Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide

作者：Palos Isidro; Luna Herrera Julieta; Lara Ramirez Edgar E; Loera Piedra Alejandra; Fernandez Ramirez Emanuel; Guadalupe Aguilera Arreola Ma; Paz Gonzalez Alma D; Monge Antonio; Wan Baojie; Franzblau Scott; Rivera Gildardo^*

来源：Molecules, 2018, 23(6): 1453.

DOI：10.3390/molecules23061453

• esters
• quinoxaline 1,4-di-N-oxide
• Mycobacterium tuberculosis
• DNA gyrase
• drug resistance

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 mu g/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 degrees C.

• 出版日期2018-6