基于肿瘤靶向的水飞蓟宾-氨基酸席夫碱的合成及性质研究  

Study on synthesis silibinin-amino acids schiff base and properties based on tumor targeting

作　　者：赵佳楠[1] 张宇[1] 李响[1] 沙靖全[1] 张羽男[1] 王朝兴[1] 

机构地区：[1]黑龙江省高校生物药制剂重点实验室佳木斯大学药学院,黑龙江佳木斯154007

出　　处：《分子科学学报》2015年第2期134-139,共6页Journal of Molecular Science

基　　金：黑龙江省教育厅资助项目(12511575);佳木斯大学研究生科技创新基金资助项目(LZZ2014_032);佳木斯大学晶体药物科技创新团队项目(CXTD-2013-05)

摘　　要：以水飞蓟宾和氨基酸为原料,通过常规方法合成了一系列具有靶向性的水飞蓟宾-氨基酸席夫碱,并对其抗肿瘤作用进行研究.采用核磁共振碳谱、质谱和红外光谱对已合成的水飞蓟宾-氨基酸席夫碱(氨基酸=甘氨酸(1)、丙氨酸(2)、赖氨酸(3)、苯丙氨酸(4)、谷氨酸(5)、半胱氨酸(6))进行结构表征.采用MTT法对化合物1-6及水飞蓟宾进行抗肝癌细胞SMMC-7721的活性研究,抑制率分别为70.2%,53.7%,47.8%,55.6%,49.2%,51.8%,33.3%.体外抗肿瘤活性实验表明,水飞蓟宾-氨基酸席夫碱系列化合物对人肝癌细胞株SMMC-7721均有抑制作用,且明显高于水飞蓟宾母核.实现了以氨基酸为载体,将具有抗肿瘤活性的天然药物靶向运输至癌细胞内,极具肝靶向药物开发潜力.A series of tumor targeted silibinin-amino acids schiff base compounds based on silibinin and amino acid have been synthesized under conventional conditions.The anti-tumor activities of compounds are also carried out.All these compounds,namely,（1）silibinin glycine schiff base,（2）silibinin alanine schiff base,（3）silibinin lysine schiff base,（4）silibinin phenylalanine schiff base,（5）silibinin glutamic acid schiff base and（6）silibinin cysteine schiff base have been structurally characterized by nuclear magnetic resonance spectroscopy,mass spectrometry and infrared spectra.The antitumor activities in vitro of compounds and silibinin on SMMC-7721 cells are studied by MTT experiments,and the inhibit ratio are 70.2%,53.7%,47.8%,55.6%,49.2%,51.8%and 33.3%,respectively.Interestingly,the results of the antitumor activity in vitro showed that compounds displayed high ability of inhibiting effect on SMMC-7721 cells than nuclear parent.The successful isolation of six novel compounds not only provides intriguing example of amino acids as carrier,but also presents a very useful ability to act as targeted natural drugs towards tumor cells,opening the door to the synthesis of many more charming targeted drugs with a simple synthetic strategy.

关 键 词：水飞蓟宾 氨基酸 席夫碱 抗肿瘤 靶向 

分 类 号：O643[理学—物理化学]