dc.contributor.author | Amakali, Klaudia T. | |
dc.contributor.author | Legoabe, Lesetja J. | |
dc.contributor.author | Petzer, Anél | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.date.accessioned | 2018-08-21T06:20:25Z | |
dc.date.available | 2018-08-21T06:20:25Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Amakali, K.T. et al. 2018. Synthesis and evaluation of 2-benzylidene-1-tetralone derivatives for monoamine oxidase inhibitory activity. Central nervous system agents in medicinal chemistry, 18(2):136-149. [https://doi.org/10.2174/1871524918666180501121638] | en_US |
dc.identifier.issn | 1871-5249 | |
dc.identifier.issn | 1875-6166 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/30747 | |
dc.identifier.uri | http://www.eurekaselect.com/161739 | |
dc.identifier.uri | https://doi.org/10.2174/1871524918666180501121638 | |
dc.description.abstract | Background: Chalcone has been identified as a promising lead for the design of Monoamine Oxidase (MAO) inhibitors. This study attempted to discover potent and selective chalcone-derived MAO inhibitors by synthesising a series consisting of various cyclic chalcone derivatives. The cyclic chalcones were selected based on the possibility that their restricted structures would confer a higher degree of MAO isoform selectivity, and included the following chemical classes: 1-indanone, 1- tetralone, 1-benzosuberone, chromone, thiochromone, 4-chromanone and 4-thiochromanone.
Methods: The cyclic chalcone derivatives were synthesised via a one-pot Claisen-Schmidt condensation reaction. The MAO inhibitory properties of the chalcone derivatives were evaluated with the recombinant human MAO-A and MAO-B enzymes and the potencies were expressed as the IC50 values. A selected inhibitor was docked into an active site model of MAO-B.
Results: The results showed that the cyclic chalcones are in general good potency, and in most instances specific inhibitors of the MAO-B isoform. Among these compounds, the 4-chromanone derivative was the most potent MAO-B inhibitor with an IC50 value of 0.156 µM. To further investigate the MAO inhibition of cyclic chalcones, a series of twenty-three 2-benzylidene-1-tetralone derivatives were synthesised and evaluated as MAO inhibitors. Most 2-benzylidene-1-tetralones possess good inhibitory activity and specificity for MAO-B with the most potent inhibitor displaying an IC50 value of 0.0064 µM, while the most potent MAO-A inhibitor possessed an IC50 value of 0.754 µM.
Conclusion: This study thus shows that certain cyclic chalcones are human MAO-B inhibitors, compounds that could be suitable for the treatment of neurodegenerative disorders such as Parkinson’s disease | en_US |
dc.language.iso | en | en_US |
dc.publisher | Bentham Science | en_US |
dc.subject | 2-Benzylidene-1-tetralone | en_US |
dc.subject | Chalcone | en_US |
dc.subject | Monoamine oxidase | en_US |
dc.subject | Tetralone | en_US |
dc.subject | Inhibitor | en_US |
dc.subject | Parkinson's disease | en_US |
dc.title | Synthesis and evaluation of 2-benzylidene-1-tetralone derivatives for monoamine oxidase inhibitory activity | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 12264954 - Petzer, Anél | |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |
dc.contributor.researchID | 12902608 - Legoabe, Lesetja Jan | |