Preliminary in vitro biological evaluation of novel O^6-benzylguanine derivative-precursors of PET tracers for the DNA repair protein AGT

作     者：贺巍巍 刘昭飞 刘丹 贾兵 王凡 崔育新 Wei-Wei He;Zhao-Fei Liu;Dan Liu;Bing Jia;Fan Wang;Yu-Xin Cui

作者机构：北京大学天然药物及仿生药物国家重点实验室北京100083 北京大学医学同位素研究中心北京100083 北京大学医药卫生分析中心北京100083 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2008年第17卷第1期

页      面：70-74页

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 100207[医学-影像医学与核医学] 1006[医学-中西医结合] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 08[工学] 1010[医学-医学技术（可授医学、理学学位）] 100106[医学-放射医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Beijing Science and Technology Program (Grant No. Z00004105040311) 

主　　题：O6-Benzylguanine derivatives O6-Alkylguanine DNA alkyltransferase MTT Positron emission tomography 

摘      要：A series of O6-benzylguanine （O6-BG） derivatives was synthesized, and their in vitro AGT （O^6-Alkylguanine DNA alkyltransferase） inhibitory ability was evaluated by MTT method to investigate the possibility to be promising precursors of PET tracers. O^6--BG and its derivatives, HMBG, MOBG, MOMBG, BABP and PEG, were synthesized from guanine respectively. The AGT inhibitory ability of the compounds were tested by evaluating their effects on increasing sensitivity of HeLa cancer cells to 1,3-bis （2-chloroethyl）-l-nitrosourea （BCNU） with MTT method. Their order of AGT inhibitory activities follows HMBG ≥ O^6-BG ≥ MOBG ≥ MOMBG, whereas the BABP and PEG showed no AGT inhibition activity. HMBG, MOBG and MOMBG would be promising as precursor candidates of PET tracers for tumor imaging.