Rivera Gildardo, Andrade-Ochoa Sergio, Romero Manolo S Ortega, Palos Isidro, Monge Antonio, Sanchez-Torres Luvia Enid
Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa, 88710, Mexico.
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala, s/n, 11340, D.F., Mexico.
Anticancer Agents Med Chem. 2017;17(5):682-691. doi: 10.2174/1871520616666160630175927.
Quinoxalines have shown a wide variety of biological activities including as antitumor agents. The aims of this study were to evaluate the activity of quinoxaline 1,4-di-N-oxide derivatives on K562 cells, the establishment of the mechanism of induced cell death, and the construction of predictive QSAR models.
Sixteen esters of quinoxaline-7-carboxylate 1,4-di-N-oxide were evaluated for antitumor activity on K562 chronic myelogenous leukemia cells and their IC50 values were determined. The mechanism of induced cell death by the most active molecule was assessed by flow cytometry and an in silico study was conducted to optimize and calculate theoretical descriptors of all quinoxaline 1,4-di-N-oxide derivatives. QSAR and QPAR models were created using genetic algorithms.
RESULTS & CONCLUSIONS: Our results show that compounds C5, C7, C10, C12 and C15 had the lowest IC50 of the series. C15 was the most active compound (IC50= 3.02 μg/mL), inducing caspase-dependent apoptotic cell death via the intrinsic pathway. QSAR and QPAR studies are discussed.
喹喔啉已显示出多种生物活性，包括作为抗肿瘤剂。本研究的目的是评估喹喔啉1,4 - 二 - N - 氧化物衍生物对K562细胞的活性，确定诱导细胞死亡的机制，并构建预测性定量构效关系（QSAR）模型。
评估了16种喹喔啉 - 7 - 羧酸酯1,4 - 二 - N - 氧化物对K562慢性粒细胞白血病细胞的抗肿瘤活性，并测定了它们的半数抑制浓度（IC50）值。通过流式细胞术评估最具活性分子诱导细胞死亡的机制，并进行计算机模拟研究以优化和计算所有喹喔啉1,4 - 二 - N - 氧化物衍生物的理论描述符。使用遗传算法创建了QSAR和定量性质 - 活性关系（QPAR）模型。
我们的结果表明，化合物C5、C7、C10、C12和C15在该系列中具有最低的IC50。C15是最具活性的化合物（IC50 = 3.02μg/mL），通过内源性途径诱导半胱天冬酶依赖性凋亡细胞死亡。讨论了QSAR和QPAR研究。
