Purpose

In this work, a new water-soluble Pt(II) complex was synthesized with aliphatic glycine ligand with a formula of cis-[Pt(NH₃)₂(isopentylgly)]NO₃, as an anti-cancer drug, and characterized. To determine the binding constant of the human serum albumin (HSA, the most abundant carrier proteins in the human circulatory system) to this complex and the binding site of the complex on HSA, the melting point of HSA and the kinetics of this interaction were investigated to introduce an anti-breast cancer drug with fewer side effects.

Methods

HSA interaction with the complex was studied via a spectroscopic method at 27 and 37 °C and physiological situation (I = 10 mM, pH = 7.4) and molecular docking.

Results

The toxicity value of this complex was obtained against the human cancer breast cell line of MCF-7. The thermodynamic parameters of enthalpy and entropy were also achieved in the empirical procedure. Due to the spontaneity of the interaction, Gibbs free energy variation was obtained negative. The binding constant of this complex to HSA was 3.9 × 10⁵ (M⁻¹). Empirical results showed that the quenching mechanism was static. Hill coefficients, Hill constant, complex aggregation number around protein, number of binding sites, and protein melting temperature with complex were obtained. The kinetics of this interaction was also investigated, which showed that this interaction follows a second-order kinetic. The molecular docking data indicated that the position of the interaction of complex on the protein was the site I in the sub-second IIA. Also, the hydrogen bonding and the hydrophobic interaction as the dominant binding forces were seen in complex–HSA formation.

Conclusion

This interaction with positive cooperativity was recognized via a superior hydrogen bond. The reasonable binding constant was also obtained, which could ultimately be a good option as an anti–breast cancer drug.

中文翻译：

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抗癌铂络合物结构中脂肪甘氨酸的存在对人血清白蛋白结合的影响

目的

在这项工作中，合成了一种新的水溶性Pt（II）配合物，它是具有顺式[[Pt（NH ₃）₂（异戊基）] NO _3的脂肪族甘氨酸配体，作为抗癌药物，并进行了表征。为了确定人血清白蛋白（人类循环系统中最丰富的载体蛋白）与该复合物的结合常数以及该复合物在HSA上的结合位点，研究了HSA的熔点和这种相互作用的动力学引入副作用更少的抗乳腺癌药物。

方法

通过光谱方法在27和37°C以及生理状况（I  = 10 mM，pH = 7.4）和分子对接下研究了HSA与复合物的相互作用。

结果

获得了该复合物对人乳腺癌MCF-7细胞系的毒性值。焓和熵的热力学参数也可以在经验过程中获得。由于相互作用的自发性，吉布斯自由能变化为负。该复合物与HSA的结合常数为3.9×10 ⁵（M ^-1）。实验结果表明，淬火机理是静态的。获得了希尔系数，希尔常数，蛋白质周围的复合物聚集数，结合位点数以及具有复合物的蛋白质解链温度。还研究了这种相互作用的动力学，这表明该相互作用遵循二级动力学。分子对接数据表明复合物在蛋白质上的相互作用的位置是亚秒IIA中的位点I。另外，在复杂的HSA形成中，氢键和疏水相互作用是主要的结合力。

结论

这种具有正合作性的相互作用是通过一个优越的氢键来识别的。还获得了合理的结合常数，作为抗乳腺癌药物，最终可能是一个不错的选择。