| Autor: |
Pretorius A; School of Pharmacy, North-West University, Potchefstroom 2520, South Africa., Ogunrombi MO, Fourie H, Terre'blanche G, Castagnoli N Jr, Bergh JJ, Petzer JP |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Jun 01; Vol. 18 (11), pp. 4111-8. Date of Electronic Publication: 2010 Apr 03. |
| DOI: |
10.1016/j.bmc.2010.03.079 |
| Abstrakt: |
The parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its corresponding five-membered ring analogue 1-methyl-3-phenyl-3-pyrroline are cyclic tertiary allylamines and good substrates of monoamine oxidase B (MAO-B). The MAO-B catalyzed 2-electron alpha-carbon oxidation of this class of substrates appears to be dependent on the presence of the allylic pi-bond since the corresponding saturated piperidinyl analogue of MPTP is reported not to be an MAO-B substrate. The only saturated cyclic tertiary amine known to act as an MAO-B substrate is the 3,4-cyclopropyl analogue of MPTP, 3-methyl-6-phenyl-3-azabicyclo[4.1.0]heptane. As part of our ongoing studies we have examined the MAO-B substrate properties of the corresponding pyrrolidinyl analogue, 1-methyl-3-phenylpyrrolidine, and the 3,4-cyclopropyl analogue, 3-methyl-1-phenyl-3-azabicyclo[3.1.0]hexane. The results document that both the pyrrolidinyl analogue [K(m)=234microM; V(max)=8.37nmol/(min-mg mitochondrial protein)] and the 3,4-cyclopropyl analogue [K(m)=148microM; V(max)=16.9nmol/(min-mg mitochondrial protein)] are substrates of baboon liver mitochondrial MAO-B. We also have compared the neurotoxic potential of these compounds in the C57BL/6 mouse. The results led us to conclude that these compounds are not MPTP-type neurotoxins. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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