Synthesis, chiral chromatographic separation, and biological activities of the enantiomers of 10,10-dimethylhuperzine A

Bioorg Med Chem Lett. 2000 Nov 6;10(21):2467-9. doi: 10.1016/s0960-894x(00)00494-7.

Abstract

(+/-)-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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Alkaloids
  • Animals
  • Cell Survival
  • Cells, Cultured
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology
  • Chromatography, High Pressure Liquid
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology
  • Glutamic Acid / toxicity
  • Humans
  • Kinetics
  • Molecular Structure
  • Neurons / cytology
  • Neurons / drug effects
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology
  • Prosencephalon / cytology
  • Prosencephalon / embryology
  • Rats
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / pharmacology*
  • Stereoisomerism

Substances

  • 10,10-dimethylhuperzine A
  • Alkaloids
  • Cholinesterase Inhibitors
  • Drugs, Chinese Herbal
  • Neuroprotective Agents
  • Sesquiterpenes
  • huperzine A
  • Glutamic Acid
  • Acetylcholine