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

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Gunosewoyo H, Tipparaju SK, Pieroni M, Wang Y, Doctor BP, Nambiar MP, Kozikowski AP

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

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1544-7. doi: 10.1016/j.bmcl.2012.11.083. Epub 2012 Dec 1.

PubMed ID

23395652 [ View in PubMed

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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 2xLD(50).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Huperzine A	Acetylcholinesterase	IC 50 (nM)	45	N/A	N/A	Details