Neuroprotective or neurotoxic activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline and related compounds

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) 1 and various 5- or 6,7-substituted analogues were synthesized and assayed for neurotoxicity towards SH-SY5Y cells. Among mono-substituted derivatives of 1, hydroxyl substitution decreased the toxicity, while methoxyl substitution increased it. Disubstituted derivatives of 1, 5a and 5b, showed the opposite tendency. Hydroxy-1MeTIQ derivatives were tested for neuroprotective activity, and 3b and 4b exhibited greater efficacy than 1. We suggest that hydroxy-1MeTIQ derivatives, especially 4b, may have potential for the treatment of Parkinson's disease.