title: The inhibition of monoamine oxidase by 8-(2-phenoxyethoxy)caffeine analogues.
abstract: Previous studies have documented that substituted 8-oxycaffeines act as inhibitors of human monoamine oxidase (MAO) B. A particularly potent inhibitor among the reported compounds was 8-(2-phenoxyethoxy)caffeine with an IC50 value of 0.383 µM towards MAO-B. In an attempt to improve on the inhibition potency of this compound and to discover highly potent reversible MAO-B inhibitors, in the present study, a series of 8-(2-phenoxyethoxy)caffeine analogues containing various substituents on C4 of the phenoxy ring, were synthesized and evaluated as inhibitors of human MAO-A and -B. The results show that the 8-(2-phenoxyethoxy)caffeine analogues are selective and reversible MAO-B inhibitors with the most potent homologue, 8-{2-[4-(trifluoromethyl)phenoxy]ethoxy}caffeine, exhibiting an IC50 value of 0.061 μM. These highly potent inhibitors are useful leads in the design of therapies for neurodegenerative disorders such as Parkinson's disease.
authors.affiliation: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Strydom
authors.forename: J J
authors.initials: JJ
authors.lastname: Bergh
authors.forename: J P
authors.initials: JP
authors.lastname: Petzer
mesh_terms: D002110:Caffeine / Q000031:analogs & derivatives*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008996:Monoamine Oxidase Inhibitors; D002110:Caffeine