Synthesis, In Vitro Enzymatic Inhibition, and Molecular Modeling of Novel Piperazine‐Based Bis‐Schiff Base Derivatives as Promising Anti‐urease Agents

The current study was aimed to synthesize piperazine‐based bis‐Schiff base derivatives (1–15) and were also screened in vitro for their inhibition against urease enzyme under the positive control of thiourea drug (IC50 value of 36.40±2.35 μM). Among the tested analogs, the maximum potency was shown by analog 2 with the lowest IC50 value of 2.10±1.10 μM, whereas the minimum activity was demonstrated by the scaffold 5 having an IC50 value of 49.60±6.10 μM. The experimental results of urease activity prompted us to investigate and propose a possible mechanism of how actives analogs of piperazine derivatives will interacts with the catalytic sites of targeted urease enzymes. For this purpose, molecular docking with Auto Dock Vina gave us an insight into the binding interactions of the active compounds to different amino acid residues of the targeted urease enzyme. This research study presents synthesis piperazine‐based bis‐Schiff base derivatives as urease inhibitors. Compound‐2 substituted with nitro, hydroxyl and methoxy groups is the excellent inhibitor of novel series. Molecular docking study of the potent compounds confirms the biological potency of these compounds. ADMET analysis of current study affirms the drug likeness of potent compounds.