含硫(硒)醚羟喜树碱衍生物的合成及体外抗肿瘤活性初步研究  

Synthesis and evaluation of hydroxycamptothecin derivatives containing S(Se) bonds

作　　者：黄宇 廖晓雨 高慧媛[2,3] 杨鹏[1,2] HUANG Yu;LIAO Xiao-yu;GAO Hui-yuan;YANG Peng(Wuya College of Innovation henyang Pharmaceutical University,henyang 110016 China;Key Laboratory of Structure-Based Drug Design and Discovery(Shenyang Pharmaceutical University),Ministry of Education Shenyang 110016 China;School of Traditional Chinese Materia Medica,Shenyang Pharmaceutical Universiry,Shenyang 110016,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016 [2]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016 [3]沈阳药科大学中药学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2022年第7期511-517,共7页Chinese Journal of Medicinal Chemistry

基　　金：辽宁省自然科学基金项目(20180550874)。

摘　　要：目的 设计合成几种含硫(硒)醚键的羟喜树碱衍生物,并进行体外抗肿瘤活性筛选。方法 以天然产物羟喜树碱为起始原料,通过引入硫醚、硒醚及二硫醚键合成得到9个两亲性羟喜树碱衍生物。采用MTT法测试目标化合物对于人正常的肝细胞(L02)、肝癌细胞(HepG2)和人肺癌细胞(A549)的体外细胞毒性。结果与结论目标化合物均未见文献报道,其结构经H-NMR、^(13)C-NMR、HR-MS谱表征得以确证。其中含有硫醚及二硫醚键的羟喜树碱衍生物对L02细胞毒性显著降低,而对肿瘤细胞更具针对性。A series of amphiphilic hydroxy-camptothecin derivatives containing sulfide, selenide and disulfide bonds were synthesized and their antitumor activities in vitro were evaluated.By a facile synthetic route, nine novel hydroxycamptothecin derivatives were obtained and their structures were confirmed by ~1H-NMR,C-NMR and HR-MS.The cytotoxicities of the target compound to human normal hepatocytes(L02),liver cancer cells(HepG2) and human lung cancer cells(A549) in vitro were tested by MTT method.The results show that the hydroxycamptothecin derivatives containing sulfide disulfide bond significantly reduce the toxicity toward L02 while remaining its toxicity toward tumor cells.

关 键 词：羟喜树碱 抗肿瘤 肿瘤微环境 氧化还原响应 合成 

分 类 号：R914[医药卫生—药物化学]