Novel N,N-dimethylbarbituric-pyridinium derivatives as potent urease inhibitors: Synthesis, in vitro, and in silico studies

Abstract

A new series of N,N-dimethylbarbituric-pyridinium derivatives 7a-n was synthesized and evaluated as Helicobacter pylori urease inhibitors. All the synthesized compounds (IC₅₀ = 10.37 ± 1.0-77.52 ± 2.7 μM) were more potent than standard inhibitor hydroxyurea against urease (IC₅₀ = 100.00 ± 0.2 μM). Furthermore, comparison of IC₅₀ values of the synthesized compounds with the second standard inhibitor thiourea (IC₅₀ = 22.0 ± 0.03 µM) revealed that compounds 7a-b and 7f-h were more potent than thiourea. Molecular modeling study of the most potent compounds 7a, 7b, 7f, and 7g was also conducted. Additionally, the drug-likeness properties of the synthesized compounds, based on Lipinski rule and other filters, were evaluated.

Keywords: Barbituric acid; Helicobacter pylori; Molecular docking; N,N-dimethylbarbituric; Urease inhibitor.