Background: Urease enzyme catalyzes the hydrolysis of urea into ammonia and CO2,
excess ammonia causes global warming and crop reduction. Ureases are also responsible for certain
human diseases such as stomach cancer, peptic ulceration, pyelonephritis, and kidney stones.
New urease inhibitors are developed to get rid of such problems.
Objective: This article describes the synthesis of a series of novel 1-aroyl-3-(2-oxo-2H-chromen-4-
yl)thiourea derivatives (5a-j) as Jack bean urease inhibitors.
Methods: Freshly prepared aryl isothiocyanates were reacted with 4-aminocoumarin in the same
pot in an anhydrous medium of acetone. The structures of the title thioureas (5a-j) were ascertained
by their spectroscopic data. The inhibitory effects against jack bean urease were determined.
Results: It was found that compounds 5i and 5j showed excellent activity with IC50 values 0.0065
and 0.0293, µM respectively. Compound 5i bearing 4-methyl substituted phenyl ring plays a vital
role in enzyme inhibitory activity. The kinetic mechanism analyzed by Lineweavere-Burk plots
revealed that compound 5i inhibits the enzyme non-competitively. The Michaelis-Menten constant
Km and inhibition constants Ki calculated from Lineweavere-Burk plots for compound 5i are
4.155mM and 0.00032µM, respectively. The antioxidant activity results displayed that compound
5j showed excellent radical scavenging activity. The cytotoxic effects determined against brine
shrimp assay showed that all of the synthesized compounds are non-toxic to shrimp larvae. Molecular
docking studies were performed against target protein (PDBID 4H9M) and it was determined
that most of the synthesized compounds exhibited good binding affinity with the target protein.
Molecular dynamics simulation (MDS) results revealed that compound 5i forms a stable
complex with target protein showing little fluctuation.
Conclusions: Based upon our investigations, it is proposed that 5i derivative may serve as a lead
structure for devising more potent urease inhibitors.