The binding of drugs to plasma proteins determines its fate within the physiological system, hence profound understanding of its interaction within the bloodstream is important to understand its pharmacodynamics and pharmacokinetics and thereby its therapeutic potential. In this regard, our work delineates the mechanism of interaction of Selumetinib (SEL), a potent anti‐cancer drug showing excellent effect against multiple solid tumors, with plasma protein bovine serum albumin (BSA), using methods such as absorption, steady‐state fluorescence, time‐resolved, fluorescence resonance energy transfer, Fourier transform infrared spectra (FTIR), circular dichroism (CD), synchronous and 3D‐fluorescence, salt fluorescence, molecular docking and molecular dynamic simulations. The BSA fluorescence intensity was quenched with increasing concentration of SEL which indicates interactions of SEL with BSA. Stern–Volmer quenching analysis and lifetime studies indicate the involvement of dynamic quenching. However, some contributions from the static quenching mechanism could not be ruled out unambiguously. The association constant was found to be 5.34 × 105 M−1 and it has a single binding site. The Förster distance (r) indicated probable energy transmission between the BSA and SEL. The positive entropy changes and enthalpy change indicate that the main interacting forces are hydrophobic forces, also evidenced by the results of molecular modeling studies. Conformation change in protein framework was revealed from FTIR, synchronous and 3D fluorescence and CD studies. Competitive binding experiments as well as docking studies suggest that SEL attaches itself to site I (subdomain IIA) of BSA where warfarin binds. Molecular dynamic simulations indicate the stability of the SEL–BSA complex. The association energy between BSA and SEL is affected in the presence of different metals differently.

中文翻译：

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探索强效抗癌药物 Selumetinib 与牛血清白蛋白的相互作用：光谱和计算属性

药物与血浆蛋白的结合决定了其在生理系统中的命运，因此深入了解其在血流中的相互作用对于了解其药效学和药代动力学及其治疗潜力非常重要。在这方面，我们的工作通过吸收、稳态等方法描述了塞美替尼（SEL）这种对多种实体瘤具有优异疗效的强效抗癌药物与血浆蛋白牛血清白蛋白（BSA）的相互作用机制。荧光、时间分辨、荧光共振能量转移、傅里叶变换红外光谱 (FTIR)、圆二色性 (CD)、同步和 3D 荧光、盐荧光、分子对接和分子动力学模拟。 BSA 荧光强度随着 SEL 浓度的增加而猝灭，这表明 SEL 与 BSA 的相互作用。 Stern-Volmer 淬火分析和寿命研究表明动态淬火的参与。然而，不能明确排除静态猝灭机制的一些贡献。发现关联常数为 5.34 × 105中号−1并且它有一个单一的结合位点。福斯特距离 (r) 表示 BSA 和 SEL 之间可能的能量传输。正熵变和焓变表明主要的相互作用力是疏水力，分子模型研究的结果也证明了这一点。 FTIR、同步和 3D 荧光以及 CD 研究揭示了蛋白质框架的构象变化。竞争性结合实验以及对接研究表明，SEL 将自身附着在华法林结合的 BSA 位点 I（子域 IIA）上。分子动力学模拟表明 SEL-BSA 复合物的稳定性。 BSA 和 SEL 之间的缔合能在不同金属的存在下受到不同的影响。