Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, P. R. China.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, P. R. China.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):759-772. doi: 10.1080/14756366.2020.1740696.
A series of furoxan derivatives of chromone were prepared. The antiproliferative activities were tested against five cancer cell lines HepG2, MCF-7, HCT-116, B16, and K562, and two normal human cell lines L-02 and PBMCs. Among them, compound exhibited the most potent antiproliferative activity. It was also found produced more than 8 µM of NO at the peak time of 45 min by Griess assay. Generally, antiproliferative activity is positively related to NO release to some extent. Further in-depth studies on apoptosis-related mechanisms showed that caused S-phase cell cycle arrest in a concentration-dependent manner and induced apoptosis significantly through mitochondria-related pathways. Human apoptosis protein array assay also demonstrated increased the expression levels of pro-apoptotic Bax, Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly up-regulated. In balance, induced K562 cells death through both endogenous and exogenous pathways.
合成了一系列色酮衍生的呋咱化合物。测试了它们对五种癌细胞系 HepG2、MCF-7、HCT-116、B16 和 K562 以及两种正常人类细胞系 L-02 和 PBMCs 的抗增殖活性。其中，化合物 表现出最强的抗增殖活性。通过格里斯测定法还发现， 在 45 分钟的峰值时间内产生了超过 8µM 的 NO。通常，抗增殖活性在某种程度上与 NO 释放呈正相关。进一步深入研究凋亡相关机制表明， 以浓度依赖的方式引起 S 期细胞周期停滞，并通过线粒体相关途径显著诱导细胞凋亡。人凋亡蛋白阵列分析还表明， 增加了促凋亡 Bax、Bad、HtrA2 和 Trail R2/DR5 的表达水平。细胞周期阻断蛋白 claspin 的表达也同样上调。在平衡中， 通过内源性和外源性途径诱导 K562 细胞死亡。
