A piggyback or drug repositioning approach to drug discovery and development was applied in finding potential inhibitors ofenoyl reductase (InhA), an enzyme involved in fatty acid and cell wall synthesis of M. tuberculosis. The questsprang from entacapone, a drug for Parkinson’s disease, which was also found to inhibit InhA enzyme. A compound database was scoured to search for entacapone-like structures, which were then filtered based on LibDock scores. The hits were subsequently docked into InhA binding site by the use of CDocker protocol and their binding energies were calculated. The results showed that the dimer, and an alcohol and piperazine derivatives of entacapone are potential inhibitors of InhA. H-bonding and p-p interactions with nicotinamide adenine dinucleotide(NAD) at the binding pocket are salient features in binding interactions. Interestingly, the four entacapone analogues exhibited greater binding affinity with InhA compared to entacapone itself and the native ligand,5-pentyl-2-phenoxyphenol.