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.author Kumar, Anuradha en_ZA
dc.contributor.author Casey, Allen en_ZA
dc.contributor.author Odingo, Joshua en_ZA
dc.contributor.author Kesicki, Edward A en_ZA
dc.contributor.author Abrahams, Garth en_ZA
dc.contributor.author Vieth, Michal en_ZA
dc.contributor.author Masquelin, Thierry en_ZA
dc.contributor.author Mizrahi, Valerie en_ZA
dc.contributor.author Hipskind, Philip A en_ZA
dc.contributor.author Sherman, David R en_ZA
dc.date.accessioned 2015-11-18T07:06:59Z
dc.date.available 2015-11-18T07:06:59Z
dc.date.issued 2013 en_ZA
dc.identifier.citation Kumar, 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.0072786 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15122
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0072786
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights 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_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Mycobacterium tuberculosis en_ZA
dc.subject.other Library screening en_ZA
dc.subject.other High throughput screening en_ZA
dc.subject.other Enzyme inhibitors en_ZA
dc.subject.other Enzyme assays en_ZA
dc.subject.other Enzymes en_ZA
dc.subject.other Fluorescence en_ZA
dc.subject.other Toxicity en_ZA
dc.title 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 en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2013 Kumar et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Kumar, 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/11427/15122 en_ZA
dc.identifier.chicagocitation Kumar, 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/11427/15122 en_ZA
dc.identifier.vancouvercitation Kumar 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.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


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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. Except where otherwise noted, this item's license is described as 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.