• Baptiste Villemagne, Arnaud Machelart, Ngoc Chau Tran, Marion Flipo, Martin Moune, Florence Leroux, Catherine Piveteau, Alexandre Wohlkönig, René Wintjens, Xue Li, Ruxandra Gref, Priscille Brodin, Benoit Deprez, Alain R Baulard, and Nicolas Willand.
• Univ. Lille, Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for Living Systems, F-59000 Lille, France.
• ACS Infect Dis. 2020 Mar 13; 6 (3): 366-378.

AbstractKilling more than one million people each year, tuberculosis remains the leading cause of death from a single infectious agent. The growing threat of multidrug-resistant strains of Mycobacterium tuberculosis stresses the need for alternative therapies. EthR, a mycobacterial transcriptional regulator, is involved in the control of the bioactivation of the second-line drug ethionamide. We have previously reported the discovery of in vitro nanomolar boosters of ethionamide through fragment-based approaches. In this study, we have further explored the structure-activity and structure-property relationships in this chemical family. By combining structure-based drug design and in vitro evaluation of the compounds, we identified a new oxadiazole compound as the first fragment-based ethionamide booster which proved to be active in vivo, in an acute model of tuberculosis infection.

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