3-Coumaranone derivatives as inhibitors of monoamine oxidase.
The present study examines the monoamine oxidase (MAO) inhibitory properties of a series of 20 3-coumaranone [benzofuran-3(2H)-one] derivatives. The 3-coumaranone derivatives are structurally related to series of α-tetralone and 1-indanone derivatives, which have recently been shown to potently inhibit MAO, with selectivity for MAO-B (in preference to the MAO-A isoform). 3-Coumaranones are similarly found to selectively inhibit human MAO-B with half-maximal inhibitory concentration (IC50) values of 0.004-1.05 µM. Nine compounds exhibited IC50<0.05 µM for the inhibition of MAO-B. For the inhibition of human MAO-A, IC50 values ranged from 0.586 to >100 µM, with only one compound possessing an IC50<1 µM. For selected 3-coumaranone derivatives, it is established that MAO-A and MAO-B inhibition are reversible since dialysis of enzyme-inhibitor mixtures almost completely restores enzyme activity. On the basis of the selectivity profiles and potent action, it may be concluded that the 3-coumaranone derivatives are suitable leads for the development of selective MAO-B inhibitors as potential treatment for disorders such as Parkinson's disease and Alzheimer's disease.
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa ; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa.
Adriaan S
AS
Van Dyk
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa ; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa.
Jacobus P
JP
Petzer
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
Anél
A
Petzer
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
Lesetja J
LJ
Legoabe
D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes; D008954:Models, Biological; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
C585771:3-coumaranone; D003374:Coumarins; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011994:Recombinant Proteins; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human
MAO; Parkinson’s disease; benzofuran-3(2H)-one; competitive; inhibition; reversible