<i>In-Silico</i> DFT, ADMET Prediction, Toxicological Assessment and Molecular Modeling Studies of Hydrazone-Derived Thiazolidinone Derivatives: Insight into <i>In-vitro</i> Urease Activity, and Kinetic Mechanism Investigations

A series of hydrazones 4(a-u) and 4-thiazolidinones 5(a-m) were synthesized, structurally characterized through 1 H NMR and EI–MS, and subjected to biological evaluation for urease inhibitory activity. The hydrazones and 4-thiazolidinones demonstrated urease inhibitory activity to varying extents, with IC 50 values for hydrazones ranging from 48.7 ± 5.59–353.6 ± 5.77 [Formula: see text]M, and for 4-thiazolidinones from 27.7 ± 5.58–176.3 ± 5.57 [Formula: see text]M, respectively, relative to the reference compound, thiourea, which displayed an IC 50 of 21.8 ± 1.51 [Formula: see text]M. Thiazolidinones were found to be more active than hydrazones and among the series of 4-thiazolidinones, derivatives 5h, 5g and 5k demonstrated significant inhibition, exhibiting IC 50 values 27.7 ± 5.8, 34.6 ± 5.8, 38.4 ± 5.8 [Formula: see text]M, respectively. Further confirmation of the most active derivatives was done through molecular docking analysis, which were found aligned with in vitro study. These potent derivatives can act as lead molecules for further investigation.