Redox ranking of inducers of a cancer-protective enzyme via the energy of their highest occupied molecular orbital.
Redox ranking of inducers of a cancer-protective enzyme via the energy of their highest occupied molecular orbital.
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DOI：
10.1016/j.freeradbiomed.2004.03.008
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发表时间：
2004-06
影响因子：
7.4
通讯作者：
V. Zoete;M. Rougée;A. Dinkova-Kostova;P. Talalay;R. Bensasson
中科院分区：
文献类型：
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作者：
V. Zoete;M. Rougée;A. Dinkova-Kostova;P. Talalay;R. Bensasson
2相酶的诱导是针对癌症的化学保护的主要策略。诱导剂属于九种不同的化学类别。在这项研究中，我们发现，30种植物苯丙烯类化合物和合成类似物释放电子的趋势与其诱导NAD（P）H：醌还原酶（NQO 1）活性的效力线性相关，NQO 1是一种原型2期癌症保护酶。释放电子的趋势由最高占据分子轨道（EHOMO）的能量决定，通过简单的量子力学方法计算。观察到的相关性建立了一个明确的结论：一个代理A的绝对EHOMO越小，即，其还原电位E（A+/A）越低，其电子供体性质越强，其诱导剂效力越大。诱导剂的这种氧化还原排序的发现证明了通过一个物理化学参数（还原电位E（A+/A））控制和预测外源性物质对癌症的酶防御的基因表达的可能性。
Induction of phase 2 enzymes is a major strategy in chemoprotection against cancer. Inducers belong to nine different chemical classes. In this study we found that a measure of the tendency of 30 plant phenylpropenoids and synthetic analogs to release electrons correlates linearly with their potency in inducing the activity of NAD(P)H:quinone reductase (NQO1), a prototypic phase 2 cancer-protective enzyme. The tendency to release electrons was determined by the energy of the highest occupied molecular orbital (EHOMO), calculated by simple quantum-mechanical methods. The correlations observed establish a clear conclusion: the smaller the absolute EHOMOof an agent, A, i.e., the lower its reduction potential, E(A+/A), the stronger is its electron donor property and the greater its inducer potency. The finding of this redox ranking of the inducers demonstrates the possibility of controlling and predicting the genetic expression of an enzymatic defense against cancer by xenobiotics via one physicochemical parameter, the reduction potential, E(A+/A).