Cargando…

Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus

The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Sta...

Descripción completa

Detalles Bibliográficos
Autores principales: Sweeney, Noreena L., Lipker, Lauren, Hanson, Alicia M., Bohl, Chris J., Engel, Katie E., Kalous, Kelsey S., Stemper, Mary E., Sem, Daniel S., Schwan, William R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372984/
https://www.ncbi.nlm.nih.gov/pubmed/28134858
http://dx.doi.org/10.3390/antibiotics6010004
_version_ 1782518732408487936
author Sweeney, Noreena L.
Lipker, Lauren
Hanson, Alicia M.
Bohl, Chris J.
Engel, Katie E.
Kalous, Kelsey S.
Stemper, Mary E.
Sem, Daniel S.
Schwan, William R.
author_facet Sweeney, Noreena L.
Lipker, Lauren
Hanson, Alicia M.
Bohl, Chris J.
Engel, Katie E.
Kalous, Kelsey S.
Stemper, Mary E.
Sem, Daniel S.
Schwan, William R.
author_sort Sweeney, Noreena L.
collection PubMed
description The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Staphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the Mycobacterium tuberculosis thioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability against S. aureus strains, including drug-resistant clinical isolates. The findings support continued development of the pyrazolone compounds as potential anti-S. aureus antibiotics.
format Online
Article
Text
id pubmed-5372984
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-53729842017-04-05 Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus Sweeney, Noreena L. Lipker, Lauren Hanson, Alicia M. Bohl, Chris J. Engel, Katie E. Kalous, Kelsey S. Stemper, Mary E. Sem, Daniel S. Schwan, William R. Antibiotics (Basel) Article The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Staphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the Mycobacterium tuberculosis thioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability against S. aureus strains, including drug-resistant clinical isolates. The findings support continued development of the pyrazolone compounds as potential anti-S. aureus antibiotics. MDPI 2017-01-28 /pmc/articles/PMC5372984/ /pubmed/28134858 http://dx.doi.org/10.3390/antibiotics6010004 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sweeney, Noreena L.
Lipker, Lauren
Hanson, Alicia M.
Bohl, Chris J.
Engel, Katie E.
Kalous, Kelsey S.
Stemper, Mary E.
Sem, Daniel S.
Schwan, William R.
Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus
title Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus
title_full Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus
title_fullStr Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus
title_full_unstemmed Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus
title_short Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus
title_sort docking into mycobacterium tuberculosis thioredoxin reductase protein yields pyrazolone lead molecules for methicillin-resistant staphylococcus aureus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372984/
https://www.ncbi.nlm.nih.gov/pubmed/28134858
http://dx.doi.org/10.3390/antibiotics6010004
work_keys_str_mv AT sweeneynoreenal dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT lipkerlauren dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT hansonaliciam dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT bohlchrisj dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT engelkatiee dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT kalouskelseys dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT stempermarye dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT semdaniels dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus
AT schwanwilliamr dockingintomycobacteriumtuberculosisthioredoxinreductaseproteinyieldspyrazoloneleadmoleculesformethicillinresistantstaphylococcusaureus