Inhibition of monoamine oxidase by indole-5,6-dicarbonitrile derivatives

An investigation of the monoamine oxidase inhibition properties of pyrrolo[3,4‐f]indole‐5,7‐dione and indole‐5,6‐dicarbonitrile derivatives

“…To allow for comparison of the inhibition potencies, the MAO inhibition properties of the test inhibitors were determined according the same protocol and conditions as the literature pyrrolo[3,4‐ f ]indole‐5,7‐dione and indole‐5,6‐dicarbonitrile derivatives (Chirkova et al, ). The recombinant human MAOs served as enzyme sources and kynuramine as substrate for both MAO isoforms (Novaroli et al, ).…”

“…It was recently shown that phthalimide and nitrile compounds are highly potent and specific MAO‐B inhibitors, with for example compounds 1 and 2 exhibiting IC 50 values for the inhibition of human MAO‐B of 0.0069 and 0.0048 µM, respectively (Figure ) (Manley‐King, Bergh, & Petzer, ). In subsequent studies it was shown that series of pyrrolo[3,4‐ f ]indole‐5,7‐dione and indole‐5,6‐dicarbonitrile derivatives act as good potency in vitro inhibitors of the MAO enzymes (Chirkova et al, ). For example, pyrrolo[3,4‐ f ]indole‐5,7‐dione derivative 3 inhibits MAO‐A with an IC 50 value of 0.250 µM while indole‐5,6‐dicarbonitrile 4 inhibits MAO‐A and MAO‐B with IC 50 values of 0.014 and 0.017 µM, respectively.…”

Monoamine oxidase‐B inhibitors as potential neurotherapeutic agents: An overview and update

“…Phthalonitriles ( 109‐110 ), indole‐5,6‐dicarbonitriles ( 111‐114 ), pyrrolo[3,4‐f]indole‐5,7‐dione ( 115 ), and dicarboxylic acids (116 ) . hMAO, human monoamine oxidase; IC 50 , half maximal inhibitory concentration…”

“…Based on the above findings, to explore chemical space and potentially discover phthalonitrile‐derived MAO‐B inhibitors, Chirkova et al synthesized several indole‐5,6‐dicarbonitrile derivatives from the corresponding 1‐hydroxy‐1 H ‐indole‐5,6‐dicarbonitrile derivatives and evaluated them for MAO‐B inhibitory activity (Figure ). The results evidenced that certain indole‐5,6‐dicarbonitrile derivatives proved to be significant inhibitors, with good potencies recorded for the inhibition of MAO‐B isoform.…”

Synthesis of some novel 2-substituted benzothiazole derivatives containing benzylamine moiety as monoamine oxidase inhibitory agents

“…By means of their regulatory effect on the metabolism of neurotransmitters, MAOs are increasingly becoming an important area in medicinal chemistry. MAO-A inhibitors are clinically used mostly as antidepressants 11,12 , whereas MAO-B inhibitors are generally used in dealing with symptoms associated with Parkinson's and Alzheimer's diseases 13,14 . Iproniazid is the first drug used in the therapy of depressive disorder during 1950s 15 .…”