Discovery of antiadhesins of Helicobacter pylori from existing drugs and medicines for malaria ventures pathogen box compounds

Abstract

Background: Helicobacter pylori infection is a worldwide problem with more than half of the world's population in both developed and developing countries are infected with this organism. The best-characterized H. pylori adhesins, Blood group antigen binding Adhesin (BabA) and Sialic acid binding Adhesin (SabA) are virulent factors which facilitate adhesion of the bacteria to the host cells. Methods: We determined the binding affinities of selected existing drugs and medicines for malaria venture pathogen box compounds to H. pylori adhesin receptors by molecular docking simulations. The 3D crystal structures of H. pylori adhesin receptors were obtained from Protein Data Bank (PDB). The receptors were prepared for molecular docking simulations using PyMol 1.3, Chimera 1.9 and AutoDock tools 1.5.6. The 3D structures of the selected existing drugs and Medicines for Malaria Ventures (MMV) pathogen box compounds were obtained from ZINC and PubChem databases. They were prepared for molecular docking simulations using AutoDock tools 1.5.6. Docking protocols were validated by reproducing the PDB crystal structures in silico. Molecular docking simulations were executed with a virtual screening script using AutoDock Vina 1.1.2 on a Linux platform. Results: Entacapone, sildenafil, gemcitabine, tolcapone, rabeprazole, tolazamide, teriflunomide, sulfamethazine, cefotetan, talbutal, mitotane, tolbutamide, piperazine showed higher average binding affinities than the reference compound nitazoxanide molecular dynamics of one front runner with the reference ligand and protein were done at 1000 ps. Rabeprazole showed lower stability than the reference drug after molecular dynamics simulation. Conclusion: The identified existing drugs from molecular docking simulations with higher average binding affinities are predicted as possible H. pylori multi-target antiadhesins.