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 bis-thiobarbiturate as a novel class of urease inhibitors.

Graphical abstractWe have synthesized bis-thiobarbiturate derivatives 1–15, which were screened against the urease enzyme. All compounds showed various degree of urease inhibitory activity. Compound 1 (IC50 = 7.45 ± 0.12 μmol/L) was the most active in the series.Figure optionsDownload full-size imageDownload as PowerPoint slide