A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis

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dc.contributor.authorKumar, Anuradhaen_ZA
dc.contributor.authorCasey, Allenen_ZA
dc.contributor.authorOdingo, Joshuaen_ZA
dc.contributor.authorKesicki, Edward Aen_ZA
dc.contributor.authorAbrahams, Garthen_ZA
dc.contributor.authorVieth, Michalen_ZA
dc.contributor.authorMasquelin, Thierryen_ZA
dc.contributor.authorMizrahi, Valerieen_ZA
dc.contributor.authorHipskind, Philip Aen_ZA
dc.contributor.authorSherman, David Ren_ZA
dc.date.accessioned2015-11-18T07:06:59Z
dc.date.available2015-11-18T07:06:59Z
dc.date.issued2013en_ZA
dc.description.abstractThe enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis . It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.en_ZA
dc.identifier.apacitationKumar, A., Casey, A., Odingo, J., Kesicki, E. A., Abrahams, G., Vieth, M., ... Sherman, D. R. (2013). A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis. <i>PLoS One</i>, http://hdl.handle.net/11427/15122en_ZA
dc.identifier.chicagocitationKumar, Anuradha, Allen Casey, Joshua Odingo, Edward A Kesicki, Garth Abrahams, Michal Vieth, Thierry Masquelin, Valerie Mizrahi, Philip A Hipskind, and David R Sherman "A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/15122en_ZA
dc.identifier.citationKumar, A., Casey, A., Odingo, J., Kesicki, E. A., Abrahams, G., Vieth, M., ... & Parish, T. (2012). A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis. PloS one, 8(11), e72786. doi:10.1371/journal.pone.0072786en_ZA
dc.identifier.ris TY - Journal Article AU - Kumar, Anuradha AU - Casey, Allen AU - Odingo, Joshua AU - Kesicki, Edward A AU - Abrahams, Garth AU - Vieth, Michal AU - Masquelin, Thierry AU - Mizrahi, Valerie AU - Hipskind, Philip A AU - Sherman, David R AB - The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis . It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0072786 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis TI - A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis UR - http://hdl.handle.net/11427/15122 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15122
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0072786
dc.identifier.vancouvercitationKumar A, Casey A, Odingo J, Kesicki EA, Abrahams G, Vieth M, et al. A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis. PLoS One. 2013; http://hdl.handle.net/11427/15122.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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_ZA
dc.rights.holder© 2013 Kumar et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherLibrary screeningen_ZA
dc.subject.otherHigh throughput screeningen_ZA
dc.subject.otherEnzyme inhibitorsen_ZA
dc.subject.otherEnzyme assaysen_ZA
dc.subject.otherEnzymesen_ZA
dc.subject.otherFluorescenceen_ZA
dc.subject.otherToxicityen_ZA
dc.titleA high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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