Quercetin-3 Sulfate: A Novel Inhibitor Targeting Helicobacter Pylori Revealed through Molecular Docking and Dynamic...

Area of Science:

• Biochemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Type II dehydroquinase (DHQase) is vital for aromatic amino acid synthesis in Helicobacter pylori.
• DHQase has unique characteristics, differing significantly from enzymes in other bacteria.
• Targeting DHQase presents a promising strategy for developing new anti-H. pylori therapies.

Purpose of the Study:

• To identify natural compounds from Middle Eastern medicinal plants that can inhibit H. pylori DHQase.
• To evaluate the binding affinity and drug-like properties of potential DHQase inhibitors.
• To assess the stability and efficacy of the most promising inhibitor through molecular dynamic simulations.

Main Methods:

• Molecular docking was used to screen 2,213 ligand conformers from 151 Middle Eastern medicinal plants against H. pylori DHQase.
• Ten top-scoring compounds underwent ADMET analysis and molecular dynamic simulations.
• Ligand-target interactions and complex stability were analyzed using RMSD and residue contribution metrics.

Main Results:

• Quercetin-3 sulfate exhibited the highest docking score, indicating strong binding affinity to DHQase.
• The compound met druglikeness criteria and showed no predicted toxicity.
• Molecular dynamics simulations confirmed the stable interaction of quercetin-3 sulfate with DHQase, outperforming other candidates.

Conclusions:

• Quercetin-3 sulfate is a novel and potent inhibitor of H. pylori DHQase.
• Its high ligand affinity and favorable pharmacokinetic properties suggest its potential as a therapeutic agent against H. pylori infections.
• This study highlights the value of natural products in discovering new anti-infective drugs.