Synthesis and Evaluation of 2-benzylidene-1-tetralone Derivatives for Monoamine Oxidase Inhibitory Activity

Author(s): Klaudia T. Amakali, Lesetja J. Legoabe*, Anel Petzer, Jacobus P. Petzer

Journal Name: Central Nervous System Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

Volume 18 , Issue 2 , 2018

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Graphical 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.

Keywords: 2-benzylidene-1-tetralone, chalcone, monoamine oxidase, tetralone, inhibitor, parkinson's disease.

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Article Details

Year: 2018
Published on: 18 July, 2018
Page: [136 - 149]
Pages: 14
DOI: 10.2174/1871524918666180501121638
Price: $65

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