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Synthesis and in vitro Assay of New Triazole Linked Decursinol Derivatives Showing Inhibitory Activity against Cholinesterase for Alzheimer’s Disease Therapeutics

Park, Jung-Youl;Shin, Sujeong;Park, Kyoung Chan;Jeong, Eunju;Park, Jeong Ho

  • Received : 2016.01.06
  • Accepted : 2016.03.03
  • Published : 2016.04.20

Abstract

With the goal of developing Alzheimer’s disease therapeutics, we have designed and synthesized new triazole linked decursinol derivatives having potency inhibitory activities against cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)]. Since inhibition of cholinesterase (ChE) is still considered to be one of the most effective targets to treat AD patients, many new classes of ChE inhibitors have been synthesized. In an effort of identifying new type of cholinergic drug, decursinol derivatives 11-17 have been synthesized between decursinol and other biological interesting compounds such as lipoic acid, polyphenols, etc by using the click reaction and then evaluated their biological activities. Compound 12 (IC50 = 5.89 ± 0.31 mM against BuChE) showed more effective inhibitory activity against BuChE than galantamine (IC50 = 9.4 ± 2.5 mM). Decursinol derivatives can be considered a new class inhibitor for BuChE and can be applied to be a novel drug candidate to treat AD patients.

Keywords

Triazole linked decursinol derivatives;Alzheimer’s disease (AD);Acetylcholinesterase (AChE);Butyrylcholinesterase (BuChE)

