2024-03-28T13:17:19Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/65962023-10-05T13:27:07Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
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
2352-3964
http://hdl.handle.net/20.500.12105/6596
27428438
10.1016/j.ebiom.2016.05.006
2352-3964
EBioMedicine
Antibiotic
Bactericidal
Catalase
Drug discovery
InhA
Single-cell imaging
Tuberculosis
Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor