Dinitrosyl 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiolyl iron complex as a promising anti-inflammatory agent: influence on cyclooxygenase-2 and interaction with serum albumin

The effect of anionic dinitrosyl iron complex (DNIC) with 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiolyl (complex 1) on cyclooxygenase-2 (COX-2, enzyme induced by inflammatory stimuli and cytokines) was examined. Complex 1 was found to be an efficient inhibitor of COX-2 functions, which provides its prospects for further study as a potential anti-inflammatory drug. The interaction of complex 1 with serum albumin, which is the basic blood carrier protein, was studied. In the presence of albumin, NO generation by complex 1 becomes more prolonged than that in a buffer solution, while the formation of a high-molecular-weight protein-bound dinitrosyl complex is observed in the system. The Stern—Volmer constant was calculated: K_SV = 5.4•10⁵ L mol⁻¹. Molecular docking shows that DNIC binding to the protein occurs at the junction of three protein domains, and the lowest energy positions of anionic complex 1 are located in subdomain Ib from the side of domain III surrounded by positively charged side groups of lysine 114 and arginines 144, 185, and 458.