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

Eur J Med Chem. 2006 Feb;41(2):241-52. doi: 10.1016/j.ejmech.2005.11.003. Epub 2006 Jan 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Brain / pathology*
  • Cells, Cultured
  • Membrane Transport Proteins / metabolism
  • Microscopy, Fluorescence, Multiphoton
  • Neurotoxins / metabolism*
  • PC12 Cells / pathology
  • Parkinson Disease / drug therapy
  • Parkinson Disease / pathology*
  • Rats
  • Tetrahydroisoquinolines / chemical synthesis*
  • Tetrahydroisoquinolines / pharmacology*

Substances

  • Membrane Transport Proteins
  • Neurotoxins
  • Tetrahydroisoquinolines
  • 1,2,3,4-tetrahydro-1-phenylisoquinoline