以DNA修复蛋白AGT为靶向的PET显像剂前体O6-苄基鸟嘌呤类似物的体外初步生物评价

摘要

合成一系列06-苄基鸟嘌吟(06-BG)类似物,并且采用MTT.法评价其体外对DNA修复蛋白AGT的抑制作用,探讨其作为潜在的正电子发射断层成像技术(PET)显像剂前体的可能性.以鸟嘌呤作为起始原料分别合成了o6-BG及其类似物HMBG,MOBG,MOMOBG,BABP和PEG.采用MTT方法,通过测定合成产物增强HeLa细胞对1,3-双(2-氯乙基)亚硝基脲(BCNU)药物敏感性的强弱来评价其对AGT的抑制作用.合成产物对AGT抑制活性强弱排序为HMBG≥06-BG≥MOBG≥MOMBG,而BABP和PEG基本未表现出任何的AGT抑制活性.HMBG,MOBG和MOMBG具有良好的体外活性.其正电子核素标记物可能成为有前景的用于肿瘤AGT显像的PET显像剂.%A series of O6-benzylguanine (O6-BG) derivatives was synthesized,and their in vitro AGT (O6-Alkylguanine DNA alkyltransferase) inhibitory ability was evaluated by MTT method to investigate the possibility to be promising precursors of PET tracers.O6-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 ≥ O6-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.