Novel NO 2 semicarbazone ligand and its metal complexes as VEGFR‐2 inhibitors: Synthesis, spectral characterization, density functional theory calculations, molecular docking, and antimicrobial and antitumor evaluation

A novel semicarbazone NO 2 ligand, H 2 L , was synthesized. The ligand reacted with several metal ions such as Cu(II), Ni(II), Co(II), Fe(III), Cr(III), and Mn(II) in a molar ratio 1:1 (M:L). The H 2 L ligand and its metal complexes were characterized by electronic, infrared, mass, nuclear magnetic resonance, electron spin resonance spectra, as well as elemental analysis, thermal analysis, molar conductance, and magnetic susceptibility measurements. The Coats–Redfern equations were used to calculate the kinetic parameters (E a , A, ΔH, ΔS, and ΔG) of the thermal decomposition stages. The H 2 L ligand acts as dianionic NO 2 tridentate in all complexes and coordinates through enolate oxygen, azomethine nitrogen, and deprotonated OH group. The geometrical arrangements in all metal complexes were octahedral geometries. Based on density functional theory (DFT) level implemented in the Gaussian 09 program at B3LYP/6‐311G(d,p) level, the molecular structural parameters of the ligand and its metal complexes were calculated, and the theoretical data were connected with the experimental results. The antimicrobial activity of the current compounds was examined against Gram‐positive bacteria ( Staphylococcus aureus and Bacillus subtilis ), Gram‐negative bacteria ( Salmonella typhimurium and Escherichia coli ), yeast ( Candida albicans ), and fungus ( Aspergillus fumigatus ). The antitumor activity of the ligand and its metal complexes was investigated against HepG2 cell line, which revealed promising IC 50 values comparable with that of Cis‐platin . All synthesized compounds were also subjected to molecular docking studies to investigate their binding pattern and affinity for the VEGFR‐2 active site and correlated with antitumor data.