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dc.contributor.authorChirkova, Zhanna V.
dc.contributor.authorPetzer, Anél
dc.contributor.authorPetzer, Jacobus P.
dc.contributor.authorKabanova, Mariya V.
dc.contributor.authorFilimonov, Sergey I.
dc.identifier.citationChirkova, Z.V. et al. 2015. Inhibition of monoamine oxidase by indole-5,6-dicarbonitrile derivatives. Bioorganic & medicinal chemistry letters, 25(6):1206-1211. []en_US
dc.identifier.issn1464-3405 (Online)
dc.description.abstractRecent studies have found that phthalonitrile derivatives are remarkably potent inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to further determine the structure-activity relationships (SARs) for MAO inhibition by this class of compounds and to discover novel potent MAO inhibitors, the present study investigated the MAO inhibition properties of a series consisting of indole‐5,6‐dicarbonitrile derivatives. The results document that 3‐chloro‐1H‐indole‐5,6‐dicarbonitrile derivatives exhibited potent inhibition of the MAOs. For example, 3‐chloro‐2‐(4‐methylphenyl)‐1H‐indole‐5,6‐dicarbonitrile inhibited MAO-A and MAO-B with IC50 values of 0.014 μM and 0.017 μM, respectively. It was further shown that this compound acts as a reversible and competitive inhibitor of both MAO isoforms. An analysis of the SARs for MAO inhibition by 3‐chloro‐1H‐indole‐5,6‐dicarbonitriles showed that methylation of the indole nitrogen eliminates MAO-B inhibition activity, and replacement of the 2-phenyl ring with the thienyl results in a 9-fold reduction of MAO-B inhibition activity. A series of 3‐bromo‐1-hydroxy‐1H‐indole‐5,6‐dicarbonitriles are, in turn, comparatively weaker MAO inhibitors. It may be concluded that indole-5,6-dicarbonitrile derivatives are suitable leads for the design MAO inhibitors for the treatment of disorders such as Parkinson’s disease and depressionen_US
dc.description.sponsorshipMedical Research Council and National Research Foundation of South Africa (Grant specific unique reference numbers (UID) 85642 and 80647)en_US
dc.subjectMonoamine oxidaseen_US
dc.titleInhibition of monoamine oxidase by indole-5,6-dicarbonitrile derivativesen_US
dc.contributor.researchID12264954 - Petzer, Anél
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus

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