Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India.
Med Chem. 2013 Mar;9(2):193-202. doi: 10.2174/1573406411309020004.
The potential of quercetin (QUE), being a member of the whole family of structurally different flavonoids, to serve as an anti-tumor agent has been recognized, but not fully understood. The interactions between DNA and a series of the flavonoids have so far been mainly investigated using a variety of experimental techniques. Herein, the specificity of QUE for DNA is explored using sophisticated density functional theory (DFT) methods employed to generate the optimized structure of QUE in complex with adenine (A), guanine (G), thymine (T) and cytosine (C), respectively. As far as a preference of QUE is concerned, structural and energetic as well as NMR chemical shift arguments clearly indicate a highest for G and a lowest for C. This observation is further substantiated by analyzing the binding modes of QUE docked in a quadruplex receptor structure of DNA and in a duplex receptor structure of DNA. Among all possible single point mutations of the DNA quadruplex and duplex residues, several critical ones causing a conspicuous stabilizing effect on the original complexes of QUE with the DNA receptors are identified. Consequently, several fundamental standpoints shedding new light on the molecular mechanisms underlying the interactions between QUE and DNA are discussed.
槲皮素（QUE）作为结构不同的黄酮类化合物家族的一员，具有作为抗肿瘤剂的潜力，这已得到认可，但尚未完全理解。迄今为止，黄酮类化合物与 DNA 之间的相互作用主要是通过各种实验技术进行研究的。在这里，使用复杂的密度泛函理论（DFT）方法来探索 QUE 与腺嘌呤（A）、鸟嘌呤（G）、胸腺嘧啶（T）和胞嘧啶（C）分别形成复合物时对 DNA 的特异性。就 QUE 的偏好而言，结构、能量和 NMR 化学位移参数清楚地表明，QUE 与 G 的结合最强，与 C 的结合最弱。通过分析 QUE 在 DNA 四链体受体结构和 DNA 双链体受体结构中的对接结合模式，进一步证实了这一观察结果。在 DNA 四链体和双链体的所有可能的单点突变中，确定了几个关键的突变，它们对 QUE 与 DNA 受体的原始复合物有明显的稳定作用。因此，讨论了几个基本观点，这些观点为 QUE 与 DNA 之间相互作用的分子机制提供了新的认识。
