Designing and docking studies of imidazole-based drugs as potential inhibitors of myeloperoxidase (MPO) mediated inflammation and oxidative stress

164 imidazole-based drugs were designed and their structures were optimized with DFT method. The drugs were screened for drug-likeness using SWISS-ADME server and molecular docking analysis were carried out with MOE 09. The designed drugs were docked with Human Myeloperoxidase (pdb ID: 1DNU ), an active enzyme involved in the cause of inflammation and oxidative stress . The docking analysis identified ligands 154, 158 and 136 as the top three scoring ligand with a binding score of −7.1329 kcal/mol, −7.0021 kcal/mol and −6.9100 kcal/mol respectively. These scores are comparatively better than the selected reference drugs primaquine (−6.3856 kcal/mol) and salicylhydroxamic acid (−4.5722 kcal/mol). The imidazole ring in the drugs contributes to its binding energy through its interaction with the amino acid residue PHE (Phenylalanine) A:99, an important residue of the hydrophobic pocket in the target protein. The interactions of the top scoring ligands with the ARG C:239 and the Porphyrin rings suggest that the designed drugs can act as inhibitors of MPO in competing with H 2 O 2 binding site. • Design and docking studies of imidazole-based drugs as potential human myeloperoxidase inhibitor. • The designed drugs interacts with the amino acid residue PHE A:99, a crucial residue in the hydrophobic pocket. • Drugs with –OH and –OCH 3 substituent groups increases its binding affinity for the target protein. • The drugs interacts with ARG C:239 and the Porphyrin rings, and can be expected to compete with H 2 O 2 binding site.