Synthesis and neuroprotective activity in cell culture of aminoadamantane analogues

Seven novel derivatives of aminoadamantane with 1-aminosubstituted group were synthesized from amantadine or memantine individually in order to find new neuroprotective agent. Six of them are amides of two precursors, one is a 1-amino derivative of memantine substituted with 2-hydroxy propyl. Their chemical structures were confirmed by ¹H NMR and HRMS. The neuroprotective activity in vitro was evaluated primarily with 500 μmol·L^-1 glutamate damaged SY5Y cell by measurement of MTT metabolic rate and LDH leakage rate. Glutamate reduced MTT metabolic rate, but increased LDH leakage rate significantly. The addition of new derivatives elevated the MTT value with their certain concentration, reduced cell death rate. Especially as for 3d and 4c, they fully normalized LDH leakage rate with concentration of 20 μmol·L^-1 during LDH measurement. These data indicated that 3d and 4c have significant protective effect on nerve cell against glutamate injury, deserved to be further tested and maybe helpful for treatment of neurodegenerative disease.