Multi-spectroscopic and molecular modelling studies on the interaction of esculetin with calf thymus DNA.
Multi-spectroscopic and molecular modelling studies on the interaction of esculetin with calf thymus DNA.
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DOI：
10.1039/c4mb00636d
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发表时间：
2015-01
影响因子：
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通讯作者：
Tarique Sarwar;M. Husain;S. Rehman;Hassan Mubarak Ishqi;M. Tabish
中科院分区：
文献类型：
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作者：
Tarique Sarwar;M. Husain;S. Rehman;Hassan Mubarak Ishqi;M. Tabish
了解小分子与DNA的相互作用已成为化学、分子生物学和医学领域的一个活跃研究领域。植物多酚具有多种生物学和药理特性。七叶皂素是一种香豆素类多酚化合物，具有多种药理和治疗作用。然而，它与DNA的相互作用模式仍然没有被很好地理解。在本研究中，我们试图通过各种生物物理技术来确定秦皮甲素与小牛胸腺DNA(Ct-DNA)的结合方式。紫外-可见吸收光谱和荧光光谱分析表明秦皮甲素与Ct-DNA形成了络合物。结合常数为1.87×10(4)M(-1)。不同温度下的热力学参数ΔG、ΔH和ΔS表明疏水相互作用和氢键在结合过程中起主要作用。其他几个实验，如碘诱导猝灭和竞争置换研究，用溴化乙锭、吖啶橙和Hoechst 33258表明秦皮甲素可能结合在ct-DNA的小沟上。七叶皂素与Ct-DNA的结合依赖于离子强度，证实了静电相互作用的可能性。这些观察结果进一步得到DNA熔融研究、粘度测量、CD光谱分析和电子分子对接的支持。
Understanding the interaction of small molecules with DNA has become an active research area at the interface between chemistry, molecular biology and medicine. Plant derived polyphenols possess diverse biological and pharmacological properties. Esculetin is a coumarin derivative polyphenolic compound having diverse pharmacological and therapeutic properties. However, its mode of interaction with DNA is still not well understood. In the present study, we have attempted to determine the mode of binding of esculetin with calf thymus DNA (Ct-DNA) through various biophysical techniques. Analysis of UV-visible absorbance spectra and fluorescence spectra indicates the formation of a complex between esculetin and Ct-DNA. The binding constant was found to be 1.87 × 10(4) M(-1). Thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures indicated that hydrophobic interactions and hydrogen bonding played major roles in the binding process. Several other experiments such as iodide induced quenching and competitive displacement studies with ethidium bromide, acridine orange and Hoechst 33258 suggested that esculetin possibly binds to the minor groove of the Ct-DNA. The strong dependence on ionic strength in controlling the binding of esculetin with Ct-DNA confirms the possibility of electrostatic interaction. These observations were further supported by DNA melting studies, viscosity measurements, CD spectral analysis and in silico molecular docking.