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

Bis-thiobarbiturate derivatives 1-15 have been synthesized, characterized by ¹HNMR and EI-MS and screened for urease inhibition. All compounds showed various degree of urease inhibitory activity with IC₅₀ values ranging 7.45±0.12-74.24±0.81 μmol/L while the standard thiourea behaved normally (IC₅₀=21.10±0.12). Compounds 1 (IC₅₀=7.45±0.12 μmol/L), 9 (IC₅₀=18.17±1.03 μmol/L) and 13 (IC₅₀=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 bisthiobarbiturate as a novel class of urease inhibitors.