咖啡酸苯乙酯衍生物抑制红细胞溶血和HL-60细胞增殖活性的构效关系研究  

Structure-Activity Relationship for Anti-Haemolysis and Cytotoxicity Against HL-60 Cells of Caffeic Acid Phenethyl Ester Derivatives

作　　者：钱益平[1] 王琪[1] 曹小燕[1] 周波[1] 

机构地区：[1]兰州大学功能有机分子化学国家重点实验室,甘肃兰州730000

出　　处：《生物物理学报》2010年第4期294-300,共7页Acta Biophysica Sinica

基　　金：国家自然科学基金面上项目(20972063)~~

摘　　要：蜂胶中的主要成分咖啡酸苯乙酯作为重要的抗氧化剂和癌预防试剂分子,引起了人们相当的兴趣。为了研究其构效关系,作者通过酰基化反应合成了6个咖啡酸苯乙酯衍生物,即:咖啡酸苯乙酯(caffeic acid phenethyl ester,CAPE)、芥子酸苯乙酯(sinapic acid phenethyl ester,SAPE)、阿魏酸苯乙酯(ferulic acid phenethyl ester,FAPE)、4-羟基肉桂酸苯乙酯(4-hydroxycinnamicacid phenethyl ester,4-HCAPE)、3,5-二羟基肉桂酸苯乙酯(3,5-dihydroxycinnamic acidphenethyl ester,3,5-DHCAPE)和3-羟基肉桂酸苯乙酯(3-hydroxycinnamic acid phenethyl este,3-HCAPE)。以水溶性偶氮引发剂2,2'-偶氮二(2-脒基丙烷)二盐酸盐诱导的红细胞溶血为模型,研究了它们的抗氧化活性。根据实验测得的有效抑制溶血时间,其活性顺序为:CAPE≈4-HCAPE>SAPE>FAPE>3,5-DHCAPE>3-HCAPE。其活性显著依赖于化合物的结构(羟基的数目和位置)和亲酯性。具有邻二羟基结构的CAPE和4位羟基取代的4-HCAPE具有最高的抗氧化活性。此外,它们抑制人早幼粒白血病细胞株HL-60增殖活性也通过噻唑蓝的方法评价。有趣的是,CAPE和4-HCAPE也同样具有抑制HL-60细胞增殖活性的最好能力。这些结果提供了一种基于生物抗氧化剂的癌预防药物分子设计思路。Caffeic acid phenethyl ester has been identified as an active component of propolis, and its antioxidant and cancer chemoprevention activities have attracted considerable attention. In order to reveal the structure-activity relationship of caffeic acid phenethyl ester derivatives （ArOHs）, the authors synthesized six ArOHs, caffeic acid phenethyl ester （CAPE）, ferulic acid phenethyl ester （FAPE）, 4-hydroxycinnamic acid phenethyl ester （4-HCAPE）, sinapic acid phenethyl ester （SAPE）, 3,5-dihydroxycinnamic acid phenethyl ester （3,5-DHCAPE） and 3-hydroxycinnamic acid phenethyl ester （3-HCAPE） by preparing acyl chlorides of cinnamic acid followed by alkoxy-dehalogenation. The antioxidant capacity of the ArOHs against AAPH- induced oxidative haemolysis of red blood cells was examined. It was found that the antioxidant activity depended significantly on molecular structure （position and number of hydroxyl groups） and lipophilicity in the order of CAPE≈4-HCAPESAPEFAPE3,5-DHCAPE3-HCAPE. Compounds bearing o-dihydroxyl groups and 4-hydroxyl group on the aromatic ring （CAPE and 4-HCAPE ） were the most active. Furthermore, their antiproliferative effect on human promyelocytic leukemia （HL-60） cells was assessed by MTT method. Intriguingly, compounds with higher antioxidant activity （CAPE and 4-HCAPE） exhibited higher antiproliferative activity, which reinforces the idea of designing antioxidant-based cancer chemoprevention agents.

关 键 词：咖啡酸苯乙酯 抗氧化剂 构效关系 红细胞 癌预防试剂 

分 类 号：O629[理学—有机化学]