In:
Zeitschrift für Naturforschung C, Walter de Gruyter GmbH, Vol. 61, No. 7-8 ( 2006-8-1), p. 601-610
Abstract:
Chloral-derived β-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-β-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 ED 50 value of 230 μᴍ. In PC12 cells reductive dehalogenation of 4 was observed giving rise to the formation of 1-dichloromethyl-1,2,3,4-tetrahydro-β-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 β-carboline ring ‘plane’ due to the high steric demand of the huge dichloromethyl group at C(1).
Type of Medium:
Online Resource
ISSN:
1865-7125
,
0939-5075
DOI:
10.1515/znc-2006-7-822
Language:
English
Publisher:
Walter de Gruyter GmbH
Publication Date:
2006
detail.hit.zdb_id:
2078107-6
SSG:
12
