Unidad Académica Multidisciplinaria Reynosa-Rodhe, Universidad Autónoma de Tamaulipas, Carr. Reynosa-San Fernando, s/n, Reynosa 88779, Mexico.
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico.
Molecules. 2018 Jun 15;23(6):1453. doi: 10.3390/molecules23061453.
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--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--oxide derivatives in vitro against (pansusceptible and monoresistant strains). Additionally, the inhibitory effect of esters of quinoxaline 1,4-di--oxide on 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 (, , , , , , and ) 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, showed a high stability after 24 h in human plasma at 37 °C.
结核病仍然是全球公共卫生问题，耐药性是其治疗的主要障碍。喹喔啉 1,4-二氧化物已被提议作为设计新药物来对抗这种疾病的支架。为了研究该化合物的疗效，本研究评估了体外对 （泛敏感和单耐药株）的喹喔啉 1,4-二氧化物衍生物的甲酯、乙酯、异丙酯和正丙酯的抑制作用。此外，还研究了喹喔啉 1,4-二氧化物酯对拓扑异构酶超螺旋的抑制作用，并通过超高效液相色谱-串联质谱法（UPLC-MS）进行了稳定性分析。结果表明，有 8 种化合物（ 、 、 、 、 、 、 ）具有与参考药物异烟肼（最低抑菌浓度（MIC）=0.12 µg/mL）相似的活性，对非复制细胞和单耐药株均有作用。构效关系分析表明，7 位酯基的空间位阻是增强其生物学效应的关键。此外， 在 37°C 下，人血浆中 24 小时后具有较高的稳定性。
