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Transition Metal Complexes of 2-Aminopyridine Derivatives as Cyclooxygenase Inhibitors: Stability, Spectral, and Thermal Characterization, Electrochemical Behavior, DFT Calculations, Molecular Docking, and Biological Activities

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Abstract

A series of Mn(II), Fe(III), and Co(II), complexes with two ligands derived from 2-aminopyridine, 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (L1) and 2-{[3-(trifluoromethyl)phenyl]-amino}-3-pyridinecarboxylic acid (L2), was prepared and characterized using elemental analysis, molar conductance, TG measurements, IR, UV-Vis, ESR, and magnetic measurements. The coordination mode of L1 and L2 ligands was evaluated and the different geometries around the metals were determined. A complementary computational study using density functional theory (DFT) calculations was carried out to optimize the structures of the metal complexes and to confirm the proposed geometries. Using the same theoretical method, the investigation of the frontier molecular orbitals (FMOs) was used to predict the stability/reactivity of the complexes. The study of the complexation in solution allowed the determination of the stability constants of the complexes confirming their stability in solution. The distribution of the species involving Co(II) over the whole pH-range was also studied. The electrochemical behavior of the ligands and their metal complexes was determined by cyclic voltammetry which revealed irreversible redox processes for all the compounds. The study of the biological activities of the synthesized compounds indicates that the metal complexes displayed enhanced antioxidant and antibacterial properties. Molecular docking results of the Co–L1 complex with bacterial DHPS confirmed that the metal-based compound could efficiently inhibit bacterial growth while the interactions with cyclooxygenase (COX-1 and COX-2) revealed that the compound could act as efficient anti-inflammatory drugs.

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  1. Hydrometallurgy and Molecular Inorganic Chemistry Laboratory, Faculty of Chemistry, Houari Boumediene Sciences and Technology University, 16111, Algiers, Algeria

    K. Beddar, A. Bouchoucha, M. A. Bourouai & S. Djebbar

  2. Laboratoire de Physico-Chimie Théorique et de Chimie Informatique, Faculty of Chemistry, Houari Boumediene Sciences and Technology University, 16111, Algiers, Algeria

    S. Zaater

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  1. K. Beddar
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Beddar, K., Bouchoucha, A., Bourouai, M.A. et al. Transition Metal Complexes of 2-Aminopyridine Derivatives as Cyclooxygenase Inhibitors: Stability, Spectral, and Thermal Characterization, Electrochemical Behavior, DFT Calculations, Molecular Docking, and Biological Activities. Russ J Gen Chem 93, 2578–2599 (2023). https://doi.org/10.1134/S1070363223100134

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