Amakali, Klaudia T.Legoabe, Lesetja J.Petzer, AnélPetzer, Jacobus P.2018-08-212018-08-212018Amakali, 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]1871-52491875-6166 (Online)http://hdl.handle.net/10394/30747http://www.eurekaselect.com/161739https://doi.org/10.2174/1871524918666180501121638Background: 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 diseaseen2-Benzylidene-1-tetraloneChalconeMonoamine oxidaseTetraloneInhibitorParkinson's diseaseArticle