title: Monoamine Oxidase Inhibitory Activity of Ferulic Acid Amides: Curcumin-Based Design and Synthesis.
abstract: Ferulic acid has structural similarity with curcumin which is being reported for its monoamine oxidase (MAO) inhibitory activity. Based on this similarity, we designed a series of ferulic acid amides 6a-m and tested for their inhibitory activity on human MAO (hMAO) isoforms. All the compounds were found to inhibit the hMAO isoforms either selectively or non-selectively. Nine compounds (6a, 6b, 6g-m) were found to inhibit hMAO-B selectively, whereas the other four (6c-f) were found to be non-selective. There is a gradual shift from hMAO-B selectivity (6a,b) to non-selectivity (6c-f) as there is an increase in chain length at the amino terminus. In case of compounds having an aromatic nucleus at the amino terminus, increasing the carbon number between N and the aromatic ring increases the potency as well as selectivity toward hMAO-B. Compounds 6f, 6j, and 6k were subjected to membrane permeability and metabolic stability studies by in vitro assay methods. They were found to have a better pharmacokinetic profile than curcumin, ferulic acid, and selegiline. In order to understand the structural features responsible for the potency and selectivity of 6k, we carried out a molecular docking simulation study.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Vishnu N
authors.initials: VN
authors.lastname: Badavath
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Ankara, Turkey.
authors.forename: İpek
authors.initials: İ
authors.lastname: Baysal
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Ankara, Turkey.
authors.forename: Gülberk
authors.initials: G
authors.lastname: Uçar
authors.affiliation: TCG Lifesciences Ltd, Block-EP&GP, BIPL, Tower-B, Saltlake, Sector-V, Kolkata, West Bengal, India.
authors.forename: Susanta K
authors.initials: SK
authors.lastname: Mondal
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Barij N
authors.initials: BN
authors.lastname: Sinha
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability; D003373:Coumaric Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008862:Microsomes, Liver / Q000378:metabolism; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D003373:Coumaric Acids; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; C004999:ferulic acid; D008995:Monoamine Oxidase; D003474:Curcumin
keywords: Ferulic acid amides; Metabolic stability studies; Molecular docking; Permeability studies; hMAO inhibitors