Toxicity and metabolism of the chloral-derived mammalian alkaloid 
1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in PC12 cells

Bringmann, G.; Feineis, D.; Münchbach, M.; God, R.; Peters, K.; Peters, E. M.; Mössner, R.; Lesch, K. P.

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Toxicity and metabolism of the chloral-derived mammalian alkaloid 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in PC12 cells

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Peters, K.
Former Scientific Facilities, Max Planck Institute for Solid State Research, Max Planck Society;

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Peters, E. M.
Former Scientific Facilities, Max Planck Institute for Solid State Research, Max Planck Society;

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Citation

Bringmann, G., Feineis, D., Münchbach, M., God, R., Peters, K., Peters, E. M., et al. (2006). Toxicity and metabolism of the chloral-derived mammalian alkaloid 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in PC12 cells. Zeitschrift für Naturforschung C, 61(7-8), 601-610.

Cite as: https://hdl.handle.net/21.11116/0000-000F-0013-B

Abstract

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).