Identification Of New Cyclooxygenase-2 Selective Inhibitors Via Virtual Screening And Complex-Based Pharmacophore Mapping

Original Article

Abstract

Background: New and effective COX-2-targeted medications may cure cancer, inflammation, and other disorders.
It’s difficult to produce druggable site inhibitors for target protein inhibition that are strong and selective. Such medications need a more informed structure-based or ligand-based drug discovery technique. MOE was used to create a
six-point COX-2 selective inhibitor pharmacophore from 43 compounds. The structure includes three aromatic rings,
one hydrophobic group (Hyd), one donor (Don), and three H-bond acceptors. A pharmacophore was used to digitally
filter the Chembridge database to locate additional structural poses that fulfilled the model’s requirements. We found
2090 structurally diverse hits after filtering. Molecular docking was performed on 767 hits after Lipinski’s rule of five
determined druggability. Twenty compounds with high active site amino acid residue interactions and diverse scaffolds
were chosen. The first COX-2 isoform-inhibiting medicines were discovered using structure-based pharmacophores.
Objectives Using complex-based pharmacophore mapping and virtual screening, this research seeks novel selective
COX-2 inhibitors. This involves filtering through a chemical database, defining critical interactions, maximizing hits,
and extending drug development for safer and more effective inflammation and pain managem
Study design : Employing Advanced Computational And Pharmacological Approaches Study
Duration and place of study :The study was conducted at Abdul Wali Khan University Mardan from jan
2017 to jan 2018
Methods: The investigation used a structure-based drug discovery methodology to find novel cyclooxygenase-2 (COX-2)
selective inhibitors. The COX-2 crystal structure was used to create a pharmacophore model, which was then used to
virtually search a chemical database. In order to identify potential lead compounds based on interactions with important
COX-2 residues, binding energies were computed, and molecular docking was used to refine hits.
Results: The goal of the project was to use virtual screening and complex-based pharmacophore mapping to find
novel selective COX-2 inhibitors. After the COX-2 crystal structure was used to create a pharmacophore model,
2090 hits were discovered in a database. Following the druggability assessment, 767 hits were chosen for molecular
docking. Ultimately, twenty compounds were found to be promising COX-2 inhibitors due to their strong interactions
with COX-2 and variety of scaffolds.
Conclusion: This study found 20 possible lead drugs that selectively block cyclooxygenase-2 (COX-2) using complex-based pharmacophore mapping and virtual screening. These substances show a variety of scaffolds and robust
interactions with COX-2, making them attractive candidates for further research and development as anti-inflammatory
and anti-cancer medications with maybe fewer adverse effects.
Keywords: Cyclooxygenase-2 (COX-2),Pharmacophore mapping,Virtual screening,Drug discovery