论文部分内容阅读
经典铂抗癌药物的作用机理可根据其对肿瘤细胞DNA的双齿、双功能作用导致DNA的复制受阻来解释.最近又发现一类新的具有通式cis-[Pt(NH_3)_2(N-het)Cl]Cl(N-het是类吡啶芳香氮碱配体)的化合物具有良好的抗癌活性,但对这类抗癌药物提出了两种可能的作用机理.一种是先脱去1分子氨,然后在体内产生活性体cis-[Pt(NH_3)(N-het)]~(2+),另一种是单功能键合到 DNA上而 N-het作为一个插入基团起作用.然而,最新的实验事实排除了第一种机理,而第二种键合和插入机理又未被实验所证实.因此,研究三元配合物M(UTP)(N-bet)~(2-)分子内芳环间堆积作用有可能对这种机理提供有用的信息.本文用pH电位滴定法研究了三元Zn(UTP)L~(2-)配合物(UTP~(4-)-5’-三磷酸尿苷,L-苯并咪唑(Bi)或异喹啉(Iq))的稳定性,与咪唑(Im)相关三元配合物稳定性比较并结合~1H NMR研究结果,表明在所研究的三元配合物分子中存在着明显的芳环堆积作用.1材料与方法5’-三磷酸尿苷三钠盐(Na_2HUTP·2H_2O)购自美国Serva高级化学公司,其他试剂见参考文献[3,4] .用配有Russell CE 711/LF复合电极的Orion SA 720型pH计(美国)测定溶液的pH值.实验条件见参考文献[4].在测定三元配合物[Zn~(2+)]-[UTP~(4-)]稳定常数时,由于Zn(UTP)~(2-)配合物稳定性高,故在实?
The mechanism of action of classical platinum anticancer drugs can be explained according to its bidentate and bifunctional effect on the DNA of tumor cells resulting in the inhibition of DNA replication.Recently, a new class of compounds with the generalized cis- [Pt (NH 3) 2 (N -het) Cl] Cl (N-het is a pyridine-like aromatic nitrogen base ligand) compound has good anticancer activity, but two possible mechanisms of action for such anticancer drugs are proposed. One is to first take off 1 molecule of ammonia, and then produce the active substance cis- [Pt (NH 3) (N-het)] 2+ in vivo, and the other is monofunctionally bonded to DNA while N-het acts as an insertion group However, the latest experimental facts exclude the first mechanism, and the second mechanism of bonding and insertion has not been confirmed by experiments.Therefore, the study of the ternary complex M (UTP) (N-bet) ~ (2 -) intramolecular aromatic ring accumulation may provide useful information for this mechanism.In this paper, the potentiometric titration of ternary Zn (UTP) L ~ (2-) complex (UTP ~ (4 -) - Stability of uridine 5’-triphosphate, L-benzimidazole (Bi) or isoquinoline (Iq)) compared with the stability of ternary complexes related to imidazole (Im) In the studied ternary complex molecules With obvious aromatic ring accumulation.1 Materials and Methods Uridine trisodium 5’-triphosphate (Na 2 HUTP · 2H 2 O) was purchased from Serva Advanced Chemical Company in the United States, other reagents see reference [3,4] CE711 / LF composite electrode Orion SA 720 pH meter (USA) was used to determine the pH of the solution. The experimental conditions are described in reference [4] .In the determination of ternary complexes [Zn ~ (2 +)] - [UTP ~ 4-)] stability constant, due to the stability of Zn (UTP) ~ (2-) complex is high, so in reality?