The small-molecule SMARt751 reverses resistance to ethionamide in acute and chronic mouse models of tuberculosis. [1]
Peer reviewed scientific article
Anglais
SCIENSANO
Auteurs
Flipo, Marion [2]; Frita, Rosangela [3]; Marilyne Bourotte [4]; Maria S Martínez-Martínez [5]; Markus Boesche [6]; Gary W Boyle [7]; Geo Derimanov [8]; Gerard Drewes [9]; Pablo Gamallo [10]; Sonja Ghidelli-Disse [11]; Stephanie Gresham [12]; Elena Jiménez [13]; Jaime de Mercado [14]; Esther Pérez-Herrán [15]; Esther Porras-De Francisco [16]; Joaquín Rullas [17]; Patricia Casado [18]; Florence Leroux [19]; Catherine Piveteau [20]; Kiass, Mehdi [21]; Vanessa Mathys [22]; Karine Soetaert [23]; Véronique Megalizzi [24]; Tanina, Abdalkarim [25]; Wintjens, René [26]; Antoine, Rudy [27]; Brodin, Priscille [28]; Delorme, Vincent [29]; Moune, Martin [30]; Djaout, Kamel [31]; Stéphanie Slupek [32]; Kemmer, Christian [33]; Gitzinger, Marc [34]; Lluis Ballell [35]; Alfonso Mendoza-Losana [36]; Sergio Lociuro [37]; Déprez, Benoit [38]; David Barros-Aguirre [39]; Modesto J Remuiñán [40]; Willand, Nicolas [41]; Baulard, Alain R [42]Mots-clés
Article written during project(s) :
Résumé:
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 booste…