Synthesis and structure–activity relationship of thiobarbituric acid derivatives as potent inhibitors of urease

Abstract

A series of thiobarbituric acid derivatives 1–27 were synthesized and evaluated for their urease inhibitory potential. Exciting results were obtained from the screening of these compounds 1–27. Compounds 5, 7, 8, 11, 16, 17, 22, 23 and 24 showed excellent urease inhibition with IC50 values 18.1±0.52, 16.0±0.45, 16.0±0.22, 14.3±0.27, 6.7±0.27, 10.6±0.17, 19.2±0.29, 18.2±0.76 and 1.61±0.18μM, respectively, much better than the standard urease inhibitor thiourea (IC50=21±0.11μM). Compound 3, 4, 10, and 26 exhibited comparable activities to the standard with IC50 values 21.4±1.04 and 21.5±0.61μM, 22.8±0.32, 25.2±0.63, respectively. However the remaining compounds also showed prominent inhibitory potential The structure–activity relationship was established for these compounds. This study identified a novel class of urease inhibitors. The structures of all compounds were confirmed through spectroscopic techniques such as EI-MS and 1H NMR.