Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated...

Area of Science:

• Medicinal Chemistry
• Enzymology
• Biochemistry

Background:

• Urease enzymes are crucial targets for developing pharmaceuticals and agricultural products.
• Benzimidazole-2-thione derivatives are explored for their potential urease inhibitory properties.

Purpose of the Study:

• To design, synthesize, and evaluate novel benzimidazole-2-thione derivatives as urease inhibitors.
• To investigate the inhibitory activity against ureases from Helicobacter pylori and Jack bean.
• To assess the binding modes and safety profiles of potent inhibitors.

Main Methods:

• Recombinant Helicobacter pylori urease isolation and purification using His-tag and FPLC.
• Synthesis and in vitro screening of thirteen benzimidazole-2-thione derivatives.
• Molecular docking studies against H. pylori urease (PDB ID: 1E9Y).
• In silico ADMET prediction and in vitro cytotoxicity assays.

Main Results:

• Compounds 2 and 5 exhibited significant inhibition against both H. pylori and Jack bean ureases, with IC50 values as low as 0.01 mM for compound 5 against H. pylori urease.
• Molecular docking revealed favorable binding modes for compounds 2 and 5 with H. pylori urease, showing binding free energy values of -9.74 and -13.82 kcal/mol, respectively.
• In silico ADMET analysis and in vitro cytotoxicity assays confirmed the safety and drug-likeness of compounds 2 and 5.

Conclusions:

• The synthesized benzimidazole-2-thione derivatives, particularly compounds 2 and 5, are effective inhibitors of both H. pylori and Jack bean ureases.
• Compounds 2 and 5 demonstrate promising therapeutic potential as urease inhibitors due to their potent activity, favorable binding interactions, and safety profiles.
• These findings support the development of novel benzimidazole-2-thione derivatives for pharmacological applications targeting urease activity.