<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Flipo, Marion</style></author><author><style face="normal" font="default" size="100%">Frita, Rosangela</style></author><author><style face="normal" font="default" size="100%">Marilyne Bourotte</style></author><author><style face="normal" font="default" size="100%">Maria S Martínez-Martínez</style></author><author><style face="normal" font="default" size="100%">Markus Boesche</style></author><author><style face="normal" font="default" size="100%">Gary W Boyle</style></author><author><style face="normal" font="default" size="100%">Geo Derimanov</style></author><author><style face="normal" font="default" size="100%">Gerard Drewes</style></author><author><style face="normal" font="default" size="100%">Pablo Gamallo</style></author><author><style face="normal" font="default" size="100%">Sonja Ghidelli-Disse</style></author><author><style face="normal" font="default" size="100%">Stephanie Gresham</style></author><author><style face="normal" font="default" size="100%">Elena Jiménez</style></author><author><style face="normal" font="default" size="100%">Jaime de Mercado</style></author><author><style face="normal" font="default" size="100%">Esther Pérez-Herrán</style></author><author><style face="normal" font="default" size="100%">Esther Porras-De Francisco</style></author><author><style face="normal" font="default" size="100%">Joaquín Rullas</style></author><author><style face="normal" font="default" size="100%">Patricia Casado</style></author><author><style face="normal" font="default" size="100%">Florence Leroux</style></author><author><style face="normal" font="default" size="100%">Catherine Piveteau</style></author><author><style face="normal" font="default" size="100%">Kiass, Mehdi</style></author><author><style face="normal" font="default" size="100%">Vanessa Mathys</style></author><author><style face="normal" font="default" size="100%">Karine Soetaert</style></author><author><style face="normal" font="default" size="100%">Véronique Megalizzi</style></author><author><style face="normal" font="default" size="100%">Tanina, Abdalkarim</style></author><author><style face="normal" font="default" size="100%">Wintjens, René</style></author><author><style face="normal" font="default" size="100%">Antoine, Rudy</style></author><author><style face="normal" font="default" size="100%">Brodin, Priscille</style></author><author><style face="normal" font="default" size="100%">Delorme, Vincent</style></author><author><style face="normal" font="default" size="100%">Moune, Martin</style></author><author><style face="normal" font="default" size="100%">Djaout, Kamel</style></author><author><style face="normal" font="default" size="100%">Stéphanie Slupek</style></author><author><style face="normal" font="default" size="100%">Kemmer, Christian</style></author><author><style face="normal" font="default" size="100%">Gitzinger, Marc</style></author><author><style face="normal" font="default" size="100%">Lluis Ballell</style></author><author><style face="normal" font="default" size="100%">Alfonso Mendoza-Losana</style></author><author><style face="normal" font="default" size="100%">Sergio Lociuro</style></author><author><style face="normal" font="default" size="100%">Déprez, Benoit</style></author><author><style face="normal" font="default" size="100%">David Barros-Aguirre</style></author><author><style face="normal" font="default" size="100%">Modesto J Remuiñán</style></author><author><style face="normal" font="default" size="100%">Willand, Nicolas</style></author><author><style face="normal" font="default" size="100%">Baulard, Alain R</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The small-molecule SMARt751 reverses  resistance to ethionamide in acute and chronic mouse models of tuberculosis.</style></title><secondary-title><style face="normal" font="default" size="100%">Sci Transl Med</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antitubercular Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Ethionamide</style></keyword><keyword><style  face="normal" font="default" size="100%">mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycobacterium tuberculosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Prodrugs</style></keyword><keyword><style  face="normal" font="default" size="100%">Tuberculosis</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2022</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2022 05 04</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">14</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The sensitivity of , the pathogen that causes tuberculosis (TB), to antibiotic prodrugs is dependent on the efficacy of the activation process that transforms the prodrugs into their active antibacterial moieties. Various oxidases of have the potential to activate the prodrug ethionamide. Here, we used medicinal chemistry coupled with a phenotypic assay to select the N-acylated 4-phenylpiperidine compound series. The lead compound, SMARt751, interacted with the transcriptional regulator VirS of , which regulates the operon encoding a monooxygenase that activates ethionamide. SMARt751 boosted the efficacy of ethionamide in vitro and in mouse models of acute and chronic TB. SMARt751 also restored full efficacy of ethionamide in mice infected with strains carrying mutations in the gene, which cause ethionamide resistance in the clinic. SMARt751 was shown to be safe in tests conducted in vitro and in vivo. A model extrapolating animal pharmacokinetic and pharmacodynamic parameters to humans predicted that as little as 25 mg of SMARt751 daily would allow a fourfold reduction in the dose of ethionamide administered while retaining the same efficacy and reducing side effects.&lt;/p&gt;
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