Spectroscopic studies on <i>in vitro</i> binding of cefixime and tolcapone drugs with serum albumin

The interaction between cefixime (antibacterial) and tolcapone (Parkinson’s disease) drugs with bovine serum albumin (BSA) was investigated using several spectroscopic techniques viz. UV–Vis, fluorescence and circular dichroism. The thermodynamic parameters of the interactions were calculated, which indicated that the binding processes are spontaneous and H-bonding and van der Waals forces play a major role in BSA–cefixime interaction and hydrophobic interactions dominate BSA–tolcapone complexation. Cefixime quenches the intrinsic fluorescence of BSA by dynamic process while tolcapone through static process. The binding constant of the BSA–tolcapone complex (10⁷ L mol⁻¹) is found to be relatively higher than that of BSA–cefixime complex (10⁴ L mol⁻¹). The binding distance between BSA and cefixime and tolcapone is calculated to be 3.3 and 4.2 nm, respectively. Both fluorescence and circular dichrosim spectral studies confirmed conformational changes in BSA upon binding with these drugs. Molecular docking studies suggest the possible binding sites in the protein molecule.'本研究采用紫外-可见（UV–Vis）吸收光谱、荧光光谱及圆二色（circular dichroism, CD）光谱等多种光谱技术，探究了抗菌药物头孢克肟（cefixime）与帕金森病治疗药物托卡朋（tolcapone）分别与牛血清白蛋白（bovine serum albumin, BSA）之间的相互作用。研究计算了两种相互作用的热力学参数，结果显示二者的结合过程均为自发过程：氢键与范德华力在BSA与头孢克肟的结合过程中占据主导地位，而疏水相互作用则是BSA与托卡朋复合的主要驱动力。头孢克肟通过动态猝灭机制减弱BSA的固有荧光，托卡朋则通过静态猝灭机制实现该效果。经测定，BSA与托卡朋复合物的结合常数（10⁷ L·mol⁻¹）相对高于BSA与头孢克肟复合物的结合常数（10⁴ L·mol⁻¹）。BSA与头孢克肟、托卡朋之间的结合距离分别为3.3 nm与4.2 nm。荧光光谱与圆二色光谱研究均证实，BSA与这两种药物结合后会发生构象变化。分子对接研究则揭示了该蛋白质分子中潜在的结合位点。