Surfactant Research Chair, Department of Chemistry, College of Science, King Saud University, P.O. Box-2455, Riyadh 11451, Saudi Arabia.
Surfactant Research Chair, Department of Chemistry, College of Science, King Saud University, P.O. Box-2455, Riyadh 11451, Saudi Arabia.
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Oct 5;203:434-442. doi: 10.1016/j.saa.2018.05.102. Epub 2018 May 29.
For determining the pharmacological properties of medicinal compounds, their binding with serum albumins is very crucial. Herein, we have selected safranal, a major constituent of saffron which is known to retain a number of medicinal properties including antioxidant, anti-inflammatory, tumoricidal, anti-genotoxic, and anti-aging activities; and studied its mechanism of binding with human serum albumin at physiological pH using various spectroscopic methods along with computational approach using molecular docking. A change in the difference UV-visible spectrum of HSA in presence of safranal was found which is due to the complex formation. Owing to the strong absorption of safranal at the fluorescence excitation wavelength of HSA (295 nm) and in the whole range of emission, the fluorescence spectra of HSA in presence of safranal were corrected for the inner filter effect. After the correction the spectra were free from the safranal absorption effect and it was found that addition of safranal causes the quenching of HSA fluorescence and a blue shift of the emission maximum which are attributed to the binding of safranal to the protein and dominance of hydrophobic forces in the interaction, respectively. It was evident from the comparison of observed and corrected fluorescence spectra that before correction there was a large red shift while after correction appearance of blue shift was occurred. The involvement of hydrophobic interaction was also found from the extrinsic fluorescence measurements using ANS dye as well as from the analyzed thermodynamic parameters. Safranal was found to partially induce the secondary structure of HSA as construed from the CD measurements. The size of the HSA was also decreased as evident from the DLS and RLS measurements. Both site marker studies and molecular docking simulations suggested that the primary binding site of the safranal in the HSA is Sudlow's site 1 located in the subdomain IIA. Hydrophobic interaction provides the major contribution to the binding forces along with a little amount of hydrogen bonding.
为了确定药物化合物的药理学性质，它们与血清白蛋白的结合非常关键。在此，我们选择了藏红花中的主要成分藏红花醛，已知其具有多种药用特性，包括抗氧化、抗炎、杀肿瘤、抗遗传毒性和抗衰老活性；并在生理 pH 下使用各种光谱方法以及分子对接计算方法研究了其与人血清白蛋白的结合机制。发现存在藏红花醛时 HSA 的差示紫外可见光谱发生变化，这是由于形成了复合物。由于藏红花醛在 HSA 的荧光激发波长（295nm）和整个发射范围内的强烈吸收，因此校正了藏红花醛存在时 HSA 的荧光光谱的内滤效应。校正后，光谱不受藏红花醛吸收的影响，发现添加藏红花醛会猝灭 HSA 荧光并使发射最大值蓝移，这归因于藏红花醛与蛋白质的结合以及相互作用中疏水力的主导地位。从观察到的和校正的荧光光谱的比较可以明显看出，在校正之前存在较大的红移，而在校正之后出现了蓝移。从使用 ANS 染料进行的外荧光测量以及分析的热力学参数也可以发现疏水相互作用的参与。藏红花醛的圆二色性（CD）测量表明，它部分诱导了 HSA 的二级结构。从 DLS 和 RLS 测量也可以看出 HSA 的尺寸减小。位点标记研究和分子对接模拟都表明，藏红花醛在 HSA 中的主要结合部位是位于 IIA 亚域的 Sudlow 位点 1。疏水相互作用是结合力的主要贡献者，同时还有少量氢键。
