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

以DNA修复蛋白AGT为靶向的PET显像剂前体O^6-苄基鸟嘌呤类似物的体外初步生物评价(英文)

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.

合成一系列O6-苄基鸟嘌呤(O6-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≥O6-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。