Synthesis and preliminary biological evaluation of the derivatives of O^6-benzylguanine as inactivators of O^6-alkylguanine-DNA alkyltransferase

A series of new O6-BG derivatives （14-21,23-30） were synthesized as inactivators of O6-Alkylguanine-DNA alkyltransferase （AGT）, and their ability to inhibit AGT was preliminary evaluated by MTT with O6-BG as the control. The result suggested compound 30 displayed a higher activity than O6-BG.

O^6-苄基鸟嘌呤逆转人脑胶质瘤对BCNU耐药性的研究

目的 探讨提高BCNU为代表的CENUs对Mer +脑胶质瘤化疗疗效的途径。方法 采用MTT法及测定肿瘤生长观察O6 苄基鸟嘌呤 (O6 BG)预处理Mer+人脑胶质瘤细胞及荷Mer+脑胶质瘤裸小鼠对BCNU疗效的影响。结果 O6 BG能提高BCNU对Mer +胶质瘤细胞T98G的敏感性 2 2倍 ,对Mer 细胞SHG 4 4无增敏作用 ,10 μmol/LO6 BG预处理 2小时即能明显抑制MGMT活性 ,≥5 0 μmol/L时能完全抑制MGMT活性 ;O6 BG毒性极低 ,10 0 μmol/L时细胞生存率 >95 %。O6 BG +BCNU组较空白对照组延缓肿瘤生长 34 16天 ,而单纯BCNU组延缓生长 18天 (P <0 0 1) ,且O6 BG +BCNU组中还见到肿瘤暂时性退缩。结论 O6 BG通过抑制MGMT活性 ,能逆转Mer+人脑胶质瘤细胞对BCNU的耐药性 ,提高BCNU疗效 。