Files, Megan Parish, Tanya Karlén, Anders Larhed, Mats ChemistryOpen Full Papers This is the first report of 5-styryl-oxathiazol-2-ones as inhibitors of the Mycobacterium tuberculosis (Mtb) proteasome. As part of the study, the structure–activity relationship of oxathiazolones as Mtb proteasome inhibitors has been investigated. Furthermore, the prepared compounds displayed a good selectivity profile for Mtb compared to the human proteasome. The 5-styryl-oxathiazol-2-one inhibitors identified showed little activity against replicating Mtb, but were rapidly bactericidal against nonreplicating bacteria. (E)-5-(4-Chlorostyryl)-1,3,4-oxathiazol-2-one) was most effective, reducing the colony-forming units (CFU)/mL below the detection limit in only seven days at all concentrations tested. The results suggest that this new class of Mtb proteasome inhibitors has the potential to be further developed into novel antitubercular agents for synergistic combination therapies with existing drugs. John Wiley & Sons, Ltd 2015-06 2015-04-17 /pmc/articles/PMC4522185/ /pubmed/26246997 http://dx.doi.org/10.1002/open.201500001 Text en © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Full Papers Russo, Francesco Gising, Johan Åkerbladh, Linda Roos, Annette K Naworyta, Agata Mowbray, Sherry L Sokolowski, Anders Henderson, Ian Alling, Torey Bailey, Mai A Files, Megan Parish, Tanya Karlén, Anders Larhed, Mats Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents |
title | Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents |
title_full | Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents |
title_fullStr | Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents |
title_full_unstemmed | Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents |
title_short | Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents |
title_sort | optimization and evaluation of 5-styryl-oxathiazol-2-one mycobacterium tuberculosis proteasome inhibitors as potential antitubercular agents |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522185/ https://www.ncbi.nlm.nih.gov/pubmed/26246997 http://dx.doi.org/10.1002/open.201500001 |
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