Cognitive-enhancing activity of decursin derivatives

Decursin 유도체의 인지기능 개선 활성

  • Published : 2008.06.30

Abstract

Two decursin derivatives were synthesized from decursinol. Compounds 1 and 2 were determined as 7-{3-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-propoxy}-8,8-dimethyl-7,8-dihydro-6H-pyranochromen-2-one (1) and decursinol 3'-O-E-pmethoxycinnamic acid ester (2), respectively and newly reported. Compounds 1 and 2 significantly inhibited AChE activity and ameliorated memory impairment induced in mice by scopolamine (1.0 mg/kg body weight s.c.) as measured in passive avoidance test. We suggest, therefore, that compounds 1 and 2 has both anti-AChE and anti-amnesic activities that may ultimately hold significant therapeutic value in alleviating certain memory impairment observed in Alzheimer's disease.

Keywords

References

  1. Deutsch, J.A. (1971) The cholinergic synapse and the site of memory. Science 174: 788-794 https://doi.org/10.1126/science.174.4011.788
  2. Iqbal, K., Winblad, B., Nishimura, T., Takeda, M. and Wisniewski, H.M., eds. (1997) Alzheimer's disease: biology, diagnosis and therapeutics. Chichester, England: Wiley
  3. Davies, P. and Maloney, A.F. (1976) Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2: 1403-1410
  4. Whitehouse, P.J., Price, D.L., Clark, A.W., Coyle, J.T. and DeLong, M.R. (1981) Alzheimer disease: evidence of selective loss of cholinergic neurons in the nucleus basalis. Ann. Neurol. 10: 122-126 https://doi.org/10.1002/ana.410100203
  5. Bartus, R.T., Dean, R.L., Beer, B. and Lippa, A.S. (1982) The cholinergic hyphothesis of geriatic memory dysfuntion. Science 217: 408-414 https://doi.org/10.1126/science.7046051
  6. Coyle, J.T., Price, D.L., DeLong, M.R. (1983) Alzheimer's disease: a disorder of cortical cholinergic innervation. Science 219: 1184-1190 https://doi.org/10.1126/science.6338589
  7. Lang, W. and Henke, H. (1983) Cholinergic receptor binding and auto- radiography in brains of non-neurological and senile dementia of Alzheimer-type patients. Brain Res. 267: 271-280 https://doi.org/10.1016/0006-8993(83)90879-X
  8. Christensen, H., Maltby, N., Jorm, A.F., Creasey, H. and Broe, G.A. (1992) Cholinergic 'Blockade' as a model of the cognitive deficits in Alzheimer' disease. Brain 115: 1681-1699 https://doi.org/10.1093/brain/115.6.1681
  9. Kang, S.Y., Lee, K.Y., Sung, S.H., Park, M.J. and Kim, Y.C. (2001) Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. J. Nat.Prod. 64: 683-6 https://doi.org/10.1021/np000441w
  10. Kang, S.Y., Lee, K.Y., Park, M.J., Kim, Y.C., Markelonis, G.J., Oh ,T.H. and Kim Y.C. (2003) Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice. Neurobiol. Learn. Mem. 79: 11-18 https://doi.org/10.1016/S1074-7427(02)00007-2
  11. Knauber J. and Müller, W.E. (2003) Anseculin improves passive avoidance learning of aged mice. Pharmacol. Res. 47: 225-233 https://doi.org/10.1016/S1043-6618(02)00311-0
  12. Hilgert, M., Nöldner, M., Chatterjee, S.S. and Klein, J. (1999) KA-672 inhibits rat brain acetylcholinesterase in vitro but not in vivo. Neurosci. Lett. 263: 193-196 https://doi.org/10.1016/S0304-3940(99)00149-4
  13. Reisner, E., Noldner, M., $Ro{ss}ner$ S, Chatterjee, S.S., Bigl, V. and Schliebs, R. (1999) Acute effect of KA-672, a putative cognitive enhancer, on neurotransmitter receptor binding in mouse brain. Neurosci. Lett. 274: 187-190 https://doi.org/10.1016/S0304-3940(99)00725-9
  14. Teismann, P. and Ferger, B. (2000) In vivo effects of the putative cognitive enhancer KA-672.HCl in comparison with 8-hydroxy-2-(DI-N-propylamino) tetralin and haloperidol on dopamine, 3,4-dihydroxypheny-lacetic acid, serotonin and 5-ydroxyindoleacetic acid levels in striatal and cortical brain regions. Prog. Neuro-Psychoph. 24: 337-348 https://doi.org/10.1016/S0278-5846(99)00088-3
  15. Kim, S.R., Kang, S.Y., Lee, K.Y., Kim, S.H., Markelonis, G..J., Oh, T.H. and Kim, Y.C. (2003) Anti-amnestic activity of E-p-methoxycinnamic acid from Scrophularia buergeriana. Cogn. Brain Res. 17: 454-461 https://doi.org/10.1016/S0926-6410(03)00161-7
  16. Ellman, G.L., Courtney, K.D., Andres, V. and Featherstone, R.M. (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7: 68-75
  17. Hoerr, R. and Noeldner, M. (2002) Ensaculin (KA-672 . HCl): A Multitransmitter Approach to Dementia Treatment. CNS Drug Reviews 8: 143-158 https://doi.org/10.1111/j.1527-3458.2002.tb00220.x
  18. Madgula, V.L., Avula, B., Reddy, V.L.N., Khan, I.A. and Khan, S.I. (2007) Transport of decursin and decursinol angelate across Caco-2 and MDR-MDCK cell monolayers: in vitro models for intestinal and blood-brain barrier permeability. Planta Med. 73:330-335 https://doi.org/10.1055/s-2007-967137
  19. Kim, D.H., Kim, D.Y., Kim, Y.C., Jung, J.W., Lee, S., Yoon, B.H., Cheong, J.H., Kim, Y.S., Kang, S.S., Ko, K.H., Ryu, J.H. (2007) Nodakenin, a coumarin compound, ameliorates scopolamine-induced memory disruption in mice. Life Sci. 80: 1944-1950 https://doi.org/10.1016/j.lfs.2007.02.023