5-氟尿嘧啶光敏性偶联衍生物的合成、表征及抗癌活性研究  

Synthesis and Biological Evaluation of Novel Coupling Derivatives of Photosensitizer and 5-fluorouracil as Antineoplastic Agents

作　　者：李美容[1] 蔡晓庆[1] 朱易峰[1] 刘宽冠[1] 胡茂林[1] 

机构地区：[1]温州大学化学与材料工程学院,温州325035

出　　处：《化学学报》2011年第4期425-430,共6页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.20571057;21071111);浙江省教育厅自然科学基金(No.Y200907137)资助项目

摘　　要：设计合成了六种新型的适用于新一代肿瘤治疗法——光动力学疗法研究的5-氟尿嘧啶(5-Fu)光敏性偶联衍生物.目标化合物的结构经过1H NMR,13C NMR,IR和元素分析确证,并通过HPLC法测定了它们及5-Fu的表观油水分配系数.其中四种化合物2a,3a,1b和4b分别采用四氮唑盐法(MTT法)对白血病细胞株HL-60和磺酰罗丹明B蛋白染色法(SRB法)对肝癌细胞株BEL-7402进行了体外抗癌活性测试.结果表明,噻吩一取代产物2a的表观油水分配系数大于二取代产物3a,与生物活性测试结果表明的2a和3a对HL-60和BEL-7402的抑制率呈正相关性;而由于N—C键过于稳定不易断裂,导致两种硝基苄基衍生物1b和4b对HL-60和BEL-7402的抑制率都比较低.Six novel conjugates of 5-fluorouracil photosensitizer for the photodynamic therapy research （PDT） were designed and synthesized. Their structures were characterized by ^1H NMR, ^13C NMR, IR and elemental analysis, 5-Fu and their octanol-water partition coefficients （1g P） were calculated by HPLC. Compounds 2a, 3a, 1b and 4b were evaluated by microculture tetrazolium assay （MTT） method for HL-60 cells and sulforhodamine B （SRB） method for BEL-7402 cells. The antitumor activities in vitro show that the compound 2a has a better inhibitory rate than 3a for both HL-60 and BEL-7402, as the octanol solubility of 2a is better than 3a. The compounds of 1b and 4b both show a moderate inhibiting effect, for the linkages of N-C is too stable to release 5-Fu.

关 键 词：5-氟尿嘧啶衍生物 光敏剂 光敏疗法 油水分配系数 抗癌活性 

分 类 号：TQ460.1[化学工程—制药化工]