In search of novel anti-inflammatory agents: Computational repositioning of approved drugs

•The present study describes an application of computational drug repositioning for anti-inflammatory indication. Using a set of three query molecules (diclofenac, celecoxib and a potent mPGES-1 inhibitor) acting on different targets in the PG biosynthetic pathway, shape- and electrostatics-based virtual screening was performed on a database of approved small molecule drugs.•Detailed literature search of the top 100 hits from each of the lists led to interesting reports wherein the hits were found to exhibit anti-inflammatory activity. This validated the repurposing hypothesis generated using the computational analyses.•Experimental evaluations of few of these hits in target-specific or phenotypic assays may yield useful starting points either for drug repositioning or drug discovery.•Such interesting investigations and the finding therein may advance our knowledge of the therapeutic area, in general.

Computational drug repositioning is a powerful tool to guide the experimental drug repositioning campaigns. Both structure-based (e.g., reverse docking) and ligand-based (e.g., 3D pharmacophore) approaches can be used for the generation of repurposing hypotheses. In an attempt to discover novel anti-inflammatory agents, computational repurposing of approved small molecule drugs was undertaken using diclofenac (nonselective cyclooxygenase (COX) inhibitor), celecoxib (selective COX-2 inhibitor) and a potent microsomal prostaglandin E synthase – 1 (mPGES-1) inhibitor as query molecules for shape- and electrostatics-based virtual screening. Several approved drugs (other than anti-inflammatory) were amongst the top 5% of the hits. These hits (approved drugs) may serve as starting points for clinical repositioning (anti-inflammatory indication) or as lead structures in drug discovery programs.