2-Heteroarylidene-1-indanone derivatives as inhibitors of monoamine oxidase.
In the present study a series of fifteen 2-heteroarylidene-1-indanone derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. These compounds are structurally related to series of heterocyclic chalcone derivatives which have previously been shown to act as MAO-B specific inhibitors. The results document that the 2-heteroarylidene-1-indanones are in vitro inhibitors of MAO-B, displaying IC50values of 0.0044-1.53μM. Although with lower potencies, the derivatives also inhibit the MAO-A isoform with IC50values as low as 0.061μM. An analysis of the structure-activity relationships for MAO-B inhibition indicates that substitution with the methoxy group on the A-ring leads to a significant enhancement in MAO-B inhibition compared to the unsubstituted homologues while the effect of the heteroaromatic substituent on activity, in decreasing order is: 5-bromo-2-furan>5-methyl-2-furan>2-pyridine≈2-thiophene>cyclohexyl>3-pyridine≈2-furan. It may therefore be concluded that 2-heteroarylidene-1-indanone derivatives are promising leads for the design of MAO inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders.
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.
Magdalena S
MS
Nel
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.
Anél
A
Petzer
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.
Jacobus P
JP
Petzer
Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: lesetja.legoabe@nwu.ac.za.
Lesetja J
LJ
Legoabe
D004305:Dose-Response Relationship, Drug; D006801:Humans; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C013352:indacrinone; D008995:Monoamine Oxidase
Chalcone; Heterocyclic; Indanone; Inhibition; MAO; Monoamine oxidase; SAR