In Silico investigation of vitamins and their derivatives compounds as potential therapeutic agents on Helicobacter pylori using molecular docking against urease.
In Silico investigation of vitamins and their derivatives compounds as potential therapeutic agents on Helicobacter pylori using molecular docking against urease.
Vajiheh Eskandari,1,*
1. Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran
Introduction: Urease is an enzyme exploited by Helicobacter pylori to infect the highly acidic human stomach. Clinically used drugs are associated with many side effects; therefore, there is a need for less harmful and preferably natural compounds an alternative drug to treat Helicobacter pylori infection. The aim of this study was to investigate vitamins and their derivatives (47 molecules) as urease inhibitors of H. pylori.
Methods: The crystal structures of Urease (PDB ID. 1e9y) was obtained from the Protein Data Bank and after a cleaning with Discovery Studio 4.1, minimized and changed to pdbqt format using MGLTools. 47 FDA approved vitamins were retrieved from Selleckchem Inc web site. The 3D structure of the ligands were retrieved from PubChem database in SDF file format and converted pdbqt format using MGLTools .Then, the ligands were evaluated as inhibitors on important residues of the urease enzyme by Autodock Vina and Autodock 4 in pyRx program and AutoDock Vina software, and the output results were analyzed and evaluated using soft Discovery Studio software.
Results: The results of molecular docking indicated that the vitamins exhibited powerful inhibitory activity against the urease enzyme of H. pylori. The most negative binding energies are observed for the compounds; Ergosterol with Binding energy -9.5, Riboflavin (Vitamin B2) with Binding energy -9.2, Trolox with Binding energy -9.0, Vitamin D3 with Binding energy -8.8, Doxercalciferol with Binding energy -8.8, Calcipotriene with Binding energy -8.7, Vitamin K1 with Binding energy -8.0 and Folic Acid with Binding energy -8.
The results of molecular docking studies indicate that residues; His136, His138, Ala169, KCX219, His221, His248, Asp362 (some of which are part of the active site of the urease and also some of which are nevertheless involved in hydrogen bonding with substrate) bind to above mentioned ligands with best binding energy.
Molecular Dynamic simulation showed that Trolox and Ergosterol are quite stable in binding to urease, therefore they could be valuable repurpose drugs for inhibiting urease activity of helicobacter pylori.
Conclusion: The present findings indicated the inhibitory potential of the Trolox, Ergostero, Riboflavin, Vitamin D3, Doxercalciferol, Calcipotriene, Vitamin K1 and Folic Acid.