三乙烯四胺基淀粉的合成及抗癌活性  

Synthesis of triethylenetetramine-starch and its antitumor effects

作　　者：程如梅[1] 步叶旭 

机构地区：[1]温州医科大学眼视光学院,纳米生物材料研究所,浙江温州325027

出　　处：《温州医科大学学报》2016年第1期19-23,共5页Journal of Wenzhou Medical University

基　　金：国家自然科学基金资助项目(21405115);浙江省医药卫生科研项目(2015KYB254);温州市科技局科技计划项目(Y20120218);温州医科大学附属眼视光医院项目(YNCX2014 08)

摘　　要：目的:设计合成高分子基多胺抗癌药物(三乙烯四胺基淀粉,CTS),研究其对人端粒DNA d[G3(T2AG3)3]的作用机制和细胞毒性,提供高分子靶向抗癌药物的另一种开发思路。方法:以三乙烯四胺为出发点,通过环氧氯丙烷为桥梁连接到廉价淀粉上获得化合物CTS,通过各种光谱手段对CTS进行表征,运用圆二色CD光谱研究其与人端粒DNA的相互作用机制,采用CCK-8方法研究CTS对人眼脉络膜黑色素瘤(OCM-1)细胞的抑制作用。结果:CTS可以诱导人端粒DNA形成反平行G-四链体,对于OCM-1细胞具有较强的毒性,可以抑制其生长,而CTS对正常的人视网膜色素上皮(ARPE-19)细胞毒性极低,表明CTS可以作为以G-四链体为靶点的癌细胞潜在的靶向药物。结论:CTS可以促进G-四链体的生成,并对OCM-1细胞具有较强的抑制性,而对正常细胞影响微小。Objective： To design and synthesize the potential antitumor drug, CTS （triethylenetetramine-starch）. Its interactions with the human telomere DNA （d[G3（T2AG3）3 series]） and cytotoxicity to OCM-1 tumor cells are investigated. As a consequence, it provides a new strategy to develop targeted antitumor drugs. Methods： The triethylenetetramine reacted with the epichlorohydrin crosslinked-starch （CS） to produce the CTS. It was characterized by various methods. The circular diehroism （CD） spectra were used to clarify the interaction mechanism between the CTS and human telomere DNA. Its cytotoxity to OCM-1 cells was determined by CCK- 8 method. Results： The antiparallel G-quadruplex could be induced and stabilized by CTS. This may be the reason that CTS inhibited the growth of OCM-1 cells, and moreover it showed very low cytotoxicity to ARPE-19 human cells. Such observations indicated that CTS was a promising antitumor drug. Conclusion： The CTS can stabilize the G-quadruplex and has higher cytotoxicity to OCM-1 cells. It has insignificant effects on the growth of normal human cells.

关 键 词：三乙烯四胺基淀粉 G-四链体 CD光谱 抗癌 

分 类 号：R979.1[医药卫生—药品]