Synthesis, chiral chromatographic separation, and biological activities of the enantiomers of 10,10-dimethylhuperzine A.
(+/-)-10,10-Dimethylhuperzine A (2, DMHA) has been synthesized, and its enantiomers have been separated using chiral HPLC. (-)-DMHA inhibits AChE with a Ki value approaching that of (-)-huperzine A, whereas (+)-DMHA shows no AChE inhibitory activity. On the other hand, both enantiomers are equally potent against glutamate-induced neurotoxicity when tested in neurons.
Rajendran
V
V
Department of Neurology, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
Prakash
K R
KR
Ved
H S
HS
Saxena
A
A
Doctor
B P
BP
Kozikowski
A P
AP
D000109:Acetylcholine / Q000378:metabolism; D000470:Alkaloids; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology; D051381:Rats; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism
C421343:10,10-dimethylhuperzine A; D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C050426:huperzine A; D018698:Glutamic Acid; D000109:Acetylcholine