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Development of Selective Butyrylcholinesterase Inhibitors Using (R)-Lipoic Acid-Polyphenol Hybrid Molecules

  • Woo, Yeun-Ji ;
  • Lee, Bo-Hyun ;
  • Yeun, Go-Heum ;
  • Kim, Hyun-Ju ;
  • Ko, Jang-Myoun ;
  • Won, Moo-Ho ;
  • Lee, Bong-Ho ;
  • Park, Jeong-Ho
  • Received : 2011.02.25
  • Accepted : 2011.04.17
  • Published : 2011.08.20

Abstract

A series of hybrid molecules between (R)-lipoic acid (ALA) and the acetylated or methylated polyphenol compounds were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were checked. The $IC_{50}$ values of all hybrid molecules for a BuChE inhibition were lower than those of the single parent compounds. Specifically, ALA-acetyl protected caffeic acid (11, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.5{\pm}0.2\;{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 800 fold). Inhibition kinetic study indicated that 11 is a mixed inhibition type. Its binding affinity ($K_i$) value to BuChE is $1.52{\pm}0.18\;{\mu}M$.

Keywords

Molecular hybridization;(R)-Lipoic acid;Polyphenols;Cholinesterase inhibitor

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.; Minarini, 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.; Minarini, 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. 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
  10. Evans, J. L.; Goldfine, I. D. Diabetes Technol. Ther. 2000, 2, 401. https://doi.org/10.1089/15209150050194279
  11. Scott, B. C.; Aruoma, O. I.; Evans, P. J.; O'Neill, C.; Van, d. V.; Cross, C. E.; Trischler, H.; Halliwell, B. Free Rad. Res. 1994, 20, 119. https://doi.org/10.3109/10715769409147509
  12. Deneke, S. M. Curr. Top. Cell Regul. 2000, 36, 151.
  13. Randle, P. J. Diabetes Metab. Rev. 1998, 14, 263. https://doi.org/10.1002/(SICI)1099-0895(199812)14:4<263::AID-DMR233>3.0.CO;2-C
  14. Suh, J. H.; Zhu, B. Z.; deSzoeke, E.; Frei, B.; Hagen, T. M. Redox Rep. 2004, 9, 57. https://doi.org/10.1179/135100004225003923
  15. Matsugo, S.; Yan, L. J.; Han, D.; Trischer, H. J.; Packer, L. Biochem. Biophys. Res. Commun. 1995, 208, 161. https://doi.org/10.1006/bbrc.1995.1318
  16. Packer, L.; Witt, E. H.; Tritschler, H. J. Free Rad. Biol. Med. 1995, 19, 227. https://doi.org/10.1016/0891-5849(95)00017-R
  17. Biewenga, G. P.; Haenen, G. R. M. M.; Bast, A. Gen. Pharmac. 1997, 29, 315. https://doi.org/10.1016/S0306-3623(96)00474-0
  18. Borcea, V.; Nourooz-Zadeh, J.; Wolff, S. P.; Klevesath, M.; Hofmann, M.; Urich, H.; Wahl, P.; Ziegler, R.; Tritshler, H.; Halliwell, B.; Nawroth, P. P. Free Rad. Biol. Med. 1999, 26, 1495. https://doi.org/10.1016/S0891-5849(99)00011-8
  19. Freisleben, H. J. Toxicology 2000, 148, 159. https://doi.org/10.1016/S0300-483X(00)00207-9
  20. Maitra, I.; Serbinova, E.; Trischler, H.; Packer, L. Free Rad. Biol. Med. 1995, 18, 823. https://doi.org/10.1016/0891-5849(94)00195-P
  21. Packer, L.; Trischler, H.; Wessel, K. Free Rad. Biol. Med. 1997, 22, 359. https://doi.org/10.1016/S0891-5849(96)00269-9
  22. Farr, S. A.; Poon,; Dogrukol-Ak, D.; Drake, J.; Banks, W. A.; Eyerman, E.; Butterfield, D. A.; Morley, J. E. J. Neurochem. 2003, 84, 1173. https://doi.org/10.1046/j.1471-4159.2003.01580.x
  23. Hager, K.; Marahrens, A.; Kenklies, M.; Riederer, P.; Munch, G. Arch. Gerontol. Geriatr. 2001, 32, 275. https://doi.org/10.1016/S0167-4943(01)00104-2
  24. Midaouri, A. E.; Elimadi, A.; Wu, L.; Haddad, P. S.; de Champlain, J. Hypertens. 2003, 16, 173. https://doi.org/10.1016/S0895-7061(02)03253-3
  25. Di Stefano, A.; Sozio, P.; Cocco, A.; Iannitelli, A.; Santucci, E.; Costa, M.; Pecci, L.; Nasuti, C.; Cantalamessa, F.; Pinnen, F. J. Med. Chem. 2006, 23, 1486.
  26. Koufaki, M.; Calogeropoulou, T.; Detsi, A.; Roditis, A.; Kourounakis, A. P.; Papaza.ri, P.; Tsiakitzis, K.; Gaitanaki, C.; Beis, I.; Kourounakis, P. N. J. Med. Chem. 2001, 44, 4300. https://doi.org/10.1021/jm010962w
  27. Durand, G.; Polidori, A.; Salles, J.-P.; Pucci, B. Bioorg. Med. Chem. Lett. 2003, 13, 859. https://doi.org/10.1016/S0960-894X(02)01079-X
