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目的寻找具有抗血管生成作用的二苯并呋喃类化合物并探讨其初步构效关系。方法以苯酚类化合物、1,3-环己二烯为原料在对甲苯磺酸的催化下反应得到烷基化产物(2-环己烯基)-苯酚类化合物2a~2 e和环合产物六氢二苯并呋喃类化合物3a~3 e;2a~2 e在二(氰基苯)二氯化钯作用下环合得到1,2,3,4-四氢二苯并呋喃类化合物4a~4 e。以HUVEC、A549、Bel-7402和MCF-7为测试靶细胞,采用MTT法对目标化合物进行体外抑制内皮细胞和肿瘤细胞增殖的活性筛选。结果共合成了10个目标化合物,其结构经1H-NMR、13C-NMR、M S谱确证,3b~3 e和4b~4 e为新化合物。其中,化合物4 c、4 e对HUVEC具有良好的抑制作用并且对HUVEC具有显著的选择性。结论苯环上的羟基、烷基取代以及它们的取代位置对抑制HUVEC细胞增殖有重要影响;[4a,9a]的碳碳双键可能对化合物抑制HUVEC增殖有一定的提高作用。
OBJECTIVE To find dibenzofurans with anti-angiogenic activity and to explore their preliminary structure-activity relationship. Methods The reaction of p-toluenesulfonic acid with phenol and 1,3-cyclohexadiene as raw materials gave alkylated products (2-cyclohexenyl) -phenols 2a ~ 2e and cyclization products Hexahydrodibenzofurans 3a ~ 3 e; 2a ~ 2 e are cyclized by the action of bis (cyanophenyl) palladium dichloride to give 1,2,3,4-tetrahydrodibenzofuran 4a ~ 4 e. Using HUVEC, A549, Bel-7402 and MCF-7 as test target cells, the target compounds were screened for the activity of inhibiting the proliferation of endothelial cells and tumor cells by MTT method. Results A total of 10 target compounds were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR and M-S spectra. 3b ~ 3e and 4b ~ 4e were new compounds. Among them, compounds 4c, 4e have a good inhibitory effect on HUVEC and have a significant selectivity for HUVEC. Conclusion The substitution of hydroxyl and alkyl groups on benzene ring and their substitution positions have important effects on inhibiting the proliferation of HUVECs. The carbon-carbon double bond of [4a, 9a] may increase the inhibitory effect on the proliferation of HUVECs.