Esters Quinoxaline 1,4-di-N-oxide Mycobacterium tuberculosis DNA gyrase Drug resistance
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Palos, I. (Isidro); Luna-Herrera, J. (Julieta); Lara-Ramírez, E. (Edgar E.); et al. "Anti-mycobacterium tuberculosis activity of esters of quinoxaline 1,4-Di-N-Oxide". Molecules. 23 (6), 2018, 1453
Tuberculosis continues to be a public health problem in the world, and drug resistance has
been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold
to design new drugs to combat this disease. To examine the efficacy of this compound, this study
evaluates methyl, ethyl, isopropyl, and n-propyl esters of quinoxaline 1,4-di-N-oxide derivatives
in vitro against Mycobacterium tuberculosis (pansusceptible and monoresistant strains). Additionally,
the inhibitory effect of esters of quinoxaline 1,4-di-N-oxide on M. tuberculosis gyrase supercoiling
was examined, and a stability analysis by ultra performance liquid chromatography-tandem
mass spectrometry (UPLC-MS) was also carried out. Results showed that eight compounds
(T-007, T-018, T-011, T-069, T-070, T-072, T-085 and T-088) had an activity similar to that of the
reference drug isoniazid (minimum inhibitory concentration (MIC) = 0.12 µg/mL) with an effect
on nonreplicative cells and drug monoresistant strains. Structural activity relationship analysis
showed that the steric effect of an ester group at 7-position is key to enhancing its biological effects.
Additionally, T-069 showed a high stability after 24 h in human plasma at 37 ◦C.