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

Abstract

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
Volume23
Issue number5
DOIs
StatePublished - Mar 1 2013

Keywords

  • 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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