Isoindolin-1-ones Fused to Barbiturates: From Design and Molecular Docking to Synthesis and Urease Inhibitory Evaluation

Helicobacter
pylori-induced ulcers
and gastric cancer have been one of the main obstacles that the human
community has ever struggled with, especially in recent decades. Several
different attempts have been made to eradicate this group. One of
the most widely used attempts is to inhibit the critical enzyme that
facilitates its survival, the urease enzyme. Therefore, in this study,
isoindolin-1-ones fused to barbiturates were designed, synthesized,
and evaluated for their in vitro urease inhibitory activity as novel
inhibitors for the urease enzyme. The synthesis route consisted of
two steps. These steps increased the yield rate and decreased the
percentage of byproducts while approaching green chemistry using ethanol
and water as green solvents and microwave irradiation instead of conventional
methods. In vitro urease inhibitory results indicated that all the
compounds had higher inhibitory activity than the standard inhibitor,
thiourea, and compound 5b proved to be the most potent
inhibitor (IC50 = 0.82 ± 0.03 μM). A molecular
docking study was performed to understand the interaction between
compounds 5a–n and Jack bean urease enzyme. The
results of the molecular docking study were also in harmony with the
in vitro results, which are discussed in detail later in this study.