In vitro inhibition of Helicobacter pylori, interaction studies and molecular docking of lichen natural products with jack bean urease

Compounds able to inhibit the activity of H. pylori urease have been used for treatment of diseases associated with infections caused by this bacterium. Then, the development of urease inhibitors has been an interesting approach for the treatment of H. pylori-associated diseases1. This work focused on the in vitro evaluation of the inhibitor potential of lichen secondary metabolites like usnic acid isomers [(S)-(-)-UA and (R)-(+)-UA] and fumarprotocetraric acid (FUM) through of kinetics and spectroscopic studies with jack bean at pH 7.4. All lichen compounds tested interact with urease by statistic quenching mechanism and change the native protein structure. The complexes were mainly stabilized by electrostatic forces and according Kb values to the following order of affinity: (R)-(+)-UA > (S)-(-)-UA > FUM. The (S)-(-)-UA, acts as mixed inhibitor while (R)-(+)-UA and FUM are competitive ones. Moreover, minimum inhibitory concentrations for the lichen metabolites tested were lower (from 2- to 7.8-fold) than those of omeprazole against five H. pylori strains tested. Finally, we explored the binding mode of the isomers in the active site of jack bean and H. pylori ureases (Fig. 1), using docking molecular. The (R)-(+)-UA isomer showed stronger interaction in the active site with both ureases evaluated. The docking results indicate that the (R)-(+)-UA showed better binding affinity than (S)-(-)-UA corroborating with experimental results. Overall, the lichen metabolites tested are lead compounds for the design of more efficient urease inhibitors for the treatment of H. pylori infections