摘要
色胺酮（Tryptanthrin，Try）是重要的天然吲哚喹唑啉类生物碱，本文首次合成了2，8-二溴色胺酮（Br-Try）及8-碘色胺酮（I-Try），并研究其抗肿瘤活性；以G-四链体DNA为靶点研究其作用机制。化合物与BEL-7404、HepG2、NCI．H460、Tj24等四种肿瘤细胞株的体外抗肿瘤活性和HL-7702正常肝细胞株的毒性实验表明，Br-Try和I-Try表现出比Try的抗肿瘤活性有不同程度的增强，而对正常细胞毒性减弱的结果。Br—Try对BEL-7404、NCI-H460和T-24肿瘤细胞株表现出比Try和顺铂更强的抗肿瘤活性，IC50值在7．08～9．68p．M，而I-Try只对HepG2细胞株表现了比Try和顺铂增强的抑制活性，Ic50值为15．78±0．33μM。初步的作用机制分析表明，三种化合物与G一四链体DNA有较强作用．以Br-Try最强。
Tryptanthrin is a type of important natural quinazolineindole alkaloids. In this study, the synthesis, antl-tumor activities and G-quadruplex DNA binding effect of 2,8-dibromo-tryptanthrins （Br-Try）, 8-indo-tryptanthrin （I-Try） were investigated. The in vitro anti-tumor activities against 4 tumor cell lines BEL-7404, HepG2, NCI-H460, T-24 and HL-7702 showed that both Br-Try and I-Try exhibited stronger anti-tumor activity than tryptanthrin and cis-platium a- gainst certain cell hnes. Br-Try exhibited better activities than cis-platium and Try against BEL-74（M, NCI-H460 and T- 24 with IC50 values of 7.08-9.68 μM. While, I-Try only inhibited against HepG2 with ICso value of 15.78 ± 0.33 μM. Spectroscopic experiments showed that the three compounds had stabilizing effect on G-quadruplex HTG21 DNA, in which Br-Try showed the strongest effect.
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2016年第8期1300-1304,共5页
Natural Product Research and Development
基金
国家自然科学基金(21261025)
药用资源化学与药物分子工程教育部重点实验室资助项目(CMEMR2011-09
CMEMR2014-B08)
广西高校科学技术重点项目(ZD2014108)
广西高校农产品加工与安全技术高水平创新团队及卓越学者计划
广西科学技术研究项目(1346008-4)
广西自然科学基金(2014GXNSFAA11871)
关键词
色胺酮
卤代衍生物
抗肿瘤活性
G4-DNA
tryptanthrin
halogenated derivatives
anti-tumor activity
G-quadruplex DNA
