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 journalArticle

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
Externally publishedYes

Fingerprint

Soman
Guinea Pigs
Acetylcholinesterase
Chemical Warfare Agents
Chemical warfare
Poisons
Lethal Dose 50
Cholinesterase Inhibitors
N-Methyl-D-Aspartate Receptors
Alkaloids
Seizures
huperzine A
Neuroprotection
Nerve Agents

Keywords

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

ASJC Scopus subject areas

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

Cite this

Gunosewoyo, H., Tipparaju, S. K., Pieroni, M., Wang, Y., Doctor, B. P., Nambiar, M. P., & Kozikowski, A. P. (2013). Structural analogs of huperzine A improve survival in guinea pigs exposed to soman. Bioorganic and Medicinal Chemistry Letters, 23(5), 1544-1547. https://doi.org/10.1016/j.bmcl.2012.11.083

Structural analogs of huperzine A improve survival in guinea pigs exposed to soman. / Gunosewoyo, Hendra; Tipparaju, Suresh K.; Pieroni, Marco; Wang, Ying; Doctor, Bhupendra P.; Nambiar, Madhusoodana P.; Kozikowski, Alan P.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 5, 01.03.2013, p. 1544-1547.

Research output: Contribution to journalArticle

Gunosewoyo, H, Tipparaju, SK, Pieroni, M, Wang, Y, Doctor, BP, Nambiar, MP & Kozikowski, AP 2013, 'Structural analogs of huperzine A improve survival in guinea pigs exposed to soman', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 5, pp. 1544-1547. https://doi.org/10.1016/j.bmcl.2012.11.083
Gunosewoyo, Hendra ; Tipparaju, Suresh K. ; Pieroni, Marco ; Wang, Ying ; Doctor, Bhupendra P. ; Nambiar, Madhusoodana P. ; Kozikowski, Alan P. / Structural analogs of huperzine A improve survival in guinea pigs exposed to soman. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 5. pp. 1544-1547.
@article{4243b62e81304e3f901a3751bbd09270,
title = "Structural analogs of huperzine A improve survival in guinea pigs exposed to soman",
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.",
keywords = "Acetylcholinesterase, Huperzine A analogs, Nerve agent, Neuroprotection, Soman",
author = "Hendra Gunosewoyo and Tipparaju, {Suresh K.} and Marco Pieroni and Ying Wang and Doctor, {Bhupendra P.} and Nambiar, {Madhusoodana P.} and Kozikowski, {Alan P.}",
year = "2013",
month = "3",
day = "1",
doi = "10.1016/j.bmcl.2012.11.083",
language = "English (US)",
volume = "23",
pages = "1544--1547",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - Structural analogs of huperzine A improve survival in guinea pigs exposed to soman

AU - Gunosewoyo, Hendra

AU - Tipparaju, Suresh K.

AU - Pieroni, Marco

AU - Wang, Ying

AU - Doctor, Bhupendra P.

AU - Nambiar, Madhusoodana P.

AU - Kozikowski, Alan P.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

AB - 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.

KW - Acetylcholinesterase

KW - Huperzine A analogs

KW - Nerve agent

KW - Neuroprotection

KW - Soman

UR - http://www.scopus.com/inward/record.url?scp=84873703076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873703076&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2012.11.083

DO - 10.1016/j.bmcl.2012.11.083

M3 - Article

C2 - 23395652

AN - SCOPUS:84873703076

VL - 23

SP - 1544

EP - 1547

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 5

ER -