4-Organoseleno-Isoquinolines Selectively and Reversibly Inhibit the Cerebral Monoamine Oxidase B Activity

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 (IC 50 = 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 IC 50 lower than the concentration of 100 μM (IC 50 = 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.