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306068.0 [No comment] 10.06.2008 15:19 Released

ID: 306068.0, MPI für Festkörperforschung / FKF Publikationen 2006
Toxicity and metabolism of the chloral-derived mammalian alkaloid 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in PC12 cells
Authors:Bringmann, G.; Feineis, D.; Münchbach, M.; God, R.; Peters, K.; Peters, E. M.; Mössner, R.; Lesch, K. P.
Date of Publication (YYYY-MM-DD):2006
Title of Journal:Zeitschrift für Naturforschung C
Issue / Number:7-8
Start Page:601
End Page:610
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Chloral-derived beta-carbolines, which are structurally similar to the
dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP, 5), are discussed to contribute to neuronal cell death in
idiopathic Parkinson's disease. The cytotoxicity of
1-trichloromethyl-1,2,3,4-tetrahydro-p-carboline (TaClo, 4) to
neuronal-like clonal pheochromocytoma PC12 cells was examined by the
determination of lactate dehydrogenase (LDH) release. After incubation
for 48 h, 4 showed a strong dose-dependent cytotoxic activity towards
PC12 cells with an ED50 value of 230 mu M. In PC12 cells reductive
dehalogenation of 4 was observed giving rise to the formation of
1-dichloromethyl-1,2,3,4-tetrahydro-beta-carboline (6) as a main TaClo
metabolite exhibiting a cytotoxic potential comparable to that of
TaClo. An X-ray structure analysis, performed for the trifluoroacetyl
derivative of 6, revealed the N-substituent of such a highly
chlorinated agent to be dramatically pushed out of the beta-carboline
ring 'plane' due to the high steric demand of the huge dichloromethyl
group at C(1).
Free Keywords:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo); rat
phaeochromocytoma (PC12) cells; cytotoxicity; Parkinson's disease
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für Festkörperforschung
External Affiliations:Univ Wurzburg, Inst Organ Chem, D-97074 Wurzburg, Germany.
; Max Planck Inst Festkorperforsch, D-70506 Stuttgart, Germany.
; Univ Wurzburg, Klin & Poliklin Psychiat & Psychotherapie, D-97080 Wurzburg, Germany.
Identifiers:ISI:000240219700022 [ID No:1]
ISSN:0939-5075 [ID No:2]