Synthesis, crystal structures, molecular docking, and in vitro biological activities evaluation of transition metal complexes with 4-(3,4-dichlorophenyl) piperazine-1-carboxylic acid

• 4-(3,4-dichlorophenyl)piperazine-1-carboxylic acid was synthesised and used as a lead compound, four mononuclear Cu(II) Zn(II)and Cd(II) complexes were synthesized.
• Complexes were structurally determined by single-crystal X-ray diffraction.
• Molecular docking was investigated to explore the potential urease inhibitory activities of the complexes.
• The experimental values and docking simulation exhibited that complex 1 was a competitive inhibitor of urease.
• A preliminery exploration of Pharmacological properties of complex 1.

Three novel mononuclear complexes, [MⅡ(L)2·2H2O], (M = Cu, Ni or Cd; HL = 4-(3,4-dichlorophenyl)piperazine-1-carboxylic acid)were synthesized and structurally determined by single-crystal X-ray diffraction. Molecular docking study preliminarily revealed that complex 1 had potential urease inhibitory activity. In accordance with the result of calculation, in vitro tests of the inhibitory activities of complexes 1–3 against jack bean urease showed complex 1 (IC50 = 8.17 ± 0.91 μM) had better inhibitory activities than the positive reference acetohydroxamic acid (AHA) (IC50 = 26.99 ± 1.43 μM), while complexes 2 and 3 showed no inhibitory activities., kinetics study was carried out to explore the mechanism of the inhibiting of the enzyme, and the result indicated that complex 1 was a competitive inhibitor of urease. Albumin binding experiment and in vitro toxicity evaluation of complex 1 were implemented to explore its Pharmacological properties.

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