References

  1. Winkler, J.; Thal, L. J.; Gage, F. H.; Fisher, L. J. J. Mol. Med. 1998, 76, 555. https://doi.org/10.1007/s001090050250
  2. Lleo, A.; Greenberg, S. M.; Growdon, J. H. Annu. Rev. Med. 2006, 57, 513. https://doi.org/10.1146/annurev.med.57.121304.131442
  3. Carreiras, M. C.; Marco, J. L. Curr. Pharm. Des. 2004, 10, 3167. https://doi.org/10.2174/1381612043383421
  4. Kwon, Y. E.; Park, J. Y.; No, K. T.; Shin, J. H.; Lee, S. K.; Eun, J. S.; Yang, J. H.; Shin, T. Y.; Kim, D. K.; Chae, B. S.; Leem, J. Y.; Kim, K. H. Bioorg. Med. Chem. 2007, 15, 6596. https://doi.org/10.1016/j.bmc.2007.07.003
  5. Jacobsen, J. S.; Reinhart, P.; Pangalos, M. N. Neuro. Rx.2005, 2, 612 https://doi.org/10.1602/neurorx.2.4.612
  6. Kurz, A. J. Neural. Transm. Suppl. 1998, 54, 295. https://doi.org/10.1007/978-3-7091-7508-8_29
  7. Sugimoto, H. Chem. Rec. 2001, 1, 63. https://doi.org/10.1002/1528-0691(2001)1:1<63::AID-TCR9>3.0.CO;2-J
  8. Jann, M. W. Pharmacotherapy 2000, 20, 1. https://doi.org/10.1592/phco.20.1.1.34664
  9. Zarotsky, V.; Sramek, J. J.; Cutler, N. R. Am. J. Health. Syst. Pharm. 2003, 60, 446.
  10. Perry, E. K.; Perry, R. H.; Blessed, G.; Tomlinson, B.E. Neuropathol. Appl. Neurobiol. 1978, 4, 273 https://doi.org/10.1111/j.1365-2990.1978.tb00545.x
  11. Darvesh, S.; Grantham, D. L.; Hopkins, D. A. J. Comp. Neurol. 1998, 393, 374. https://doi.org/10.1002/(SICI)1096-9861(19980413)393:3<374::AID-CNE8>3.0.CO;2-Z
  12. Kim, B. C.; Lee, S. H.; Jang, M.; Shon, M. Y.; Park, J. H. Bull. Korean Chem. Soc. 2013, 34, 3322. https://doi.org/10.5012/bkcs.2013.34.11.3322
  13. Greig, N. H.; Utsuki, T.; Ingram, D. K.; Wang, Y.; Pepeu, G.; Scali, C.; Yu, Q. S.; Mamczarz, J.; Hollway, H. W.; Giordano, T.; Chen, D.; Furukawa, K.; Sambamurti, K.; Brossi, A.; Lahiri, D. K. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 17213. https://doi.org/10.1073/pnas.0508575102
  14. Li, B.; Duysen, E.; Carlson, M.; Lockridge, O. J. Pharmacol.Exp. Ther. 2008, 324, 1146
  15. Yeun, G. H.; Lee, S. H.; Lim, Y. B.; Lee, H. S.; Won,M. H.; Lee, B. H.; Park, J. H. Bull. Korean Chem. Soc.2013, 34, 1025 https://doi.org/10.5012/bkcs.2013.34.4.1025
  16. Lee, S. H.; Kim, B. C.; Kim, J. K.; Lee, H. S.; Shon, M. Y.; Park, J. H. Bull. Korean Chem. Soc. 2014, 36, 1681.
  17. Woo, Y. J.; Lee, B. H.; Yeun, G. H.; Kim, H. J.; Won, M. H.; Kim, S. H.; Lee, B. H.; Park, J. H. Bull. Korean Chem. Soc. 2011, 32, 2593. https://doi.org/10.5012/bkcs.2011.32.8.2593
  18. Seo, Y. J.; Kwon, M. S.; Park, S. H.; Sim, Y. B.; Choi, S. M.; Huh, G. H.; Lee, J. K.; Suh, H. W. Arch. Pharm. Res. 2009, 32, 937. https://doi.org/10.1007/s12272-009-1617-z
  19. Yoon, M. Y.; Kim, Y. S.; Ryu, S. Y.; Choi, G. J.; Choi, Y. H.; Jang, K. S.; Cha, B. J.; Han, S. S.; Kim, J. C. Pestic. Biochem. Phys. 2011, 101, 118. https://doi.org/10.1016/j.pestbp.2011.08.013
  20. Jiang, C.; Guo, J.; Wang, Z.; Xiao, B.; Lee, H. J.; Lee, E. O.; Kim, S. H.; Lu, J. Breast Cancer Res. 2007, 9, 6.
  21. Ellman, G. I.; Coutney, K. D.; Jr. Andres, V.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88. https://doi.org/10.1016/0006-2952(61)90145-9
  22. Chouinard, G.; Jones, B. D. Am. J. Psychiatry. 1980,137, 16 https://doi.org/10.1176/ajp.137.1.16
  23. Baek, I. N.; Lee, B. Y.; Chae, J. W.; Song, G. Y.; Kang,W. K.; Kwon, K. I. Xenobiotica 2014, 44, 975 https://doi.org/10.3109/00498254.2014.924058
  24. Mori, H. Neuropathology 2000, 20, 55. https://doi.org/10.1046/j.1440-1789.2000.00317.x
  25. Park,H. Y.; Hwang, Y. H.; Yang, H. J.; Kim, H. K.; Song, K.S.; Ma, J. Y. J. Ethnopharmacol. 2014, 156, 182 https://doi.org/10.1016/j.jep.2014.09.004
  26. Lee, B.Y.; Weon, J. B.; Yun, B. R.; Lee, J. W.; Eom, M. R.; Ma,C. J. J. Chrom. Sci. 2014, 52, 482 https://doi.org/10.1093/chromsci/bmt064
  27. Kim, K. M.; Seo,J. L.; Kang, J. S. Mol. Cell. Toxi. 2014, 10, 83 https://doi.org/10.1007/s13273-014-0010-2
  28. Shi, L. S.;Kuo, S. C.; Sun, H. D.; Morris-Natschke, S. L.; Lee, K. H.;Wu, T. S. Bioorg. Med. Chem. 2014, 22, 1889. https://doi.org/10.1016/j.bmc.2014.01.052
  29. Abou El-Magd, R. M.; Park, H. K.; Kawazoe, T.; Iwana, S.; Ono, K.; Chung, S. P.; Miyano, M.; Yorita, K.; Sakai, T.; Fukui, K. J. Psycho. Pharmacol. 2010, 24, 1055 https://doi.org/10.1177/0269881109102644
  30. McPheeters, M. L.; Warren, Z.; Sathe, N. Pediatrics 2011, 127, 1312 https://doi.org/10.1542/peds.2011-0427
  31. Yildiz, A.; Vieta, E.; Leucht, S.; Baldessarini, R. J. Neuropsychopharmacol. 2011, 36, 375 https://doi.org/10.1038/npp.2010.192
  32. Gigante, A. D.; Lafer, B.; Yatham, L. N. CNS Drugs 2012, 26, 403 https://doi.org/10.2165/11631310-000000000-00000
  33. Leucht, S.; Cipriani, A.; Spineli, L. Lancet 2013, 382, 951 https://doi.org/10.1016/S0140-6736(13)60733-3
  34. Lafeuille, M. H.; Dean, J.; Carter, V. Curr. Med. Res. Opin. 2014, 30, 1643. https://doi.org/10.1185/03007995.2014.915211
  35. Woo, Y. J.; Lee, B. H.; Yeun, G. H.; Kim, H. J.; Ko, J. M.; Won, M. H.; Lee, B. H.; Park, J. H. Bull. Korean Chem. Soc. 2011, 32, 2997. https://doi.org/10.5012/bkcs.2011.32.8.2997
  36. Primo-Parmo, S.; Bartels, C.; Wiersema, B.; van der Apek, A.; Innis, J.; Du, B. L. Am. J. Hum. Genet. 1996, 58, 52.
  37. Rosini, M.; Andrisano, V.; Bartolini, M.; Bolognesi, M. L.; Hrelia, P.; Minarini, A.; Tarozzi, A.; Melchiorre, C. J. Med. Chem. 2005, 48, 360 https://doi.org/10.1021/jm049112h
  38. Ponpipom, M. M.; Bugianesi, R. L.; Blake, T. J. J. Med. Chem. 1987, 30, 705 https://doi.org/10.1021/jm00387a021
  39. Koufaki, M.; Detsi, A.; Theodorou, E.; Kiziridi, C.; Calogeropoulou, T.; Vassilopoulos, A.; Kourounakis, A. P.; Rekka, E.; Kourounakis, P. N.; Gaitanaki, C.; Papazafiri, P. Bioorg. Med. Chem. 2004, 12, 4835 https://doi.org/10.1016/j.bmc.2004.07.012
  40. Mesulam, M. M.; Geula, C. Ann. Neurol. 1994, 36, 722. https://doi.org/10.1002/ana.410360506