Synthesis and in vitro cytotoxicity of 1,2,3,4-tetrahydroisoquinoline derivatives.
Several 1-alkyl-1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives, which may play a role in Parkinson's disease, have been synthesized via Pummerer-type cyclization of the sulfonium ion formed in situ from N-formyl sulfoxide. Using an in vitro trypan blue exclusion assay, high concentrations of TIQ derivatives possessing bulky alkyl group substituents such as 1-cyclobutyl-, 1-cyclohexyl-, 1-phenyl- or 1-benzyl- at the C-1 position were found to significantly affect the viability of PC12 cells. Moreover, TIQ derivatives that moderately or strongly induced apoptosis (e.g., 1-phenyl-TIQ and 1-cyclohexyl-TIQ, respectively) paralleled the results obtained using the trypan blue exclusion assay. These results suggest that the size and electron-donating properties of functional groups may affect the cytotoxicity of TIQ derivatives.
Saitoh
Toshiaki
T
Department of Organic Reaction Chemistry, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-0042, Japan.
Abe
Kenji
K
Ishikawa
Masami
M
Nakatani
Masanao
M
Shimazu
Seiichiro
S
Satoh
Noriyuki
N
Yoneda
Fumio
F
Taguchi
Kyoji
K
Horiguchi
Yoshie
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D026901:Membrane Transport Proteins / Q000378:metabolism; D036641:Microscopy, Fluorescence, Multiphoton; D009498:Neurotoxins / Q000378:metabolism*; D016716:PC12 Cells / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
D026901:Membrane Transport Proteins; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines; C096775:1,2,3,4-tetrahydro-1-phenylisoquinoline