New 4-thiazolidinone/quinoline-2-ones scaffold: Design, synthesis, docking studies and biological evaluation as potential urease inhibitors

• Synthesis of two series of 6-substituted 2-quinolone 4-thiazolidinone derivatives. • The structure of the target compounds was proved by different spectroscopic together with elemental analysis. • Some compounds showed outstanding urease inhibitory with approximately ~10–50 fold more potent than thiourea. • The binding interactions of these compounds were confirmed through molecular docking studies. • The correlation between the structure moieties and urease inhibition activity was discussed. Synthesis of two series of 6-substituted 2-quinolone 4-thiazolidinone derivatives 3a-i and 4a-c was achieved. The structure of the target compounds was proved by different spectroscopic including NMR, mass and IR spectra as well as elemental analysis. All the designed final compounds exhibited varied degrees of urease inhibitory activity with IC 50 values 0.46–27.1 μM compared with the standard thiourea having which exhibit IC 50 value of 21.9 ± 0.89 μM. Compounds 3b, 3d and 3e showed outstanding urease inhibitory potential with IC 50 values of 0.92±0.17, 0.74±0.14 and 0.46±0.04 μM, respectively, which is much better than the standard thiourea. The binding interactions of these compounds were confirmed through molecular docking studies; the most active compounds displayed complete overlay and a similar binding mode and pose with the reference. Both compound 3d with the standard ligand inside the urease proteins (ID: 4UBP)