Structure, properties, and decomposition in biological systems of a new nitrosyl iron complex with 2-methoxythiophenolyls, promising for the treatment of cardiovascular diseases

IF 3.8 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Inorganic Biochemistry Pub Date : 2024-09-29 DOI:10.1016/j.jinorgbio.2024.112747

Оlesya V. Pokidova , Veronika O. Novikova , Nina S. Emel’yanova , Ludmila M. Mazina , Alina S. Konyukhova , Alexander V. Kulikov , Gennadii V. Shilov , Nikolai S. Ovanesyan , Tatyana S. Stupina , Natalia A. Sanina

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引用次数: 0

Abstract

A new promising binuclear tetranitrosyl iron complex with 2-methoxythiophenolyl of the composition [Fe₂(C₇H₇OS)₂(NO)₄] (complex 1), which acts on the therapeutic targets of cardiovascular diseases, guanylate and adenylate cyclase, has been synthesized. X-ray diffraction data show the presence of two isoforms of complex 1; according to quantum chemical calculations, the structure of only the trans isomer is stable in solutions.

The processes of transformation of complex 1 in DMSO, in aqueous solutions, as well as in the presence of bovine serum albumin, reduced glutathione, and mucin were studied. DMSO promotes the decomposition of the original complex 1 into mononuclear products. In biological systems, the mechanisms of decomposition of the complex 1 differ from aqueous solutions. In albumin solution, a gradual formation of a high-molecular-weight dinitrosyl complex is observed, obtained by coordinating the [Fe(NO)₂]⁺ fragment with the amino acid groups of the protein. In the presence of mucin, an EPR signal from stable mononitrosyl products is observed. The introduction of glutathione into the system of the complex 1 leads to the replacement of one initial thioligand with glutathione. In the model systems under study, a more efficient and prolonged generation of NO groups is observed compared to a buffer solution.

The obtained data on the influence of the environment on the properties of the complex 1 in combination with a study of their effect on enzymes allow us to recommend it for further study as a potential drug with vasodilator, antianginal, and hypotensive properties.

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一种新型亚硝基铁复合物与 2-甲氧基噻吩酚的结构、性质及在生物系统中的分解，有望用于治疗心血管疾病。

我们合成了一种新的双核四亚硝基铁络合物，其成分为[Fe2(C7H7OS)2(NO)4]（络合物 1），具有 2-甲氧基噻吩基，可作用于心血管疾病的治疗靶标鸟苷酸环化酶和腺苷酸环化酶。X 射线衍射数据显示复合物 1 存在两种异构体；根据量子化学计算，只有反式异构体的结构在溶液中是稳定的。研究了复合物 1 在二甲基亚砜、水溶液以及牛血清白蛋白、还原型谷胱甘肽和粘蛋白存在下的转化过程。二甲基亚砜能促进原始复合物 1 分解成单核产物。在生物体系中，复合物 1 的分解机制与水溶液不同。在白蛋白溶液中，[Fe(NO)2]+ 片段与蛋白质的氨基酸基团配位，逐渐形成高分子量的二硝基复合物。在粘蛋白存在的情况下，可观察到稳定的单亚硝基产物产生的 EPR 信号。在复合物 1 的体系中引入谷胱甘肽会导致一个初始硫配体被谷胱甘肽取代。在所研究的模型系统中，与缓冲溶液相比，NO 基团的生成更有效、更持久。通过研究环境对复合物 1 性能的影响以及它们对酶的影响，我们建议将其作为一种具有血管扩张、抗心绞痛和降血压性能的潜在药物进行进一步研究。

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

Journal of Inorganic Biochemistry 生物-生化与分子生物学

CiteScore

7.00

自引率

10.30%

发文量

336

审稿时长

41 days

期刊介绍： The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.