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.

Graphical abstract1-Alkyl-1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives, have been synthesized using Pummerer-type cyclization of sulfoxides, possessing bulky alkyl group at the C-1 position found to significantly affect the viability of PC12 cells.Figure optionsDownload full-size imageDownload as PowerPoint slide