Zhao Lian, Yao Yuchao, Li Shuai, Lv Mengjiao, Chen Hua, Li Xiaoliu
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
Bioorg Med Chem Lett. 2014 Feb 1;24(3):900-4. doi: 10.1016/j.bmcl.2013.12.084. Epub 2013 Dec 27.
Novel triphenylethylene-coumarin hybrids containing two amino side chains were designed and synthesized. Some of these 3,4-diphenyl coumarins, 7b-c (the double chains at 4-position on 3-,4-phenyl, respectively), and 13b-f (the double chains at 4-position on 3-phenyl and 7-position, respectively), showed a broad-spectrum and good anti-proliferative activity against five tumor cells and low cytotoxicity in osteoblast. UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation exhibited that compounds 7b (R=piperidinyl), 7e (R=NEt2), and 7f (R=4-methylpiperazinyl) had significant interactions with Ct-DNA by the intercalative mode of binding. Structure activity relationships (SARs) analysis suggested that the location of the two amino alkyl chains would play an important role both in the compounds against tumor cells proliferation and their interactions with DNA.
设计并合成了含两条氨基侧链的新型三苯乙烯-香豆素杂化物。其中一些3,4-二苯基香豆素，7b-c（分别在3-、4-苯基的4-位上有双链）和13b-f（分别在3-苯基的4-位和7-位上有双链），对五种肿瘤细胞显示出广谱且良好的抗增殖活性，对成骨细胞的细胞毒性较低。紫外可见光谱、荧光光谱、圆二色光谱（CD）和热变性实验表明，化合物7b（R = 哌啶基）、7e（R = NEt2）和7f（R = 4-甲基哌嗪基）通过插入结合模式与Ct-DNA有显著相互作用。构效关系（SARs）分析表明，两条氨基烷基链的位置在化合物抑制肿瘤细胞增殖及其与DNA的相互作用中均起重要作用。
