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oai:repisalud.isciii.es:20.500.12105/65962024-09-27T23:02:28Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Martínez-Hoyos, María author Perez-Herran, Esther author Gulten, Gulcin author Encinas, Lourdes author Álvarez-Gómez, Daniel author Alvarez, Emilio author Ferrer-Bazaga, Santiago author García-Pérez, Adolfo author Ortega, Fátima author Angulo-Barturen, Iñigo author Rullas, Joaquin author Blanco Ruano, Delia author Torres, Pedro author Castañeda, Pablo author Huss, Sophie author Fernández Menéndez, Raquel author González Del Valle, Silvia author Ballell, Lluis author Barros, David author Modha, Sundip author Dhar, Neeraj author Signorino-Gelo, François author McKinney, John D author García-Bustos, Jose Francisco author Lavandera, Jose Luis author Sacchettini, James C author Jimenez, M Soledad author Martín-Casabona, Nuria author Castro-Pichel, Julia author Mendoza-Losana, Alfonso author 2016-06-08 Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment. EBioMedicine. 2016; 8:291-301 10.1016/j.ebiom.2016.05.006 2352-3964 2352-3964 EBioMedicine 27428438 http://hdl.handle.net/20.500.12105/6596 Antibiotic Bactericidal Catalase Drug discovery InhA Single-cell imaging Tuberculosis Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor