title: 4-Organoseleno-Isoquinolines Selectively and Reversibly Inhibit the Cerebral Monoamine Oxidase B Activity.
abstract: Isoquinolines are formed endogenously as metabolites of neurotransmitters and are studied because they have structures similar to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and selegiline, a selective inhibitor of MAO-B. This study investigated a possible in vitro inhibitory activity of new 4-organochalcogen-isoquinoline derivatives, containing sulfur 1, selenium 2 or tellurium 3 on MAO-A and B activities. Considering that the non-substituted selenoisoquinoline derivative 2 showed the best inhibitory profile (IC50 = 36.45 μM), new compounds were synthesized by adding substituents (methyl 2a, fluorine 2b, chloro 2c and trifluoromethyl 2d) to the aromatic ring bonded to the selenium atom of compound 2. All tested compounds were selective MAO-B inhibitors, although only the substituted isoquinoline derivative 2b showed IC50 lower than the concentration of 100 μM (IC50 = 82.41 μM). Compounds 2 and 2b were chosen to study the inhibitory profile. These compounds demonstrated reversible and mixed inhibition by decreasing apparent V (app) max and increasing apparent K (app) m, however the non-substituted compound 2 was a more potent inhibitor than the substituted compound 2b (K i = 7.07 and 16.30 μM). In conclusion, selenoisoquinolines 2 and 2b fit in the profile of third generation MAO inhibitors (selective and reversible), which are promising alternatives for treatment of emotional and neurodegenerative disorders.
authors.affiliation: Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.
authors.forename: Tuane Bazanella
authors.initials: TB
authors.lastname: Sampaio
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, 90050-170, Brazil.
authors.forename: Juliana Trevisan
authors.initials: JT
authors.lastname: Da Rocha
authors.affiliation: Universidade Federal do Pampa - Campus Itaqui, Itaqui, Rio Grande do Sul, 97650-000, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: Prigol
authors.affiliation: Universidade Federal Rural de Pernambuco - Unidade Acadêmica de Serra Talhada, Serra Talhada, Pernambuco, 56903-000, Brazil.
authors.forename: Rogério Aquino
authors.initials: RA
authors.lastname: Saraiva
authors.affiliation: Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.
authors.forename: Pablo Froner
authors.initials: PF
authors.lastname: Nogara
authors.affiliation: Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.
authors.forename: André Luiz Agnes
authors.initials: AL
authors.lastname: Stein
authors.affiliation: Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.affiliation: Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, 97105-900, Brazil.
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
authors.affiliation: Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, 97105-900, Brazil. criswn@ufsm.br.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D007546:Isoquinolines / Q000737:chemistry*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D016566:Organoselenium Compounds; D008995:Monoamine Oxidase
keywords: Isoquinoline; Kinetics profile; MAO (MAO-B) inhibitors; Organochalcogen; Selenium