Synthesis, characterization and molecular docking of some novel hydrazonothiazolines as urease inhibitors

A series of new hydrazonothiazolines (3a-v) was obtained in good to excellent yields (79-96%) via cyclization of the appropriate thiosemicarbazones with phenacyl bromide. The targeted compounds were characterized by advanced spectroscopic techniques, such as FTIR, (HNMR)-H-1, (CNMR)-C-13 and ESI-MS. The structure of compounds 3n and 3v was unambiguously confirmed by single crystal X-ray analysis. All compounds displayed enhanced inhibitory activity against urease enzyme with IC50 values in range of 1.73 +/- 1.57-27.3 +/- 0.655 mu M when compared to standard thiourea (IC50 = 20.8 +/- 0.75 mu M). The structure-activity relationship studies demonstrated that the activity of this series is due the central thiazole ring that interacts with nickel atoms in the active site of urease enzyme. Moreover, molecular docking studies were carried out to investigate the binding mode of all active compounds and an inactive (3u) with the active site of the urease enzyme. The docking results are in complete agreement with the experimental finding.