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

• Published in: Journal of inorganic biochemistry 2025-01, Vol.262, p.112747, Article 112747
• Main Authors: Pokidova, Оlesya V., Novikova, Veronika O., Emel’yanova, Nina S., Mazina, Ludmila M., Konyukhova, Alina S., Kulikov, Alexander V., Shilov, Gennadii V., Ovanesyan, Nikolai S., Stupina, Tatyana S., Sanina, Natalia A.
• Format: Article
• Language: English
• Subjects: Adenylate cyclase; Albumin; Animals; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - metabolism; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Glutathione; Glutathione - chemistry; Glutathione - metabolism; Guanylate cyclase; Iron - chemistry; Mucin; Mucins - chemistry; Mucins - metabolism; Nitrogen Oxides - chemistry; Nitrosyl iron complexes; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - metabolism
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2024.112747

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. Synopsis: A new promising tetranitrosyl iron complex with 2-methoxythiophenolyl, acting on the therapeutic targets of cardiovascular diseases (guanylate and adenylate cyclase), has been synthesized. In a mixture of complex with albumin and mucin, di- and mononitrosyl products are formed. In the system with GSH, complete replacement of ligands does not occur. [Display omitted] •New nitrosyl iron complex with 2-methoxythiophenolyl has been synthesized and studied.•Nitrosyl iron complex with 2-methoxythiophenolyl inhibits adenylate cyclase activity.•Nitrosyl complex with 2-methoxythiophenolyl in DMSO forms mononuclear products.•BSA, GSH and mucin affect the rate of decomposition of 2-methoxythiophenol complex.•A protein-bound complex found in a mixture of BSA and 2-methoxythiophenol complex.