Studies on the monoamine oxidase-B-catalyzed biotransformation of 4-azaaryl-1-methyl-1,2,3,6-tetrahydropyridine derivatives.
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.
Nimkar
S K
SK
Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA.
Mabic
S
S
Anderson
A H
AH
Palmer
S L
SL
Graham
T H
TH
de Jonge
M
M
Hazelwood
L
L
Hislop
S J
SJ
Castagnoli
N
N
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
D001372:Aza Compounds; D011725:Pyridines; D008995:Monoamine Oxidase