School of Chemistry and Environment, South China Normal University, Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education, Guangzhou 510006, China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Eur J Med Chem. 2017 Oct 20;139:84-94. doi: 10.1016/j.ejmech.2017.08.005. Epub 2017 Aug 4.
An efficient route without metal catalyst has been developed for synthesis of 4-biphenylamino-5-halo-2(5H)-furanones. The antitumor activities against various tumor cells of all the compounds have been evaluated by MTT assay. Among them, the compound 3j exhibits significant inhibitory activity against MCF-7 human breast cancer cells with an IC value of 11.8 μM and low toxicity toward HaCaT human normal cells. The mechanism studies confirm that 3j can induce cell cycle arrest at G2/M phase in MCF-7 cells. Compared with compound 3e, 3j has stronger binding affinity to c-myc G-quadruplex (G4) DNA via π-π stacking and H-bonding interactions. Western blot analysis also further confirms that compound 3j can down-regulate the expression of c-myc in MCF-7 cells.
已经开发出一种无需金属催化剂的有效途径来合成 4-联苯氨基-5-卤代-2(5H)-呋喃酮。通过 MTT 测定法评估了所有化合物对各种肿瘤细胞的抗肿瘤活性。其中，化合物 3j 对 MCF-7 人乳腺癌细胞具有显著的抑制活性，IC 值为 11.8 μM，对 HaCaT 人正常细胞的毒性较低。机制研究证实，3j 可诱导 MCF-7 细胞的细胞周期停滞在 G2/M 期。与化合物 3e 相比，3j 通过 π-π 堆积和氢键相互作用与 c-myc G-四链体 (G4) DNA 具有更强的结合亲和力。Western blot 分析也进一步证实，化合物 3j 可以下调 MCF-7 细胞中 c-myc 的表达。
