Arabpour Shiraz Zahra, Sohrabi Nasrin, Eslami Moghadam Mahboube, Oftadeh Mohsen
Chemistry Department, Payame Noor University, 19395-4697, Tehran, Iran.
Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran.
Heliyon. 2023 Sep 13;9(9):e20090. doi: 10.1016/j.heliyon.2023.e20090. eCollection 2023 Sep.
Until now, many methods have been proposed to treat cancer, such as radiation therapy and drug therapy, but none of them have caused a complete cure for cancer. Heavy metal complexes such as cisplatin are among the compounds used as drugs in chemotherapy against cancer cells. These compounds cause cell death and have anti-cancer properties, but they have side effects. The biochemical mechanism of cisplatin is related to its interaction with DNA through covalent binding. To reduce the toxicity of metallodrugs, new complexes can be designed containing S, S- bidentate ligands such as diethyldithiocarbamate. Moreover, anti-cancer compounds probably interact with proteins, such as HSA, before passing the cancerous cell membrane and DNA as a target. So, the function of proteins and their stabilities are expected to change. In this research, the mode of binding of [Pt (bpy) (amyl.dtc)]NO complex with BSA was evaluated by various thermodynamic methods. Negative binding enthalpy and entropy changes amounts show that the connection between the Platinum compound and BSA occurs via the van Der Waals type of hydrogen bond. The negative Gibbs free energy change was obtained through isothermal titration, which showed interaction proceeds spontaneously. Moreover, the emission titration data showed that protein fluorescence quenching by platinum agent titration is static. Binding, quenching constants, and binding site number were obtained by the Stern-Volmer equation, and only one binding site was determined for this interaction. A Scatchard plot with a positive slope shows the Pt agent-BSA formation is proceeding positively cooperative. The kinetic study displayed that the absorption monitoring followed the second-order model. Finally, molecular docking simulation showed that the position of the Pt agent on protein is placed I under region II.
到目前为止，已经提出了许多治疗癌症的方法，如放射疗法和药物疗法，但没有一种方法能完全治愈癌症。顺铂等重金属配合物是用于化疗抗癌细胞的化合物之一。这些化合物会导致细胞死亡并具有抗癌特性，但它们有副作用。顺铂的生化机制与其通过共价结合与DNA的相互作用有关。为了降低金属药物的毒性，可以设计含有S，S-二齿配体如二乙基二硫代氨基甲酸盐的新配合物。此外，抗癌化合物在穿过癌细胞膜和作为靶点的DNA之前，可能与蛋白质如人血清白蛋白相互作用。因此，预计蛋白质的功能及其稳定性会发生变化。在本研究中，通过各种热力学方法评估了[Pt (bpy) (戊基.dtc)]NO配合物与牛血清白蛋白的结合模式。负的结合焓和熵变表明铂化合物与牛血清白蛋白之间的连接是通过范德华型氢键发生的。通过等温滴定制得了负的吉布斯自由能变化，表明相互作用是自发进行的。此外，发射滴定数据表明铂试剂滴定引起的蛋白质荧光猝灭是静态的。通过斯特恩-沃尔默方程获得了结合、猝灭常数和结合位点数，并且确定这种相互作用只有一个结合位点。具有正斜率的斯卡查德图表明铂试剂-牛血清白蛋白的形成是正协同进行的。动力学研究表明吸收监测遵循二级模型。最后，分子对接模拟表明铂试剂在蛋白质上的位置位于区域II下方的I处。
