Facile synthesis and in vitro properties of 1-alkyl- and 1-alkyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline derivatives on PC12 cells
2009
Abstract The synthesis of several 1-alkyl-1,2,3,4-tetrahydroisoquinolines, which may play an important role in Parkinson's disease, has been achieved by modified Pictet–Spengler cyclization of the formyliminium ion. The direct cytotoxicity and preventative effects towards MPP + -mediated death of PC12 cells were estimated. The cytotoxicities of 1-alkyl-TIQs were apoptotic and depended on their lipophilic properties. Conversely, introducing the N -propargyl substituent reduced cytotoxicity. 1-Methyl-, 1-methyl- N -propargyl- and 1-cyclopropyl-TIQ partially inhibited MPP + -induced cell death, whereas relatively large alkyl substituents at the first position did not enhance the viability of PC12 cells. In summary, our findings suggest a crucial role for the N -propargyl functional group for the effective reduction of cytotoxicity, and show the importance of size and lipophilicity of substituents at the 1-position of 1-alkyl-TIQs.
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