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|
|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|
|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]
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