Title:Synthesis and Evaluation of 2-benzylidene-1-tetralone Derivatives for Monoamine Oxidase Inhibitory Activity
VOLUME: 18 ISSUE: 2
Author(s):Klaudia T. Amakali, Lesetja J. Legoabe*, Anel Petzer and Jacobus P. Petzer
Affiliation:Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520
Keywords:2-benzylidene-1-tetralone, chalcone, monoamine oxidase, tetralone, inhibitor, parkinson's disease.
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.
