有机化学 ›› 2017, Vol. 37 ›› Issue (1): 122-132.DOI: 10.6023/cjoc201607020 上一篇    下一篇

研究论文

大黄酸-氨基酸缀合物的合成及初步抗肿瘤活性研究

周昌健a, 谢建伟a, 张洁a, 代斌a   

  1. a 石河子大学化学化工学院 新疆兵团化工绿色过程重点实验室-省部共建国家重点实验室培育基地 石河子 832003
  • 收稿日期:2016-07-12 修回日期:2016-08-20 出版日期:2017-01-25 发布日期:2016-09-12
  • 通讯作者: 谢建伟, 张洁 E-mail:cesxjw@foxmail.com;zhangjie-xj@163.com

Study on the Synthesis and Anti-tumor Activities of Rhein-Amino Acid Conjugates

Zhou Changjiana, Xie Jianweia, Zhang Jiea, Dai Bina   

  1. a School of Chemistry and Chemical Engineering and Key Laboratory for Green Processing of Chemical Engineering of Xin-jiang Bingtuan, Shihezi University, Shihezi 832003
  • Received:2016-07-12 Revised:2016-08-20 Online:2017-01-25 Published:2016-09-12

以大黄酸为原料,经过酯化、醚化、水解、缩合等步骤,合成了20个大黄酸-氨基酸缀合物.所有目标化合物经1H NMR,13C NMR和HRMS进行结构确证.以顺铂和阿霉素为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Hela,MCF-7,HepG2,KB和HEK293T等5株细胞)活性.结果显示2-(4,5-双(苄氧基)-9,10-蒽醌-2-甲酰氨基)-4-甲基戊酸钠(6eb)显示出较好的抗肿瘤活性,DNA对2-(4,5-二丁氧基-9,10-蒽醌-2-甲酰氨基)-4-甲基戊酸钠(6db)和6eb作用的荧光光谱均表现出荧光猝灭现象,推测6db可能仅是静电结合或分子部分嵌入DNA.

关键词: 大黄酸, 氨基酸, 抗肿瘤, 构效关系

20 novel rhein-amino acid conjugates were designed and synthesized from the rhein via esterification,etherification,hydrolysis,condensation and salification.Their structures were confirmed by 1H NMR,13C NMR and HRMS.All the target compounds were tested for cytotoxic activity against five cancer cell lines including Hela,MCF-7,HepG2,KB and HEK293T by methyl thiazolyl tetrazolium(MTT) method in vitro.The results showed that sodium(4,5-bis(benzyloxy)-9,10-dioxo-9,10-dihydroanthracene-2-carbonyl) leucinate(6eb) demonstrated moderate cytotoxic activities(IC50<50 μmol·L-1).The fluorescence of compounds sodium(4,5-dibutoxy-9,10-dioxo-9,10-dihydroanthracene-2-carbonyl) leucinate(6db) and 6eb could be both quenched by DNA.It was speculated that compound 6db interacted with DNA by the static attraction or was partially embedded into DNA.

Key words: rhein, amino acid, antitumor activity, structure-activity relationships