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Identification of 2-aminothiazole-4-carboxylate derivatives active against Mycobacterium tuberculosis H37Rv and the beta-ketoacyl-ACP synthase mtFabH
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dc.contributor.author | Al-Balas, Qosay | |
dc.contributor.author | Anthony, Nahoum G. | |
dc.contributor.author | Al-Jaidi, Bilal | |
dc.contributor.author | Alnimr, Amani | |
dc.contributor.author | Abbott, Grainne | |
dc.contributor.author | Brown, Alistair K. | |
dc.contributor.author | Taylor, Rebecca C. | |
dc.contributor.author | Besra, Gurdyal S. | |
dc.contributor.author | McHugh, Timothy D. | |
dc.contributor.author | Gillespie, Stephen H. | |
dc.contributor.author | Johnston, Blair F. | |
dc.contributor.author | Mackay, Simon P. | |
dc.contributor.author | Coxon, Geoffrey D. | |
dc.date.accessioned | 2011-06-28T12:01:30Z | |
dc.date.available | 2011-06-28T12:01:30Z | |
dc.date.issued | 2009-05-19 | |
dc.identifier.citation | Al-Balas , Q , Anthony , N G , Al-Jaidi , B , Alnimr , A , Abbott , G , Brown , A K , Taylor , R C , Besra , G S , McHugh , T D , Gillespie , S H , Johnston , B F , Mackay , S P & Coxon , G D 2009 , ' Identification of 2-aminothiazole-4-carboxylate derivatives active against Mycobacterium tuberculosis H37Rv and the beta-ketoacyl-ACP synthase mtFabH ' , PLoS ONE , vol. 4 , no. 5 , pp. e5617 . https://doi.org/10.1371/journal.pone.0005617 | en |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | PURE: 9672765 | |
dc.identifier.other | PURE UUID: 3d530650-5f74-471b-9fb9-c99bf4118340 | |
dc.identifier.other | WOS: 000266161200017 | |
dc.identifier.other | Scopus: 66149086944 | |
dc.identifier.other | ORCID: /0000-0001-6537-7712/work/39477847 | |
dc.identifier.uri | https://hdl.handle.net/10023/1908 | |
dc.description | The authors have no support or funding to report. | en |
dc.description.abstract | Background: Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings: Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the beta-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 mu g/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)thiazole-4-carboxylate inhibited mtFabH with an IC50 of 0.95 +/- 0.05 mu g/ml (2.43 +/- 0.13 mu M) but was not active against the whole cell organism. Conclusions/Significance: These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents. | |
dc.format.extent | 9 | |
dc.language.iso | eng | |
dc.relation.ispartof | PLoS ONE | en |
dc.rights | © 2009 Al-Balas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en |
dc.subject | QD Chemistry | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | QD | en |
dc.title | Identification of 2-aminothiazole-4-carboxylate derivatives active against Mycobacterium tuberculosis H37Rv and the beta-ketoacyl-ACP synthase mtFabH | en |
dc.type | Journal article | en |
dc.description.version | Publisher PDF | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. Global Health Implementation Group | en |
dc.contributor.institution | University of St Andrews. Infection Group | en |
dc.identifier.doi | https://doi.org/10.1371/journal.pone.0005617 | |
dc.description.status | Peer reviewed | en |
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