title: Potent and Selective Monoamine Oxidase-B Inhibitory Activity: Fluoro- vs. Trifluoromethyl-4-hydroxylated Chalcone Derivatives.
abstract: For various neurodegenerative disorders like Alzheimer's and Parkinson's diseases, selective and reversible MAO-B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase-B (hMAO-B). In continuation of our earlier study and to extend the understanding of the structure-activity relationships, a series of five new chalcones were studied for their inhibition of hMAO. The results demonstrated that these compounds are reversible and selective hMAO-B inhibitors with a competitive mode of inhibition. The most active compound, (2E)-1-(4-hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one, exhibited a Ki value of 0.33 ± 0.01 μm toward hMAO-B with a selectivity index of 26.36. A molecular docking study revealed that the presence of a H-bond network in hydroxylated chalcone with the N(5) atom of FAD is crucial for MAO-B selectivity and potency.
authors.affiliation: Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, 678557, Kerala, India. bijovilaventgu@gmail.com.
authors.forename: Bijo
authors.initials: B
authors.lastname: Mathew
authors.affiliation: Department of Pharmacology, Grace College of Pharmacy, Palakkad, 678004, Kerala, India.
authors.forename: Githa Elizabeth
authors.initials: GE
authors.lastname: Mathew
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, TR-06100, Ankara. gulberk@hacettepe.edu.tr.
authors.forename: Gülberk
authors.initials: G
authors.lastname: Uçar
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, TR-06100, Ankara.
authors.forename: Ipek
authors.initials: I
authors.lastname: Baysal
authors.affiliation: Department of Pharmaceutical Chemistry, Madras Medical College, 600004, Chennai, India.
authors.forename: Jerad
authors.initials: J
authors.lastname: Suresh
authors.affiliation: Department of Pharmacology, Grace College of Pharmacy, Palakkad, 678004, Kerala, India.
authors.forename: Sincy
authors.initials: S
authors.lastname: Mathew
authors.affiliation: Department of Pharmacology, Grace College of Pharmacy, Palakkad, 678004, Kerala, India.
authors.forename: Abitha
authors.initials: A
authors.lastname: Haridas
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835 215, India.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
mesh_terms: D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase
keywords: Chalcone; MAO-A; MAO-B; Molecular docking