Future Medicinal Chemistry · 2019 · 17 citations · 39 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructure-activity RelationshipsAntioxidant DefenseEnzyme InhibitionHit-to-lead OptimizationLead Compound DesignLead DiscoveryNatural Product Drug DiscoveryCholesterol EffluxDocking StudiesHigh-density Lipoprotein MetabolismInflammatory Mediator PathwaysInflammatory Oxidative PathwaysLead Compound ScreeningLead ScaffoldsPharmacological Screening
Aim: To evaluate new chemical entities, based on ferulic acid scaffolds, as reversible myeloperoxidase inhibitors (MPOI). Methodology & results: In silico docking studies are performed with MPO protein as a target for several ferulic acid analogs followed by multiple in vitro assays to validate this approach. Two lead compounds 2a and 3 are identified with optimum docking and IC50 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. Conclusion: 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.
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S K Basu, J L Goldstein, Gary Anderson et al. · Proceedings of the National Academy of Sciences · 1976 · 1K citations · Full text