化学学报 ›› 2011, Vol. 69 ›› Issue (04): 425-430. 上一篇    下一篇

研究论文

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

李美容,蔡晓庆*,朱易峰,刘宽冠,胡茂林*   

  1. (温州大学化学与材料工程学院 温州 325035)
  • 收稿日期:2010-08-31 修回日期:2010-09-26 出版日期:2011-02-28 发布日期:2010-10-11
  • 通讯作者: 胡茂林 E-mail:hu403cn@yahoo.com.cn
  • 基金资助:

    国家自然科学基金项目;浙江省教育厅自然科学基金

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

LI Mei-Rong, CAI Xiao-Qing, ZHU Yi-Feng, LIU Kuan-Guan, HU Mao-Lin   

  1. (College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035)
  • Received:2010-08-31 Revised:2010-09-26 Online:2011-02-28 Published:2010-10-11
  • Contact: Mao-Lin Hu E-mail:hu403cn@yahoo.com.cn

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, 1b4b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2a3a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1b4b对HL-60和BEL-7402的抑制率都比较低.

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

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 (lg 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.

Key words: 5-fluorouracil derivatives, photosensitizer agents, photodynamic therapy, octanol-water partition coefficients, anticarcinogenic activity