A synthetic chalcone as a potent inducer of glutathione biosynthesis.
A synthetic chalcone as a potent inducer of glutathione biosynthesis.
复制标题
DOI：
10.1021/jm2016073
复制
发表时间：
2012-02-09
影响因子：
7.3
通讯作者：
Boumendjel, Ahcene
中科院分区：
文献类型：
--
作者：
Kachadourian, Remy;Day, Brian J.;Pugazhenti, Subbiah;Franklin, Christopher C.;Genoux-Bastide, Estelle;Mahaffey, Gregory;Gauthier, Charlotte;Di Pietro, Attilio;Boumendjel, Ahcene
查尔酮类化合物因其抗炎和抗血管生成的特性而继续引起人们的极大兴趣。我们最近报道了2‘，5’-二羟基查尔酮(2‘，5’-DHC)能够诱导乳腺癌耐药蛋白介导的谷胱甘肽(GSH)输出和c-Jun氨基末端激酶介导的细胞内GSH水平升高。在此，我们报道了一系列含有羟基、甲氧基和卤素(F和Cl)取代基的30个合成查尔酮衍生物的构效关系及其提高细胞内GSH水平的能力。最优结构2-氯-4‘，6’-二甲氧基-2‘-羟查尔酮，诱导了有效的核因子-E2相关因子2介导的转录反应和谷氨酸半胱氨酸连接酶全酶的形成，如在抗氧化反应元件驱动下稳定表达荧光素酶报告基因的人乳腺癌细胞株所示。
Chalcones continue to attract considerable interest due to their anti-inflammatory and antiangiogenic properties. We recently reported the ability of 2′,5′-dihydroxychalcone (2′,5′-DHC) to induce both breast cancer resistance protein-mediated export of glutathione (GSH) and c-Jun N-terminal kinase-mediated increased intracellular GSH levels. Herein, we report a structure–activity relationship study of a series of 30 synthetic chalcone derivatives with hydroxyl, methoxyl, and halogen (F and Cl) substituents and their ability to increase intracellular GSH levels. This effect was drastically improved with one or two electrowithdrawing groups on phenyl ring B and up to three methoxyl and/or hydroxyl groups on phenyl ring A. The optimal structure, 2-chloro-4′,6′-dimethoxy-2′-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements.
登录
查看更多内容
DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
9.7
作者：
Bernhard, D;Schwaiger, W;Csordas, A
通讯作者：
Csordas, A
影响因子：
7.4
作者：
Kachadourian, Remy;Day, Brian J.
通讯作者：
Day, Brian J.
影响因子：
10.6
作者：
Forman, Henry Jay;Zhang, Hongqiao;Rinna, Alessandra
通讯作者：
Rinna, Alessandra
影响因子：
5.8
作者：
Kachadourian, R;Johnson, CA;Day, BJ
通讯作者：
Day, BJ