Hydrazine clubbed 1,3-thiazoles as potent urease inhibitors: design, synthesis and molecular docking studies

Synthesis of a novel series of hydrazine clubbed 1,3-thiazoles ( 5a–m ) has been described by reacting hydrazine-1-carbothioamides ( 3a–k ) with α -chloro- or bromo-acetophenones ( 4a–d ) in refluxing ethanol in good to excellent yields (65–86%). Structural confirmation was based upon spectroscopic techniques such as 1 H-NMR, 13 C-NMR, FT-IR and mass spectrometry. The biological application of these motifs has been demonstrated in terms of their strong urease inhibition activity. The results of in vitro study revealed that all the compounds are the potent inhibitors of urease. The IC 50 (ranging in between 110 and 440 nM) values were higher as compared to that of standard, i.e., thiourea (IC 50 = 490 ± 10 nM). The synthesized compounds were docked at the active sites of the Jack bean urease enzyme in order to explore the possible binding interactions of enzyme–ligand complexes; the results reinforced the in vitro biological activity results. Graphic abstract