3,4-二氢-4-芳基香豆素类化合物的合成及其生物活性研究

摘要

目的 设计合成一系列3,4-二氢4-芳基香豆素类化合物,并评价其抗氧化、抗肿瘤活性.方法 以取代苯甲醛为原料,经缩合及Ponndorf反应制得目标化合物.采用DPPH法测定目标化合物的抗氧化活性;采用MTT法以胃癌细胞BGC-823为测试细胞株对目标化合物进行体外抗肿瘤活性评价.结果 与结论合成了10个新的3,4-二氢4-芳基香豆素类化合物,目标化合物的结构经质谱、红外、核磁共振氢谱确证.部分化合物(3c、3d、3f、3g)具有很强的抗氧化活性,化合物3a、3c、3g、3i、3j对人胃癌细胞BGC-823具有较弱的抑制作用.%4-Aryl-3,4-dihydrocoumarins(neoflavones) represent a minor class of natural compounds which based on the C6-C3-C6 skeleton with an characteristic aryl group in the 4 position.Structurally ,4-aryl-3,4-dihydrocoumarins can also be regarded as the hybrids of isoflavones and coumarins, thus being expected to possess corresponding bioactivity.In this paper, ten 4-aryl-3,4-dihydrocoumarins were synthesized by two steps.The first condensation of substituted benzaldehydes and malonic acids in the presence of pyridine and piperidine at 70 - 90 ℃ gave the expected cinnamic acids in good yields.Then condensation of substituted cinnamic acids with appropriate phenols in the presence of BF3-Et2O and POCl3 gave the target molecule at room temperature.Their structures were confirmed by EI-MS, IR and 1H-NMR.The antioxidant and antitumor activity of these compounds were evaluated by DPPH and MTT assay, respectively.Some of 4-aryl-3,4-dihydrocoumarin derivatives showed strong scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical: ( ± ) -7,8-dihydroxy-4- ( 3-hydroxy-4-methoxyphenyl ) -3,4-dihydrocoumarin ( 3c ) EC50 = ( 2.69 ± 0.09 )μmol· L-1, ( ± )-7,8-dihydroxy-4-(4-methoxyphenyl)-3,4-dihydrocoumarin(3g) EC50 = (2.32 ±0.10)μmol· L-1 and weak antitumor in vitro activity against BGC-823 cell line [( ± )-7,8-dihydroxy-4-( 3-hydroxy-4-methoxyphenyl)-3,4-dihydrocoumarin(3c) IC50 = ( 136 ± 21 ) μmol· L-1].The results showed that the 4-arylcoumarins which possessing the catechol moiety may be a beneficial scaffold for therapeutic purpose.