Discovery of New Inhibitors of Urease Enzyme: A Study Using STD-NMR Spectroscopy

Identification of compounds which can inhibit the activity of urease enzyme is an important approach towards the treatments of peptic ulcer, urolithiasis, and other urease associated disorders. This manuscript describes the in vitro urease inhibitory activity of different derivatives of phenols, heterocyclic compounds, thiols, quinone, tosylphenyl alanine, sulfonyl cyanides, phenyl acetoacetate, and thiamines (1-14). Among them, compounds 10 (IC50 = 12.40 +/- 1.57 mu M), 8 (IC50 = 21.0 +/- 1.16 mu M), and 9 (IC50= 24.94 +/- 1.13 mu M) were identified as potent inhibitors of urease enzyme, more active than the standard drug acetohydroxamic acid (IC50= 41.5 +/- 1.50 mu M). All active compounds were found to be non-cytotoxic against fibroblast cell line (3T3 cell line). All potent compounds were also subjected to the mechanistic studies, as well as ligand-binding by employing STD-NMR spectroscopy. In brief, this mechanism-based study identified potent inhibitors of urease enzyme in vitro as leads for further research.