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  

Synthesis and pharmacological activities of 4-aryl-3,4-dihydrocoumarin derivatives

作　　者：孙捷[1,2] 丁为现[3] 高艳明[3] 高蓝[3] 武玉平[3] 邹永[1] 

机构地区：[1]中国科学院广州化学研究所,广东广州510650 [2]中国科学院研究生院,北京100039 [3]南京农业大学生命科学研究院动物系,江苏南京210095

出　　处：《中国药物化学杂志》2011年第1期19-24,共6页Chinese Journal of Medicinal Chemistry

基　　金：广东省科技计划项目(2003B31603,2006B35604002);国家科技支撑计划项目(2007BAD82B02);广东省-中国科学院战略合作计划项目(2009B091300125)

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.

关 键 词：化合物制备 3 4-二氢-4-芳基香豆素类化合物 抗肿瘤活性 抗氧化活性 

分 类 号：R284[医药卫生—中药学]