| 芳基异羟肟酸对核苷酸还原酶抑制机制的量子化学研究 |
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| 引用本文： | 许旋,罗一帆,蔡文正. 芳基异羟肟酸对核苷酸还原酶抑制机制的量子化学研究[J]. 药学学报, 1993, 0(1) |
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| 作者姓名： | 许旋 罗一帆 蔡文正 |
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| 作者单位： | 华南师范大学化学系，中山医科大学天然药物研究室，华南师范大学化学系 广州 510631，广州 510089，广州 510631 |
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| 摘 要： | 应用cNDO/2量子化学方法计算了28个芳基异羟肟酸化合物的电子结构,讨论了异羟肟酸化合物抑制核苷酸还原酶的作用机制。在原络合机制(仅端基部分—CONHOH与酶中金属离子M进行单位点络合)基础上,提出了新的络合机制:当芳环上存在二相邻的—OH或—NH_2时,不仅端基部分能与金属离子M络合,且这二个相邻的—OH(NH_2)中的氧(氮)原子也可以与金属离子M络合,产生双位点络合,提高了化合物抑制核苷酸还原酶的活性。这一新的络合机制合理地解释了原络合机制所无法解释的实验事实。
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| 关 键 词： | 芳基异羟肟酸 核苷酸还原酶 抑制机制 CNDO/2量化方法 |
QUANTUM-CHEMICAL STUDIES ON THE MECHANISMS OF INHIBITION OF RIBONUCLEOTIDE REDUCTASE BY ARYL HYDROXAMIC ACIDS |
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| X Xu,YF Luo and WZ Cai. QUANTUM-CHEMICAL STUDIES ON THE MECHANISMS OF INHIBITION OF RIBONUCLEOTIDE REDUCTASE BY ARYL HYDROXAMIC ACIDS[J]. Acta pharmaceutica Sinica, 1993, 0(1) |
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| Authors: | X Xu YF Luo WZ Cai |
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| Affiliation: | X Xu,YF Luo~* and WZ Cai |
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| Abstract: | By using the quantum-chemical CNDO/2 method, the mechanism of inhibition of ribonucleotide reductase by aryl hydroxamic acids has been studied. It is ascertained that the mechanism of inhibition is metal chelation. Furthermore, a new metal chelation mechanism for aryl hydroxamic acids is suggested that not only could the--CONHOH moiety chelate metal ion in ribonucleotide reductase to form uniposition chelation, but also the two adjacent hydroxyl or amino groups on benzene ring could chelate metal ion to form biposition chelation. This mechanism reasonably accounts for some experimental facts which can not be explained by the traditional metal chelation mechanism. |
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| Keywords: | Aryl hydroxamic acid Ribonucleotide reductase Inhibitory mechanism CNDO/2 quantum-chemical method |
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