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核糖核苷酸还原酶的新型抑制剂——某些物理化学性质的比较

The new inhibitors of ribonucleotide reductase--comparison of some physico-chemical properties.

作者信息

Romanova D, Vachalkova A, Szekeres T, Elford H L, Novotny L

机构信息

Cancer Research Institute Slovak Academy of Sciences, Bratislava, Slovak Republic.

出版信息

J Pharm Biomed Anal. 1997 Apr;15(7):951-6. doi: 10.1016/s0731-7085(96)01937-1.

Abstract

Amidox (AX), didox (DX) and trimidox (TX), compounds synthetized as new ribonucleotide reductase inhibitors, have been investigated by ultraviolet (UV) spectrophotometry, polarography and high performance liquid chromatography (HPLC). The experiments have been performed at various pH values. The changes in UV absorption of the compounds studied were recorded and it was demonstrated that these changes are related to the pH and to structural features of the investigated molecules. From the compounds included in our series of experiments, only amidox and trimidox are reduced during polarographic experiments in Britton-Robinson buffer. The reduction of both compounds proceeded in two one-electron steps in acidic pH. One two-electron diffuse irreversible wave was observed at basic pH. The values of the half-wave potential became more negative in accordance with the increasing pH. HPLC assay also showed changes in the retention of compounds investigated, particularly when the pH of the mobile phase was close to the dissociation constant of the particular drug. The changes of physico-chemical properties detected by the all used methods are related to different chemical structures (the most significant changes were observed in alkaline pH).

摘要

作为新型核糖核苷酸还原酶抑制剂合成的化合物氨咪多(AX)、双咪多(DX)和三甲咪多(TX),已通过紫外(UV)分光光度法、极谱法和高效液相色谱法(HPLC)进行了研究。实验在不同的pH值下进行。记录了所研究化合物的紫外吸收变化,结果表明这些变化与pH值以及所研究分子的结构特征有关。在我们的一系列实验所包含的化合物中,在Britton-Robinson缓冲液的极谱实验中,只有氨咪多和三甲咪多被还原。两种化合物的还原在酸性pH条件下分两个单电子步骤进行。在碱性pH条件下观察到一个双电子扩散不可逆波。半波电位值随着pH值的升高而变得更负。HPLC分析也显示了所研究化合物保留时间的变化,特别是当流动相的pH值接近特定药物的解离常数时。所有使用方法检测到的物理化学性质的变化与不同的化学结构有关(在碱性pH条件下观察到最显著的变化)。

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