Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Selective Butyrylcholinesterase Inhibitors Using Polyphenol-polyphenol Hybrid Molecules

  • Woo, Yeun-Ji (Division of Applied Chemistry and Biotechnology, Hanbat National University) ;
  • Lee, Bo-Hyun (Division of Applied Chemistry and Biotechnology, Hanbat National University) ;
  • Yeun, Go-Heum (Division of Applied Chemistry and Biotechnology, Hanbat National University) ;
  • Kim, Hyun-Ju (Division of Applied Chemistry and Biotechnology, Hanbat National University) ;
  • Won, Moo-Ho (Department of Neuroscience, Institute of Medical Sciences, School of Medicine, Kangwon National University) ;
  • Kim, Sang-Hern (Division of Applied Chemistry and Biotechnology, Hanbat National University) ;
  • Lee, Bong-Ho (Division of Applied Chemistry and Biotechnology, Hanbat National University) ;
  • Park, Jeong-Ho (Division of Applied Chemistry and Biotechnology, Hanbat National University)
  • Received : 2011.05.09
  • Accepted : 2011.06.21
  • Published : 2011.08.20
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Abstract

Polyphenols (PPs) are known as antioxidant compounds having benign biological activities. In this paper, a series of hybrid molecules between the free or acetyl protected polyphenol compounds were synthesized and their in vitro antioxidant activity (DPPH assay) and cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were evaluated. As expected, free phenolic hybrid compounds (6 and 8) showed better antioxidant activity than acetyl protected hybrid compounds (5 and 7) from DPPH assay. But the contrast result was obtained from BuChE inhibition assay. Acetyl protected hybrid compounds (5 and 7) showed better inhibition activity for BuChE than free phenolic hybrid compounds (6 and 8). Specifically, 10 (AcFA-AcFA) were shown as an effective inhibitor of BuChE ($IC_{50}=2.3{\pm}0.3{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 170 fold). Inhibition kinetic studies with acetyl protected compounds (5, 7, 9, and 10) indicated that 5, 7 and 10 are a hyperbolic mixed-type inhibition and 10 is a competitive inhibition type. The binding affinity (Ki) value of 10 to BuChE is $2.32{\pm}0.15{\mu}M$.

