Background: Helicobacter pylori is a gram-negative bacterium related to chronic gastritis, peptic
ulcer and gastric carcinoma. During its infection process, promotes excessive inflammatory response, increasing
the release of reactive species and inducing the production of pro-inflammatory mediators. Inducible Nitric
Oxide Synthase (iNOS) plays a crucial role in the gastric carcinogenesis process and a key mediator of inflammation
and host defense systems, which is expressed in macrophages induced by inflammatory stimuli. In
chronic diseases such as Helicobacter pylori infections, the overproduction of NO due to the prolonged induction
of iNOS is of major concern.
Objectives: In this sense, the search for potential iNOS inhibitors is a valuable strategy in the overall process
of Helicobacter pylori pathogeny.
Methods: In silico techniques were applied in the search of interesting compounds against Inducible Nitric
Oxide Synthase enzyme in a chemical space of natural products and derivatives from the Analyticon Discovery
Results: The five compounds with the best iNOS inhibition profile were selected for activity and toxicity predictions.
Compound 9 (CAS 88198-99-6) displayed significant potential for iNOS inhibition, forming hydrogen
bonds with residues from the active site and an ionic interaction with heme. This compound also displayed
good bioavailability and absence of toxicity/or from its probable metabolites.
Conclusion: The top-ranked compounds from the virtual screening workflow show promising results regarding
the iNOS inhibition profile. The results evidenced the importance of the ionic bonding during docking selection,
playing a crucial role in binding and positioning during ligand-target selection for iNOS.