Identification and molecular modeling of new quinolin-2-one thiosemicarbazide scaffold with antimicrobial urease inhibitory activity.

A new series of 6-substituted quinolin-2-one thiosemicarbazides 6a-j has been synthesized. The structure of the target compounds was proved by different spectroscopic and elemental analyses. All the designed final compounds were evaluated for their in vitro activity against the urease-producing R. mucilaginosa and Proteus mirabilis bacteria as fungal and bacterial pathogens, respectively. Moreover, all compounds were in vitro tested as potential urease inhibitors using the cup-plate diffusion method. Compounds 6a and 6b were the most active with (IC = 0.58 ± 0.15 and 0.43 ± 0.09 µM), respectively, in comparison with lead compound I (IC = 1.13 ± 0.00 µM). Also, the designed compounds were docked into urease proteins (ID: 3LA4 and ID: 4UBP) using Open Eye software to understand correctly about ligand-receptor interactions. The docking results revealed that the designed compounds can interact with the active site of the enzyme through multiple strong hydrogen bonds. Moreover, rapid overlay of chemical structures' analysis was described to understand the 3D QSAR of synthesized compounds as urease inhibitors. The results emphasize the importance of polar thiosemicarbazide directly linked to 6-substituted quinolone moieties as promising antimicrobial urease inhibitors.