【摘要】 目的提高现有抗癌药物的靶向性 ,降低其不良反应。方法采用对于增殖异常的组织具有一定亲和力的卟啉类物质作为先导化合物 ,对甲氨蝶呤进行修饰 ,合成四 对羟基苯卟啉 (ZnⅡ )甲氨蝶呤衍生物 ,并使用红外、紫外、核磁和元素分析等手段对该化合物进行表征。结果发现该化合物在细胞水平上抗EAC的IC50 值为 0 99mg/L。对小鼠体内的抗EAC实验表明在与甲氨蝶呤对照组折合相同剂量的前提下 ,动物死亡率下降了 5 0 % ,但抑瘤率仍可保持在 6 0 %以上。结论可能是由于金属锌卟啉中 ,锌有空的价电子轨道 ,在特定条件下 ,可以接受细胞膜上配体的孤电子对或成键π电子 ,形成轴向配位化学建 ,使得卟啉环易于吸附并穿过细胞膜 ,在卟啉的介导下 ,锌卟啉甲氨蝶啉衍生物产生靶向性分布 ,从而减少了它的不良反应 ,并保留其抗癌活性。更多还原

【Abstract】 Aim To improve the target activity of anticancer medicines and reduce their untoward effects.Method Methotrexatum was modified by use of metal zinc porphyrin.The compound was characterized by IR,UV, 1H NMR and elementary analysis.Results The anticancer activities at the cell level were tested by EAC,IC 50 was 0 99 μg/mL,anticancer activities in vivo test in mice were tested by EAC,the cancer control rate was above 60% in the same dose in the control group.But the death rate of the mice decreased by 50% than the control group.Conclusion There is empty valence electron orbit in the zinc of metal zinc porphyrin,it is possible that they can accept the lone electron pair from the cell membrane ligand under suitable conditions for the formation of the axial coordinate bond.It makes porphyrin pass the cell membrane easily.Methotrexatum was distributed and specialized by the guide of porphyrin.Maybe it results in reduction of the untoward effect and retention of anticancer activities.更多还原