Cytotoxic and ROS generation activity of anthraquinones chelate complexes with metal ions

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biometals Pub Date : 2024-09-21 DOI:10.1007/s10534-024-00632-y

Viktor A. Timoshnikov, Irina A. Slepneva, Olga A. Chinak, Olga Yu Selyutina, Nikolay E. Polyakov

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Abstract

Anthraquinones (AQs) are very effective chemotherapeutic agent, however their fundamental shortcoming is high cardiotoxicity caused by reactive oxygen species (ROS). Therefore, development of improved antitumor drugs with enhanced efficacy but reduced side effects remains a high priority. In the present study we evaluated the cytotoxicity and ROS generation activity of chelate complex of redox-active anthraquinone 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione (Q1) with iron and copper ions. Cytotoxicity study was performed using the lung cancer cell line A549 and breast cancer cell line MDA-MB-231. Q1 and Cu-Q1 complex demonstrate high activity in these experiments, but Fe-Q1 complex inactive. The ROS generation activity has been studied by EPR spin trapping technique using A549, MDA-MB-231 cell lines, and T lymphoblast cell line MOLT-4. It was shown that Q1 is able to penetrate into these cells and participate in redox reactions with the formation of a semiquinone radical. Fe(III) chelate complex formation results in much slower kinetics of ROS generation compared with pure Q1, which could be connected with a lower penetration through the cell membrane.

Graphical abstract

Abstract Image

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蒽醌类化合物与金属离子的螯合物的细胞毒性和 ROS 生成活性。

蒽醌类化合物（AQs）是非常有效的化疗药物，但其根本缺点是活性氧（ROS）导致的高心脏毒性。因此，开发疗效更好、副作用更小的改良型抗肿瘤药物仍是当务之急。在本研究中，我们评估了氧化还原活性蒽醌 2-苯基-4-（丁氨基）萘并[2,3-h]喹啉-7,12-二酮（Q1）与铁和铜离子的螯合物的细胞毒性和 ROS 生成活性。利用肺癌细胞株 A549 和乳腺癌细胞株 MDA-MB-231 进行了细胞毒性研究。在这些实验中，Q1 和 Cu-Q1 复合物表现出较高的活性，而 Fe-Q1 复合物则没有活性。利用 EPR 自旋捕获技术对 A549、MDA-MB-231 细胞系和 T 淋巴细胞系 MOLT-4 的 ROS 生成活性进行了研究。结果表明，Q1 能够渗入这些细胞并参与氧化还原反应，形成半醌自由基。与纯 Q1 相比，铁（III）螯合物的形成导致 ROS 生成的动力学速度大大降低，这可能与穿透细胞膜的能力较低有关。

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来源期刊

Biometals 生物-生化与分子生物学

CiteScore

5.90

自引率

8.60%

发文量

111

审稿时长

3 months

期刊介绍： BioMetals is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. BioMetals is an international, multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field. BioMetals offers a forum for innovative research and clinical results on the structure and function of: - metal ions - metal chelates, - siderophores, - metal-containing proteins - biominerals in all biosystems. - BioMetals rapidly publishes original articles and reviews. BioMetals is a journal for metals researchers who practice in medicine, biochemistry, pharmacology, toxicology, microbiology, cell biology, chemistry, and plant physiology who are based academic, industrial and government laboratories.