2-Benzylidene-1-indanone derivatives as inhibitors of monoamine oxidase

In the present study, a series of twenty-two 2-benzylidene-1-indanone derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The 2-benzylidene-1-indanone derivatives are structurally related to a series of benzylideneindanone derivatives which has previously been found to be MAO-B inhibitors. This study finds that the 2-benzylidene-1-indanones are MAO-B specific inhibitors with IC50 values <2.74 mu M. Among the compounds evaluated, twelve compounds exhibited IC50 <0.1 mu M and may be considered as high potency inhibitors. The 2-benzylidene-1-indanone derivatives also inhibited MAO-A with the most potent inhibition exhibited by 5g (IC50 = 0.131 mu M). An analysis of the structure-activity relationships for MAO-B inhibition show that substitution on the A-ring with a 5-hydroxy group and on the B-ring with halogens and the methyl group yield high potency inhibition. It may therefore be concluded that 2-benzylidene-1-indanone analogues are promising leads for design of therapies for disorders such as Parkinson's disease. (C) 2016 Elsevier Ltd. All rights reserved.