RT Journal Article
T1 Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor
A1 Martínez Hoyos, María
A1 Mendoza Losana, Alfonso
AB 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.
PB Elsevier
SN 2352-3964
YR 2016
FD 2016-05-08
LK https://hdl.handle.net/10016/38831
UL https://hdl.handle.net/10016/38831
LA eng
NO he research leading to these results has received funding from GlaxoSmithKline R&D the Global Alliance for TB Drug Development, and from the European Union's 7th framework program (FP7-2007-2013) under the Orchid grant agreement no. 261378.
DS e-Archivo
RD 17 jul. 2024