Synthesis and in vitro cytotoxicity of 1,2,3,4-tetrahydroisoquinoline derivatives

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• 作者：Toshiaki Saitoh ; Kenji Abe ; Masami Ishikawa ; Masanao Nakatani ; Seiichiro Shimazu ; Noriyuki Satoh ; Fumio Yoneda ; Kyoji Taguchi ; Yoshie Horiguchi
• 关键词：Pummerer-type cyclization ; 1 ; 2 ; 3 ; 4-Tetrahydroisoquinoline ; Structure– ; activity relationships ; Cytotoxicity ; Parkinson’ ; s disease
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：February 2006
• 年：2006
• 卷：41
• 期：2
• 页码：241-252
• 全文大小：506 K

文摘

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.