Methoxyphenol derivatives as reversible inhibitors of myeloperoxidase as potential antiatherosclerotic agents

To evaluate new chemical entities, based on ferulic acid scaffolds, as reversible myeloperoxidase inhibitors (MPOI). docking studies are performed with MPO protein as a target for several ferulic acid analogs followed by multiple assays to validate this approach. Two lead compounds and are identified with optimum docking and IC values: -7.95 kcal/mol, 0.9 μM and -8.35 kcal/mol, 8.5 μM, respectively. These MPOIs are able to inhibit oxidation of high-density lipoprotein and further promoted functionality of high-density lipoprotein. Lead analogs are potent MPOIs that exert specific effects on MPO-mediated oxidation as well as inflammatory pathways. It also acts as promoters of cholesterol efflux that sheds light on pharmacological approach in atherosclerosis treatment.