dc.contributor.author | Meiring, Letitia | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.contributor.author | Petzer, Anél | |
dc.date.accessioned | 2015-04-15T08:59:44Z | |
dc.date.available | 2015-04-15T08:59:44Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Meiring, L. et al. 2013. Inhibition of monoamine oxidase by 3,4-dihydro-2(1H)-quinolinone derivatives. Bioorganic & medicinal chemistry letters, 23(20):5498-5502. [https://doi.org/10.1016/j.bmcl.2013.08.071] | en_US |
dc.identifier.issn | 0960-894X | |
dc.identifier.issn | 1464-3405 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/13693 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0960894X13010111 | |
dc.identifier.uri | https://doi.org/10.1016/j.bmcl.2013.08.071 | |
dc.description.abstract | In the present study, a series of 3,4-dihydro-2(1H)-quinolinone derivatives were synthesized and evaluated
as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The 3,4-dihydro-2(1H)-
quinolinone derivatives are structurally related to a series of coumarin (1-benzopyran-2-one) derivatives
which have been reported to act as MAO-B inhibitors. The results document that the quinolinones are
highly potent and selective MAO-B inhibitors with most homologues exhibiting IC50 values in the nanomolar
range. The most potent MAO-B inhibitor, 7-(3-bromobenzyloxy)-3,4-dihydro-2(1H)-quinolinone,
exhibits an IC50 value of 2.9 nM with a 2750-fold selectivity for MAO-B over the MAO-A isoform. An analysis
of the structure–activity relationships for MAO-B inhibition shows that substitution on the C7 position
of the 3,4-dihydro-2(1H)-quinolinone scaffold leads to significantly more potent inhibition
compared to substitution on C6. In this regard, a benzyloxy substituent on C7 is more favourable than
phenylethoxy and phenylpropoxy substitution on this position. It may be concluded that C7-substituted
3,4-dihydro-2(1H)-quinolinones are promising leads for the therapy of Parkinson’s disease. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.subject | Monoamine oxidase | en_US |
dc.subject | Reversible inhibition | en_US |
dc.subject | Selectivity | en_US |
dc.subject | 3,4-Dihydro-2(1H)-quinolinone | en_US |
dc.subject | Structure-activity relationship | en_US |
dc.title | Inhibition of monoamine oxidase by 3,4-dihydro-2(1H)-quinolinone derivatives | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 21069565 - Meiring, Letitia | |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |
dc.contributor.researchID | 12264954 - Petzer, Anél | |