title: Studies on the monoamine oxidase-B-catalyzed biotransformation of 4-azaaryl-1-methyl-1,2,3,6-tetrahydropyridine derivatives.
abstract: The substrate properties of a series of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridinyl (MPTP) analogues in which the C-4 phenyl group has been replaced with various 4-azaaryl moieties have been examined in an effort to evaluate the contribution of electronic, polar, and steric parameters to the MAO-B-catalyzed oxidation of this type of cyclic tertiary allylamine to the corresponding dihydropyridinium metabolite. No significant correlation could be found with the calculated energy of the C-H bond undergoing cleavage. A general trend, however, was observed between the magnitude of the log P value with the magnitude of kcat/Km. The results indicate that the placement of a polar nitrogen atom in the space occupied by the phenyl group of MPTP leads to a dramatic decrease in substrate properties. Enhanced substrate properties, however, were observed when benzoazaarenes replaced the corresponding five-membered azaarenes. These results are consistent with our previously published molecular model of the active site of MAO-B.
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Nimkar
authors.forename: S
authors.initials: S
authors.lastname: Mabic
authors.forename: A H
authors.initials: AH
authors.lastname: Anderson
authors.forename: S L
authors.initials: SL
authors.lastname: Palmer
authors.forename: T H
authors.initials: TH
authors.lastname: Graham
authors.forename: M
authors.initials: M
authors.lastname: de Jonge
authors.forename: L
authors.initials: L
authors.lastname: Hazelwood
authors.forename: S J
authors.initials: SJ
authors.lastname: Hislop
authors.forename: N
authors.initials: N
authors.lastname: Castagnoli
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000737:chemistry*; D002384:Catalysis; D002417:Cattle; D007700:Kinetics; D008099:Liver / Q000737:chemistry; D008995:Monoamine Oxidase / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D001372:Aza Compounds; D011725:Pyridines; D008995:Monoamine Oxidase