[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 micromol x 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 micromol x 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.
Li
Yan-ping
YP
Institute of Medicinal and Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
Li
Zhuo-rong
ZR
Cao
Jue
J
Tao
Yu-jie
YJ
D000547:Amantadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018698:Glutamic Acid / Q000633:toxicity; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008559:Memantine / Q000737:chemistry; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D000547:Amantadine; D007770:L-Lactate Dehydrogenase; D008559:Memantine