Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry 605 014, India.
Centre for Bioinformatics, Pondicherry University, Puducherry 605 014, India.
Int J Biol Macromol. 2015;78:122-9. doi: 10.1016/j.ijbiomac.2015.03.036. Epub 2015 Apr 6.
Troxerutin (TXER) is a derivative of naturally occurring bioflavonoid rutin. It possesses different biological activities in rising clinical world. The biological activity possessed by most of the drugs mainly targets on macromolecules. Hence, in the current study we have examined the interaction mechanism of TXER with calf thymus DNA (CT-DNA) by using various spectroscopic methods, isothermal titration calorimetry (ITC) and molecular docking studies. Further, DNA cleavage study was carried out to find the DNA protection activity of TXER. UV-absorption and emission spectroscopy showed low binding constant values via groove binding. Circular dichroism study indicates that TXER does not modify native B-form of DNA, and it retains the native B-conformation. Furthermore, no effective positive potential peak shift was observed in TXER-DNA complex during electrochemical analysis by which it represents an interaction of TXER with DNA through groove binding. Molecular docking study showed thymine guanine based interaction with docking score -7.09 kcal/mol. This result was compared to experimental ITC value. The DNA cleavage study illustrates that TXER does not cause any DNA damage as well as TXER showed DNA protection against hydroxyl radical induced DNA damage. From this study, we conclude that TXER interacts with DNA by fashion of groove binding.
曲克芦丁（TXER）是一种天然生物类黄酮芦丁的衍生物。它在不断发展的临床领域具有不同的生物活性。大多数药物的生物活性主要针对大分子。因此，在本研究中，我们使用各种光谱方法、等温滴定量热法（ITC）和分子对接研究，研究了 TXER 与小牛胸腺 DNA（CT-DNA）的相互作用机制。此外，还进行了 DNA 切割研究，以发现 TXER 的 DNA 保护活性。紫外吸收和荧光光谱表明，通过沟结合，TXER 的结合常数值较低。圆二色性研究表明，TXER 不会修饰 DNA 的天然 B 构象，并保持其天然 B 构象。此外，在电化学分析中，TXER-DNA 复合物中没有观察到有效的正电位峰移，这表明 TXER 通过沟结合与 DNA 相互作用。分子对接研究表明，胸腺嘧啶-鸟嘌呤碱基与对接得分-7.09 kcal/mol 相互作用。该结果与实验 ITC 值进行了比较。DNA 切割研究表明，TXER 不会引起任何 DNA 损伤，并且 TXER 显示出对羟基自由基诱导的 DNA 损伤的 DNA 保护作用。从这项研究中，我们得出结论，TXER 通过沟结合与 DNA 相互作用。
