Bioactivity and computational studies on the induction of urease inhibition by three Cu(II) complexes with a fluorinated Schiff base and different secondary ligands

Urease inhibition studies of three Cu(II) complexes with a fluorinated Schiff base ligand and different secondary ligands: An experimental and computational study. [Display omitted] •Three metal complexes of O-N-O Schiff base were synthesized with three different secondary ligands and their urease inhibitory activity was studied.•DFT calculations of three Cu(II) complexes were described.•Their structure-inhibitory activity relationships were discussed.•The 100-ns molecular dynamic (MD) simulations were performed. Three mononuclear Cu(II) complexes, [Cu(C16H12NO3F)(H2O)] (C1), [Cu(C16H12NO3F)(C10H9N3)]·H2O·0.5CH3OH (C2) and [Cu(C16H12NO3F)(C3H4N2)] (C3) with a fluorinated Schiff base ligand (C16H12NO3F = 5-fluorosalicylaldehyde-L-phenylalanine) and different secondary ligands (C10H9N3 = 2,2′-dipyridylamine; C3H4N2 = imidazole) were synthesized and structurally characterized. Theoretical calculation of the three complexes was carried out by density functional theory (DFT) Becke's three-parameter hybrid (B3LYP) method using the Gaussian 09 package. The calculation results are in accordance with experimental results. In addition, the inhibitory activities of C1-C3 were tested in vitro against jack bean urease. At the same time, molecular docking was investigated to determine the probable binding mode. The experimental values and docking simulation exhibited that C1 showed strong inhibitory activity (IC50 = 0.68 ± 0.09 μM) compared with the positive reference acetohydroxamic acid (IC50 = 27.73 ± 2.93 μM). Moreover, a 100-ns molecular dynamics (MD) simulation was performed to evaluate the stability of urease (PDB ID: 3LA4) and the binding stability of the 3LA4/C1 and 3LA4/C3 using the Desmond 2021 from Schrödinger. Their structure-inhibitory activity relationship was further discussed from the perspective of molecular docking, theoretical calculation and molecular dynamics simulation.