dc.contributor.author | Chirkova, Zhanna V. | |
dc.contributor.author | Petzer, Anél | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.contributor.author | Kabanova, Mariya V. | |
dc.contributor.author | Filimonov, Sergey I. | |
dc.date.accessioned | 2016-08-18T12:19:54Z | |
dc.date.available | 2016-08-18T12:19:54Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Chirkova, Z.V. et al. 2015. Inhibition of monoamine oxidase by indole-5,6-dicarbonitrile derivatives. Bioorganic & medicinal chemistry letters, 25(6):1206-1211. [https://doi.org/10.1016/j.bmcl.2015.01.061] | en_US |
dc.identifier.issn | 0960-894X | |
dc.identifier.issn | 1464-3405 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/18318 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0960894X15000827 | |
dc.identifier.uri | https://doi.org/10.1016/j.bmcl.2015.01.061 | |
dc.description.abstract | Recent 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 depression | en_US |
dc.description.sponsorship | Medical Research Council and National Research Foundation of
South Africa (Grant specific unique reference numbers (UID)
85642 and 80647) | en_US |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.subject | MAO | en_US |
dc.subject | Monoamine oxidase | en_US |
dc.subject | Inhibition | en_US |
dc.subject | Indole‐5,6‐dicarbonitrile | en_US |
dc.subject | Phthalonitrile | en_US |
dc.subject | Reversible | en_US |
dc.title | Inhibition of monoamine oxidase by indole-5,6-dicarbonitrile derivatives | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 12264954 - Petzer, Anél | |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |