Abstract
Bis-thiobarbiturate derivatives 1-15 have been synthesized, characterized by 1HNMR and El -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 mu mol/L, while the standard thiourea behaved normally (IC50 = 21.10 +/- 0.12). Compounds 1 (IC50 = 7.45 0.12 mu mol/L), 9 (IC50 =18.17 +/- 1.03 mu mol//L) and 13 (IC50 = 8.61 +/- 0.45 mu mol/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. (C) 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.