Ni(II) and Cu(II) Complexes With a Tridentate (O,N,O) Azo Dye Antipyrine‐Based Ligand: Synthesis, Spectral Characterization, Cytotoxicity, and In Silico Approaches

ABSTRACT The manuscript describes the simple and facile synthesis of a new azo‐based ligand (E)‐4‐((5‐amino‐2‐hydroxyphenyl)diazenyl)‐1,5‐dimethyl‐2‐phenyl‐1,2‐dihydro‐3H‐pyrazol‐3‐one (AHAP), and its coordination complexes (1–2) with various transition metals including nickel and copper, respectively. The ligand and each of the synthesized complexes were characterized by using various analytical techniques including melting point, molar conductivities, magnetic susceptibilities, elemental analysis (CHN), FT‐Infrared, UV–Vis spectroscopy, mass spectra, 1 H and 13 C NMR, FE‐SEM, XRD, and thermal analysis. The results showed that ligand chelated in tridentate mode (O,N,O), leading to octahedral geometry toward the present metal ions where Ni(II) and Cu(II) complexes exhibit outer sphere hybridization. The calculated particle size values of compounds reached 68.93, 71.52, and 77.94 nm for ligand, Ni(II), and Cu(II) chelates, respectively, applying the Debye–Scherrer equation on XRD patterns. The cytotoxicity of ligand and Cu(III)‐complex (2) was evaluated by an MTT cytotoxic study against the lung cancer cell lines (A‐549) and healthy human cell lines (HdFn). Cu(II) complex exhibited cytotoxicity that was greater than that of the ligand against A‐549 cell line. It is promising to use the Cu(II) complex to create novel anticancer medications. Quantum chemical calculations for ligand and its solid metal complexes were carried out utilizing the DFT of the B3LYP module. Furthermore, molecular docking studies were conducted on the A‐549 protein, associated with FGFR1 (PDB: 5UR1), using the MOE 2015 program. The ligand and the Ni(II) complex exhibit the most potent inhibitory effects on the FGFR1 protein, a receptor tyrosine kinase integral to cellular growth and differentiation. Additionally, in silico ADMET analysis predicted favorable pharmacokinetic and toxicity profiles for the synthesized molecules, indicating promising oral drug‐like properties and nontoxic nature.