Platinum Polyoxoniobate: Stability, Cytotoxicity, and Cellular Uptake

IF 1.1 4区化学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Russian Journal of Bioorganic Chemistry Pub Date : 2025-04-06 DOI:10.1134/S1068162024606141

A. V. Yudkina, I. P. Vokhtantsev, D. A. Rychkov, V. V. Volchek, P. A. Abramov, M. N. Sokolov, D. O. Zharkov

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Abstract

Objective: Platinum polyoxometalates are Pt (IV) complexes containing bulky cluster ligands. We have shown previously that platinum polyoxoniobate [(Nb₆O₁₉)₂{Pt(OH)₂}₂]¹²⁻ (Pt-PON1) containing two Pt centers can covalently bind DNA. Here we have addressed the structural stability of Pt-PON1 and its conjugate with guanine at the N7 position, cytotoxicity of this compound, and its accumulation in living cells. Methods: Quantum mechanical modeling was used to estimate the stability of Pt–guanine bond. Cytotoxicity of Pt-PON1 was evaluated by incubating various concentrations of the compound with cultured human and Escherichia coli cells, and the levels of intracellular Pt-PON1, by atomic emission spectroscopy. Results and Discussion: Calculations show that the Pt-PON1 complex is unstable outside the crystal lattice, while its conjugate with guanine likely undergoes structural rearrangement quite easily. A decrease in the survival of E. coli XL1-Blue and DH5α strains and human HEK293T and MCF-7 cell lines was observed already at 20 μM Pt-PON1 but at higher concentrations the compound was poorly soluble in biologically compatible media. The measured levels of intracellular Pt and Nb suggest that Pt-PON1 is efficiently taken up by human cells in a stoichiometry corresponding to the original complex. Conclusions: Platinum polyoxometalates, provided their solubility can be improved, may be considered as promising antitumor agents.

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多氧烟酸铂：稳定性、细胞毒性和细胞摄取

目的：铂多金属氧酸酯是一种含有大体积簇状配体的铂（IV）配合物。我们之前已经证明含有两个铂中心的多氧氧酸铂[(Nb6O19)2{Pt(OH)2}2]12−(Pt- pon1)可以共价结合DNA。在这里，我们讨论了Pt-PON1的结构稳定性及其在N7位置与鸟嘌呤的偶联物，该化合物的细胞毒性及其在活细胞中的积累。方法：采用量子力学模型对pt -鸟嘌呤键的稳定性进行评价。通过与培养的人和大肠杆菌细胞孵育不同浓度的化合物来评估Pt-PON1的细胞毒性，并通过原子发射光谱评估细胞内Pt-PON1的水平。结果与讨论：计算表明，Pt-PON1配合物在晶格外是不稳定的，而其与鸟嘌呤的共轭物很可能发生结构重排。在20 μM Pt-PON1浓度下，大肠杆菌XL1-Blue和DH5α菌株以及人HEK293T和MCF-7细胞系的存活率下降，但在较高浓度下，该化合物在生物相容性培养基中难溶。细胞内Pt和Nb的测量水平表明，Pt- pon1在与原始复合物对应的化学计量中被人体细胞有效地吸收。结论：铂多金属氧酸酯在提高其溶解度的条件下，可能是一种有前景的抗肿瘤药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Russian Journal of Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

1.80

自引率

10.00%

发文量

118

审稿时长

3 months

期刊介绍： Russian Journal of Bioorganic Chemistry publishes reviews and original experimental and theoretical studies on the structure, function, structure–activity relationships, and synthesis of biopolymers, such as proteins, nucleic acids, polysaccharides, mixed biopolymers, and their complexes, and low-molecular-weight biologically active compounds (peptides, sugars, lipids, antibiotics, etc.). The journal also covers selected aspects of neuro- and immunochemistry, biotechnology, and ecology.