Abstract:
Helicobacter pylori is a pathogenic bacterium that causes ulcers and inflammations in the stomach
lining. This bacterium produces urease enzyme which catalyzes the hydrolysis of urea in the stomach
to carbon dioxide gas and ammonia. Resultant ammonia neutralizes stomach acid and helps H.
pylori to survive and colonize in the acidic environment of the stomach. Therefore, inhibition of
urease is a good strategy for controlling Helicobacter pylori. In this study, a series of 2,3-disubstituted
quinazolinone derivatives was designed and their binding affinities to urease enzyme were studied
using molecular docking. Auto dock GOLD 5.0.3 and Discovery studio v16.1.0.15 software were
used for the computational docking study. In the synthesis, anthranilic acid was reacted with benzoyl
chloride followed by dehydration to form a benzoxazinone intermediate. Subsequent addition of
an amine to the benzoxazinone intermediate provided fused quinazolinone, named 3-amino-2-
phenylquinazolin-4(3H)-one (NE-05). An improved method was developed for the synthesis of
NE-05 in solvent-free conditions. Schiff bases (NE-06, 07, 08) were synthesized by the reaction of
NE-05 with aldehydes benzaldehyde, p-hydroxybenzaldehyde and formaldehyde respectively. The
structures of the synthesized derivatives were confirmed using IR and NMR spectroscopy. In vitro,
urease inhibitory activity of the synthesized compounds was evaluated using modified Berthelot’s
spectrophotometric method. Among the synthesized compounds, NE-05, NE-06, NE-07 and NE-08
showed an inhibitory effect of more than 50%, and among them, NE-06 and NE-07 are the two most
promising compounds
