喹喔啉双氮氧化物衍生物的合成及其体外乏氧选择性细胞毒作用  

The Synthesis of Quinoxaline di N oxides and Their Hypoxia Selective Cytotoxity in vitro

作　　者：吴艳芬[1] 仉文升[1] 陈昕 胡枭 李五玲 汤丽霞[2] 李新愿[2] 沈恂[2] 

机构地区：[1]北京医科大学药学院 [2]中国科学院生物物理研究所

出　　处：《中国药物化学杂志》1997年第3期157-161,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金

摘　　要：生物还原性药物在肿瘤治疗中的重要意义在于它选择性地杀死肿瘤组织中对射线有对抗性的乏氧细胞，提高放疗治愈率．为此，合成了一些喹喔啉双－Ｎ－氧化物衍生物，测定了极谱半波还原电位和体外乏氧细胞毒比率．结果表明，喹喔啉环上取代基的电性效应是影响乏氧选择性细胞毒作用的重要因素，当喹喔啉环上有吸电子基团取代时，乏氧选择性毒性明显增强．The existence of hypoxic cells in tumours has long been recognized as a major problem in the cure rate of cancer by radiotherapy.The potential value of bioreductive drug in cancer therapy is that they can be used to kill those hypoxic cells in solid tumours which are resistant to radiation.SR 4233,a benzotriazine di N oxide,has been showed to be effective and to have hypoxia selective cytotoxin for hypoxic cells.The modified chemical structure of SR 4233,a series of substituted quinoxaline di N oxides was prepared by the Beirut reaction,and their reduction potentials( E 1/2 ) were measured.The hypoxia selective cytotoxicity in vitro was assayed by cloning of HeLa S3 cells.The result showed that as the electron withdrawing nature of the substituent of quinoxaline di N oxide increased,the reduction potential became more positive,and the hypoxia selectivity was increased.Thus the HCR of compound(4c) was 5 5 fold greater than that of (4a),and 9 fold greater than that of (4b).It is concluded that the electrical nature of the substituent of quinoxaline di N oxides is an important factor for hypoxia selectivity.

关 键 词：喹喔啉 生物还原性药物 细胞毒作用 双氮氧化物 

分 类 号：TQ463.54[化学工程—制药化工] R979.1[医药卫生—药品]