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dc.contributor.authorBrengel, Christian
dc.contributor.authorThomann, Andreas
dc.contributor.authorSchifrin, Alexander
dc.contributor.authorAllegretta, Giuseppe
dc.contributor.authorKamal, Ahmed A M
dc.contributor.authorHaupenthal, Jörg
dc.contributor.authorSchnorr, Isabell
dc.contributor.authorCho, Sang Hyun
dc.contributor.authorFranzblau, Scott G
dc.contributor.authorEmpting, Martin
dc.contributor.authorEberhard, Jens
dc.contributor.authorHartmann, Rolf W
dc.date.accessioned2018-10-11T14:07:57Z
dc.date.available2018-10-11T14:07:57Z
dc.date.issued2017-10-09
dc.identifier.issn1860-7187
dc.identifier.pmid28815923
dc.identifier.doi10.1002/cmdc.201700363
dc.identifier.urihttp://hdl.handle.net/10033/621515
dc.description.abstractThe development of novel antimycobacterial agents against Mycobacterium tuberculosis (Mtb) is urgently required due to the appearance of multidrug resistance (MDR) combined with complicated long-term treatment. CYP121 was shown to be a promising novel target for inhibition of mycobacterial growth. In this study, we describe the rational discovery of new CYP121 inhibitors by a systematic screening based on biophysical and microbiological methods. The best hits originating from only one structural class gave initial information about molecular motifs required for binding and activity. The initial screening procedure was followed by mode-of-action studies and further biological characterizations. The results demonstrate superior antimycobacterial efficacy and a decreased toxicity profile of our frontrunner compound relative to the reference compound econazole. Due to its low molecular weight, promising biological profile, and physicochemical properties, this compound is an excellent starting point for further rational optimization.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectMycobacterium tuberculosisen_US
dc.subjectanti-infectivesen_US
dc.subjectbiophysicsen_US
dc.subjectinhibitorsen_US
dc.subjectscreeningen_US
dc.titleBiophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials.en_US
dc.typeArticleen_US
dc.contributor.departmentHIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.en_US
refterms.dateFOA2018-10-11T14:07:58Z
dc.source.journaltitleChemMedChem


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