title: Synthesis and in vitro cytotoxicity of 1,2,3,4-tetrahydroisoquinoline derivatives.
abstract: 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.
authors.affiliation: Department of Organic Reaction Chemistry, Showa Pharmaceutical University, 3-3165 Higashitamagawagakuen, Machida, Tokyo 194-0042, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saitoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.forename: Masami
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Masanao
authors.initials: M
authors.lastname: Nakatani
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Shimazu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Satoh
authors.forename: Fumio
authors.initials: F
authors.lastname: Yoneda
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Horiguchi
mesh_terms: 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*
chemical_list: D026901:Membrane Transport Proteins; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines; C096775:1,2,3,4-tetrahydro-1-phenylisoquinoline