title: Quantum chemical modeling of the inhibition mechanism of monoamine oxidase by oxazolidinone and analogous heterocyclic compounds.
abstract: Monoamine oxidase (MAO, EC 1.4.3.4) is responsible from the oxidation of a variety of amine neurotransmitters. MAO inhibitors are used for the treatment of depression or Parkinson's disease. They also inhibit the catabolism of dietary amines. According to one hypothesis, inactivation results from the formation of a covalent adduct to a cysteine residue in the enzyme. If the adduct is stable enough, the enzyme is inhibited for a long time. After a while, enzyme can turn to its active form as a result of adduct breakdown by β-elimination. In this study, the proposed inactivation mechanism was modeled and tested by quantum chemical calculations. Eight heterocyclic methylthioamine derivatives were selected to represent the proposed covalent adducts. Activation energies related to their β-elimination reactions were calculated using ab initio and density functional theory methods. Calculated activation energies were in good agreement with the relative stabilities of the hypothetical adducts predicted in the literature by enzyme inactivation measurements.
authors: Chemistry Department, Faculty of Arts and Sciences, Marmara University , Istanbul , Turkey and.
authors: Safiye Sağ
authors: SS
authors: Erdem
authors: Gül Altınbaş
authors: GA
authors: Özpınar
authors: Ümüt
authors: Ü
authors: Boz
mesh_terms: D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry*; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory
chemical_list: D006571:Heterocyclic Compounds; D008996:Monoamine Oxidase Inhibitors; D023303:Oxazolidinones