Structural analogs of huperzine A improve survival in guinea pigs exposed to soman

Hendra Gunosewoyo, Suresh K. Tipparaju, Marco Pieroni, Ying Wang, Bhupendra P. Doctor, Madhusoodana P. Nambiar, Alan P. Kozikowski

Research output: Contribution to journalArticlepeer-review


Chemical warfare nerve agents such as soman exert their toxic effects through an irreversible inhibition of acetylcholinesterase (AChE) and subsequently glutamatergic function, leading to uncontrolled seizures. The natural alkaloid (-)-huperzine A is a potent inhibitor of AChE and has been demonstrated to exert neuroprotection at an appropriate dose. It is hypothesized that analogs of both (+)- and (-)-huperzine A with an improved ability to interact with NMDA receptors together with reduced AChE inhibition will exhibit more effective neuroprotection against nerve agents. In this manuscript, the tested huperzine A analogs 2 and 3 were demonstrated to improve survival of guinea pigs exposed to soman at either 1.2 or 2 × LD50.

Original languageEnglish (US)
Pages (from-to)1544-1547
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number5
StatePublished - Mar 1 2013


  • Acetylcholinesterase
  • Huperzine A analogs
  • Nerve agent
  • Neuroprotection
  • Soman

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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