title: 2-Benzylidene-1-indanone derivatives as inhibitors of monoamine oxidase.
abstract: 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 <2.74μM. Among the compounds evaluated, twelve compounds exhibited IC50<0.1μM 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=0.131μM). 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.
authors: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors: Magdalena S
authors: MS
authors: Nel
authors: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors: Anél
authors: A
authors: Petzer
authors: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors: Jacobus P
authors: JP
authors: Petzer
authors: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: lesetja.legoabe@nwu.ac.za.
authors: Lesetja J
authors: LJ
authors: Legoabe
mesh_terms: D007189:Indans / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007189:Indans; D008996:Monoamine Oxidase Inhibitors
keywords: 2-Benzylidene-1-indanone; Inhibition; MAO; Monoamine oxidase; Reversible