title: Inhibition of human monoamine oxidase A and B by 5-phenoxy 8-aminoquinoline analogs.
abstract: 8-Aminoquinolines (8-AQs) are important class of anti-infective therapeutics. 5-Phenoxy 8-aminoquinoline analogs have shown improved metabolic stability compared to primaquine. In view or predictive role of monoamine oxidases (MAO) in metabolism of 8-aminoquinolines the 5-phenoxy analogs were evaluated in vitro for the inhibition of recombinant human MAO-A and MAO-B. The analogs were several folds more potent inhibitors of MAO-A and MAO-B compared to primaquine, the parent drug, with selectivity for MAO-B. 5-(4-Trifluoromethylphenoxy)-4-methylprimaquine (6) Inhibited MAO-B with IC(50) value of 150 nM (626-fold more potent than primaquine). These results will have important implications in optimizing metabolic stability of 8-AQs to improve therapeutic value and also indicate scope for development of 8-AQs as selective MAO inhibitors.
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, MS 38677, USA.
authors.forename: Narayan D
authors.initials: ND
authors.lastname: Chaurasiya
authors.forename: Shobana
authors.initials: S
authors.lastname: Ganesan
authors.forename: N P Dhammika
authors.initials: NP
authors.lastname: Nanayakkara
authors.forename: Luiza R S
authors.initials: LR
authors.lastname: Dias
authors.forename: Larry A
authors.initials: LA
authors.lastname: Walker
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011319:Primaquine / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D008996:Monoamine Oxidase Inhibitors; D010636:Phenols; D008995:Monoamine Oxidase; D011319:Primaquine; C080436:8-aminoquinoline