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dc.contributor.authorDjaout, K*
dc.contributor.authorSingh, V*
dc.contributor.authorBoum, Y*
dc.contributor.authorKatawera, V*
dc.contributor.authorBecker, H F*
dc.contributor.authorBush, N G*
dc.contributor.authorHearnshaw, S J*
dc.contributor.authorPritchard, J E*
dc.contributor.authorBourbon, P*
dc.contributor.authorMadrid, P B*
dc.contributor.authorMaxwell, A*
dc.contributor.authorMizrahi, V*
dc.contributor.authorMyllykallio, H*
dc.contributor.authorEkins, S*
dc.date.accessioned2016-06-16T22:13:33Zen
dc.date.available2016-06-16T22:13:33Zen
dc.date.issued2016-06-10en
dc.date.submitted2016-06-15en
dc.identifier.citationPredictive modeling targets thymidylate synthase ThyX in Mycobacterium tuberculosis. 2016, 6:27792 Sci Repen
dc.identifier.issn2045-2322en
dc.identifier.pmid27283217en
dc.identifier.doi10.1038/srep27792en
dc.identifier.urihttp://hdl.handle.net/10144/613523en
dc.description.abstractThere is an urgent need to identify new treatments for tuberculosis (TB), a major infectious disease caused by Mycobacterium tuberculosis (Mtb), which results in 1.5 million deaths each year. We have targeted two essential enzymes in this organism that are promising for antibacterial therapy and reported to be inhibited by naphthoquinones. ThyX is an essential thymidylate synthase that is mechanistically and structurally unrelated to the human enzyme. DNA gyrase is a DNA topoisomerase present in bacteria and plants but not animals. The current study set out to understand the structure-activity relationships of these targets in Mtb using a combination of cheminformatics and in vitro screening. Here, we report the identification of new Mtb ThyX inhibitors, 2-chloro-3-(4-methanesulfonylpiperazin-1-yl)-1,4-dihydronaphthalene-1,4-dione) and idebenone, which show modest whole-cell activity and appear to act, at least in part, by targeting ThyX in Mtb.
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsArchived with thanks to Scientific Reportsen
dc.titlePredictive Modeling Targets Thymidylate Synthase ThyX in Mycobacterium Tuberculosisen
dc.identifier.journalScientific Reportsen
refterms.dateFOA2019-03-04T12:47:20Z
html.description.abstractThere is an urgent need to identify new treatments for tuberculosis (TB), a major infectious disease caused by Mycobacterium tuberculosis (Mtb), which results in 1.5 million deaths each year. We have targeted two essential enzymes in this organism that are promising for antibacterial therapy and reported to be inhibited by naphthoquinones. ThyX is an essential thymidylate synthase that is mechanistically and structurally unrelated to the human enzyme. DNA gyrase is a DNA topoisomerase present in bacteria and plants but not animals. The current study set out to understand the structure-activity relationships of these targets in Mtb using a combination of cheminformatics and in vitro screening. Here, we report the identification of new Mtb ThyX inhibitors, 2-chloro-3-(4-methanesulfonylpiperazin-1-yl)-1,4-dihydronaphthalene-1,4-dione) and idebenone, which show modest whole-cell activity and appear to act, at least in part, by targeting ThyX in Mtb.


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