  28. Durand, G.; Polidori, A.; Salles, J. P.; Prost, M.; Durand, P.; Pucci, B. Bioorg. Med. Chem. Lett. 2003, 13, 2673. https://doi.org/10.1016/S0960-894X(03)00545-6
  29. Harnett, J. J.; Auguet, M.; Viossat, I.; Dolo, C.; Bigg, D.; Chabrier, P.-E. Bioorg. Med. Chem. Lett. 2002, 12, 1439. https://doi.org/10.1016/S0960-894X(02)00216-0
  30. Guillonneau, C.; Charton, Y.; Ginot, Y-M.; Fouquier-d'Herouel, M.-V.; Bertrand, M.; Lockhart, B.; Lestage, P.; Goldstein, S. Eur. J. Med. Chem. 2003, 38, 1. https://doi.org/10.1016/S0223-5234(02)01424-1
  31. 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
  32. Melagraki, G.; Afantitis, A.; Igglessi-Markopoulou, O.; Detsi, A.; Koufaki, M.; Kontogiorgis, C.; Hadjipavlou-Litina, D. J. Eur. J. Med. Chem. 2009, 44, 3020. https://doi.org/10.1016/j.ejmech.2008.12.027
  33. Decker, M.; Kraus, B.; Heilmann, J. Bioorg. Med. Chem. 2008, 16, 4252. https://doi.org/10.1016/j.bmc.2008.02.083
  34. Koufaki, M.; Kiziridi, C.; Alexi, X.; Alexis, M. N. Bioorg. Med. Chem. 2009, 17, 6432. https://doi.org/10.1016/j.bmc.2009.07.010
  35. Mei, Y.; Wei, D.; Liu, J. Cancer Biol. Ther. 2005, 4, 468. https://doi.org/10.4161/cbt.4.4.1698
  36. Jang, M.; Cai, L.; Udeani, G. O. Science 1997, 275, 218. https://doi.org/10.1126/science.275.5297.218
  37. Muldoon, M. F.; Kritchevsky, S. B. BMJ 1996, 312, 458. https://doi.org/10.1136/bmj.312.7029.458
  38. Zimmer, J.; Cooke, J. The Cardiovascular Cure: How to Strengthen Your Self-defense against Heart Attack and Stroke; New York, Broadway Books: 2002
  39. 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
  40. Fito, M.; Covas, M. I.; Lamuela-Raventos, R. M. Lipids 2000, 35, 633. https://doi.org/10.1007/s11745-000-0567-1
  41. Vieira, O.; Escargueil-Blanc, I.; Meilhac, O. Br. J. Pharmacol. 1998, 123, 565. https://doi.org/10.1038/sj.bjp.0701624
  42. Darvesh, S.; Hopkins, D.; Geula, C. Nat. Rev. Neurosci. 2003, 4, 131. https://doi.org/10.1038/nrn1035
  43. Bazelyansky, M.; Robey, E.; Kirsch, J. F. Biochem. 1986, 25, 125. https://doi.org/10.1021/bi00349a019
  44. Greig, N. H.; Utsuki, T.; Yu, Q.; Zhu, X.; Holloway, H. W.; Perry, T.; Lee, B.; Ingram, D. K.; Lahiri, D. K. Curr. Med. Res. Opin. 2001, 17, 1. https://doi.org/10.1185/03007990152005397
  45. Greig, N. H.; Sambamurti, K.; Yu, Q. S.; Greig, N.; Sambamurti, K.; Yu, Q.; Perry, T.; Holloway, H.; Haberman, F.; Brossi, A.; Ingram, D.; Lahiri, D. In Butyrylcholinesterase: Its Function and Inhibition; Giacobini, E., Ed.; Martin Dunitz: London, 2003; 69.
  46. 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
  47. Mesulam, M. M.; Geula, C. Ann. Neurol. 1994, 36, 722 https://doi.org/10.1002/ana.410360506
  48. 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
  49. Darvesh, S.; Hopkins, D. A.; Geula, C. Nat. Rev. Neurosci. 2003, 4, 131. https://doi.org/10.1038/nrn1035
  50. 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. PNAS. 2005, 102, 17213. https://doi.org/10.1073/pnas.0508575102
  51. Li, B.; Duysen, E.; Carlson, M.; Lockridge, O. J. Pharmacol. Exp. Ther. 2008, 324, 1146.
  52. Primo-Parmo, S.; Bartels, C.; Wiersema, B.; van der Spek, A.; Innis, J.; La Du, B. Am. J. Hum. Genet. 1996, 58, 52
  53. Greig, N. H.; Lahiri, D. K.; Sambamurti, K. Int. Psychogeriatr. 2002, 14, 77. https://doi.org/10.1017/S1041610203008676
  54. 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
  55. 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
  56. Basran, J.; Mewies, M.; Mathews, F. S.; Scrutton, N. S. Biochem. 1997, 36, 1989. https://doi.org/10.1021/bi962623o
  57. Greig, N. H.; Utsuki, T.; Ingram, D. K.; Wang, Y.; Pepeu, G.; Scali, C.; Yu, Q.-S.; Mamczarz, J.; Harold W. Holloway, 111h. W.; Giordano, T.; Chen, D.; Furukawa, K.; Sambamurti, K.; Brossi, A.; Lahiri, D. K. PNAS 2005, 102, 17213. https://doi.org/10.1073/pnas.0508575102
  58. Brossi, A. J. Med. Chem. 1990, 33, 2311. https://doi.org/10.1021/jm00171a001

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