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

• Published in: Chinese Chemical Letters
• Main Author: Rahim F.; Ali M.; Ullah S.; Rashid U.; Ullah H.; Taha M.; Javed M.T.; Rehman W.; Khan A.A.; Abid O.U.R.; Bilal M.
• Format: Article
• Language: English
• Published: Elsevier 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84960192729&doi=10.1016%2fj.cclet.2015.12.035&partnerID=40&md5=811cfe660bde2a5cdcd83e2b4571e983
• ISSN: 10018417
• DOI: 10.1016/j.cclet.2015.12.035

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. © 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.