Development of bis-thiobarbiturates as successful urease inhibitors and their molecular modeling studies

Abstract Bis-thiobarbiturate derivatives 1 – 15 have been synthesized , characterized by 1 HNMR and EI-MS and screened for urease inhibition. All compounds showed various degree of urease inhibitory activity with IC 50 values ranging 7.45 ± 0.12 − 74.24 ± 0.81 μmol/L while the standard thiourea behaved normally (IC 50  = 21.10 ± 0.12). Compounds 1 (IC 50  = 7.45 ± 0.12 μmol/L), 9 (IC 50  = 18.17 ± 1.03 μmol/L) and 13 (IC 50  = 8.61 ± 0.45 μmol/L) showed excellent urease inhibitory activity in the series. Molecular modeling studies were performed to understand the binding site with the bimetallic nickel center of the enzyme. Structure-activity relationship has also been established for these compounds. This study identified bis-thiobarbiturate as a novel class of urease inhibitors.