title: Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies.
abstract: A series of methoxylated chalcones with fluoro and trifluoromethyl derivatives were synthesized and investigated for their ability to inhibit human monoamine oxidase A and B. The chemical structures of the compounds have been characterized by means of their (1)H NMR, (13)C NMR, Mass spectroscopic datas and elemental analysis. The results demonstrate that these compounds are reversible and selective MAO-B inhibitors with a competitive mode of inhibition. The most potent compound (2E)-1-(4-methoxyphenyl)-3-[4-(trifluoromethyl)phenyl] prop-2-en-1-one showed the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.22±0.01μM and 0.05 comparable to that standard drug, Selegiline Ki and SI values were found as 0.33±0.03μM and 0.04, respectively. Molecular docking studies were carried out to further explain the in vitro results of the new compounds, and to identify the hypothetical binding mode for the compounds inside the inhibitor binding cavity of hMAO-B.
authors.affiliation: Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad 678004, Kerala, India. Electronic address: 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, 06100 Sıhhiye, Ankara, Turkey.
authors.forename: Gülberk
authors.initials: G
authors.lastname: Uçar
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sıhhiye, Ankara, Turkey.
authors.forename: Ipek
authors.initials: I
authors.lastname: Baysal
authors.affiliation: Department of Pharmaceutical Chemistry, Madras Medical College, Chennai 600004, India.
authors.forename: Jerad
authors.initials: J
authors.lastname: Suresh
authors.affiliation: Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad 678004, Kerala, India.
authors.forename: Jobin Kunjumon
authors.initials: JK
authors.lastname: Vilapurathu
authors.affiliation: Department of Pharmacology, Grace College of Pharmacy, Palakkad 678004, Kerala, India.
authors.forename: Aneesh
authors.initials: A
authors.lastname: Prakasan
authors.affiliation: Department of Pharmacology, Grace College of Pharmacy, Palakkad 678004, Kerala, India.
authors.forename: Jeethu Kuruppath
authors.initials: JK
authors.lastname: Suresh
authors.affiliation: Department of Pharmacology, Grace College of Pharmacy, Palakkad 678004, Kerala, India.
authors.forename: Anjana
authors.initials: A
authors.lastname: Thomas
mesh_terms: D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C000607264:1-(4-methoxyphenyl)-3-(4-(trifluoromethyl)phenyl)prop-2-en-1-one; D047188:Chalcones; D006845:Hydrocarbons, Fluorinated; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; D011407:Propane
keywords: MAO-A; MAO-B; Methoxylated chalcone; Molecular docking