Virtual screening for novel COX-2 inhibitors using the ZINC database

Area of Science:

• Medicinal Chemistry
• Computational Drug Discovery
• Pharmacology

Background:

• Cyclooxygenase-2 (COX-2) inhibitors are used to reduce inflammation but can cause cardiovascular and gastrointestinal issues.
• Existing COX-2 inhibitors lack anti-thrombotic activity, necessitating the development of safer alternatives.
• There is a continuous need for novel COX-2 inhibitors with improved efficacy and safety profiles.

Purpose of the Study:

• To identify novel, potent COX-2 inhibitors through virtual screening of the ZINC database.
• To discover compounds with favorable binding interactions within the COX-2 active site.
• To find potential drug candidates with reduced liabilities compared to existing COX-2 inhibitors.

Main Methods:

• Virtual screening of the ZINC database using eHiTS software against the COX-2 protein.
• Filtering compounds based on physico-chemical properties similar to the known ligand SC-558.
• Molecular docking and scoring of filtered compounds to assess binding affinity and mode.

Main Results:

• Identified two potential COX-2 inhibitors, ZINC00663976 and ZINC02062094, from the ZINC database.
• Both identified compounds exhibited superior eHiTS scores compared to the co-crystallized ligand SC-558.
• Docking analysis revealed favorable interactions within the COX-2 binding pocket, including hydrogen bonding for ZINC02062094.

Conclusions:

• The virtual screening approach successfully identified novel compounds with potential COX-2 inhibitory activity.
• ZINC00663976 and ZINC02062094 represent promising leads for developing next-generation COX-2 inhibitors.
• Further experimental validation is warranted to confirm the therapeutic potential of these identified compounds.