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References

  1. Loktionov, A. J. Nutr. Biochem. 2003, 14, 426. https://doi.org/10.1016/S0955-2863(03)00032-9
  2. Reich, D. E.; Lander, E. S. Trends Genet. 2001, 17, 502. https://doi.org/10.1016/S0168-9525(01)02410-6
  3. Viegas-Junior, C.; Danuello, A.; Silva Bolzani, V.; Barreiro, E. J.; Alberto, C.; Fraga, M. Current Medicinal Chemistry 2007, 14, 1829. https://doi.org/10.2174/092986707781058805
  4. Rosini, M.; Andrisano, V.; Bartolini, M.; Bolognesi, M. L.; Cavalli, A.; Minutesarini, A.; Recanatini, M.; Tumiatti, V.; Melchiorre, C. Sci. Pharm. 2005, 73, S37.
  5. Koufaki, M.; Calogeropoulou, T.; Detsi, A.; Roditis, A.; Kourounakis, A. P.; Papazafiri, P.; Tsiakitzis, K.; Gaitanaki, C.; Beis, I.; Kourounakis, P. N. J. Med. Chem. 2001, 44, 4300. https://doi.org/10.1021/jm010962w
  6. Rosini, M.; Andrisano, V.; Bartolini, M.; Bolognesi, M. L.; Hrelia, P.; Minutesarini, A.; Tarozzi, A.; Melchiorre, C. J. Med. Chem. 2005, 48, 360. https://doi.org/10.1021/jm049112h
  7. Ponpipom, M. M.; Bugianesi, R. L.; Blake, T. J. J. Med. Chem. 1987, 30, 705. https://doi.org/10.1021/jm00387a021
  8. 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
  9. Mei, Y.; Wei, D.; Liu, J. Cancer Biol. Ther. 2005, 4, 468. https://doi.org/10.4161/cbt.4.4.1698
  10. Jang, M.; Cai, L.; Udeani, G. O. Science 1997, 275, 218. https://doi.org/10.1126/science.275.5297.218
  11. Muldoon, M. F.; Kritchevsky, S. B. BMJ 1996, 312, 458. https://doi.org/10.1136/bmj.312.7029.458
  12. Zimmer, J.; Cooke, J. The Cardiovascular Cure: How to Strengthen Your Self-defense Against Heart Attack and Stroke; Broadway Books; New York, 2002.
  13. Owen, R. W.; Giacosa, A.; Hull, W. E.; Haubner, R.; Spiegelhalder, B.; Bartsch, H. Eur. J. Cancer 2000, 36, 1235. https://doi.org/10.1016/S0959-8049(00)00103-9
  14. Fito, M.; Covas, M. I.; Lamuela-Raventos, R. M. Lipids 2000, 35, 633. https://doi.org/10.1007/s11745-000-0567-1
  15. Vieira, O.; Escargueil-Blanc, I.; Meilhac, O. Br. J. Pharmacol. 1998, 123, 565. https://doi.org/10.1038/sj.bjp.0701624
  16. Seo, Y. M.; Nam, K. H.; Kang, P. S.; Ko, S. B. Oh, E.; Sung, M. T.; Choi, B. W.; Lee, B. H.; Park, J. H. Bull. Korean Chem. Soc. 2007, 28, 225. https://doi.org/10.5012/bkcs.2007.28.2.225
  17. Woo, Y. J.; Lee, B. H; Yeun, G. H.; Kim, H. J.; Ko, J. M.; Won, MH.; Lee, B. H.; Park, J. H. Bull. Korean Chem. Soc. in press.
  18. Goedert, M.; Spillantini, M. G. A. Science 2006, 314, 777. https://doi.org/10.1126/science.1132814
  19. Cumminutesgs, J. L. Rev. Neurol. Dis. 2004, 1, 60.
  20. Giacobini, E. Int. J. Geriatr. Psychiatry 2003, 18, S1. https://doi.org/10.1002/gps.935
  21. Mesulam, M.; Guillozet, A.; Shaw, P.; Levey, A.; Duysen, E.; Lockridge, O. Neuroscience 2002, 110, 627. https://doi.org/10.1016/S0306-4522(01)00613-3
  22. 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
  23. Darvesh, S.; Hopkins, D. A.; Geula, C. Nat. Rev. Neurosci. 2003, 4, 131. https://doi.org/10.1038/nrn1035
  24. Guillozet, A. L.; Smiley, J. F.; Mash, D. C.; Mesulam, M.-M. Ann Neurol. 1997, 42, 909. https://doi.org/10.1002/ana.410420613
  25. Yang, L.; He, H.-Y.; Zhang, X.-J. Neuroscience Research 2002, 42, 261 https://doi.org/10.1016/S0168-0102(02)00005-6
  26. Greig, N. H.; Utsuki, T.; Ingram, D. K.; Wang, Y.; Pepeu, G.; Scali, C.; Yu, Q. S.; Mamczarz, J.; Holloway, H. W.; Giordano, T.; Chen, D.; Furukawa, K.; Sambamurti, K.; Brossi, A.; Lahiri, D. K. Proc. Natl. Acad. Sci. 2005, 102, 17213. https://doi.org/10.1073/pnas.0508575102
  27. Chen, X.; Tikhonova, I. G.; Decker, M. Bioorg. Med. Chem. 2011, 19, 1222. https://doi.org/10.1016/j.bmc.2010.12.034
  28. Nawaz, S. A.; Ayaz, M.; Brandt, W.; Wessjohann, L. A.; Westermann, B. Biochem. Biophys. Res. Comm. 2011, 404, 935. https://doi.org/10.1016/j.bbrc.2010.12.084
  29. Wieckowska, A.; Bajda, M.; Guzior, N.; Malawska, B., Eu. J. Med. Chem. 2010, 45, 5602. https://doi.org/10.1016/j.ejmech.2010.09.010
  30. Huang, L.; Luo, Z.; He, F.; Shi, A.; Qin, F.; Li, X. Bioorg. Med. Chem. Letts 2010, 20, 6649. https://doi.org/10.1016/j.bmcl.2010.09.013
  31. Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.; Xikaitani, D.; Lien, E. J. J. Med. Chem. 1973, 16, 1207. https://doi.org/10.1021/jm00269a003
  32. Segel, I. H. Enzyme Kinetics; John Wiley & Sons: Inc., New York; 1975; pp 178-192.
  33. Ellman, G. L.; Coutney, K. D.; Andres, V. Jr.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88. https://doi.org/10.1016/0006-2952(61)90145-9

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