利用光谱和理论方法探索新设计的钯(II)配合物的生物学评价:人血红蛋白为靶标

M. Abbasi, Omid Abazari
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引用次数: 14

摘要

背景:已有研究报道钯(Pd)(II)类药物化合物与顺铂相比具有显著的抗肿瘤活性。材料与方法:本研究通过Pd (II)配合物(双吡啶乙基二硫代氨基甲酸乙酯硝酸钯II)在不同温度(25°和37°)下对人血红蛋白(Hb)功能和结构改变的抗增殖作用进行了生物学评价。此外,为了进一步的研究,多光谱方法,如荧光和远紫外圆二色(CD)的血红蛋白靶标进行了评估。结果:荧光数据显示Pd(II)配合物能够猝灭Hb的固有荧光。对两种温度下的结合常数、结合位点数量和热力学参数进行了评估,结果表明Pd (II)配合物- hb相互作用主要可能发生静电和疏水相互作用。为了评估Hb与不同浓度配合物相互作用时二级结构的变化,应用远紫外CD光谱,观察到在高剂量配合物下,发生了显著的变化,这表明过量使用该配合物会产生一些副作用。结论:钯配合物作为抗癌药物可能引起血红蛋白的结构和功能紊乱,并提高对新设计的金属抗癌药物副作用的认识。
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Probing the Biological evaluations of a new designed Palladium (II) complex using spectroscopic and theoretical approaches: Human Hemoglobin as a Target
Background : Previous studies reported that Palladium (Pd)(II) drug compounds showed significant anti-tumor activity in comparison with cis-platin. Materials and Methods : In this study, we investigated the biological evaluations of a designed Pd (II) complexes (bi pyridine ethyl dithiocarbamate palladium II nitrate) via its anti-proliferative effects on the alterations in the function and structure of human hemoglobin (Hb) at different temperatures of 25 and 37°. Also for further investigation, multi-spectroscopic methods such as fluorescence and the far-UV circular dichroism (CD) with hemoglobin target were assessed. Results : Fluorescence data showed the pure ability of Pd(II) complex to quench the intrinsic fluorescence of Hb. The binding constant, number of binding sites, and thermodynamic parameters at two temperatures were assessed and the results demonstrated the major possibility of occurring electrostatic and hydrophobic interactions in the Pd (II) complex–Hb interaction. For evaluating the change of secondary structure of Hb upon interaction with various concentrations of complex, far-UV CD spectra was applied and it was observed that in high dose of complex, significant changes occurred which is indicative of some side effects in overdosing of this complex. Conclusion : Our results suggested that using palladium complex as an anticancer agent might cause some disorders in structure and function of Hb as well as improve understanding of the side effects of newly designed metal anticancer drugs.
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