dc.contributor.author | Legoabe, Lesetja J. | |
dc.contributor.author | Petzer, Anél | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.date.accessioned | 2016-08-19T08:09:08Z | |
dc.date.available | 2016-08-19T08:09:08Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Legoabe, L.J. et al. 2015. The synthesis and evaluation of C7-substituted α-tetralone derivatives as inhibitors of monoamine oxidase. Chemical biology & drug design, 86(4):895-904. [https://doi.org/10.1111/cbdd.12508] | en_US |
dc.identifier.issn | 1747-0277 | |
dc.identifier.issn | 1747-0285 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/18329 | |
dc.identifier.uri | https://onlinelibrary.wiley.com/doi/abs/10.1111/cbdd.12508 | |
dc.identifier.uri | https://doi.org/10.1111/cbdd.12508 | |
dc.description.abstract | Based on a previous report that α-tetralone (3,4-dihydro-2H-naphthalen-1-one) is a promising scaffold for the design of highly potent inhibitors of the enzyme, monoamine oxidase, the present study investigates the monoamine oxidase inhibitory properties of a synthetic series of fifteen C7-substituted α-tetralone derivatives. Arylalkyloxy substitution on C7 of the α-tetralone moiety yielded compounds with high inhibition potencies toward the human monoamine oxidase-B isoform with all compounds possessing IC50 values in the submicromolar range (0.00089–0.047 μm). The C7-substituted α-tetralones also were highly potent monoamine oxidase-A inhibitors with thirteen (of fifteen) compounds possessing IC50 values in the submicromolar range (0.010–0.741 μm). The α-tetralones were, however, in each instance selective for monoamine oxidase-B over the monoamine oxidase-A isoform. Dialyses of enzyme–inhibitor mixtures show that, while a representative inhibitor acts as a reversible monoamine oxidase-A inhibitor, inhibition of monoamine oxidase-B is not readily reversed by dialysis. Using a molecular modeling approach, possible binding orientations and interactions of selected α-tetralones with the active sites of the monoamine oxidases are also proposed. This study suggests that C7-substituted α-tetralones are promising monoamine oxidase inhibitors and may represent lead compounds for the development of therapies for 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,
80647 and 80637] | en_US |
dc.language.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.subject | Competitive | en_US |
dc.subject | Dialysis | en_US |
dc.subject | Inhibition | en_US |
dc.subject | Monoamine oxidase | en_US |
dc.subject | Reversible | en_US |
dc.subject | α-Tetralone | en_US |
dc.title | The synthesis and evaluation of C7-substituted α-tetralone derivatives as inhibitors of monoamine oxidase | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 12902608 - Legoabe, Lesetja Jan | |
dc.contributor.researchID | 12264954 - Petzer, Anél | |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |