Bulletin of the Korean Chemical Society

  • 제34권4호
  • /
  • Pages.1025-1029
  • /
  • 2013
  • /
  • 0253-2964(pISSN)
  • /
  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
권호 표지
DOI QR코드

DOI QR Code

Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

  • Yeun, Go Heum (Department of Chemical & Biological Engineering, Hanbat National University) ;
  • Lee, Seung Hwan (Department of Chemical & Biological Engineering, Hanbat National University) ;
  • Lim, Yong Bae (Department of Chemical & Biological Engineering, Hanbat National University) ;
  • Lee, Hye Sook (Department of Chemical & Biological Engineering, Hanbat National University) ;
  • Won, Moo-Ho (Department of Neurobiology, School of Medicine, Kangwon National University) ;
  • Lee, Bong Ho (Department of Chemical & Biological Engineering, Hanbat National University) ;
  • Park, Jeong Ho (Department of Chemical & Biological Engineering, Hanbat National University)
  • 투고 : 2012.12.17
  • 심사 : 2013.01.03
  • 발행 : 2013.04.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between ${\alpha}$-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The $IC_{50}$ values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE ($IC_{50}=0.44{\pm}0.24{\mu}M$). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is $4.3{\pm}0.09{\mu}M$.

키워드

참고문헌

  1. Darvesh, S.; Hopkins, D.; Geula, C. Nat. Rev. Neurosci. 2003, 4, 131. https://doi.org/10.1038/nrn1035
  2. 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
  3. Greig, N.; Sambamurti, K.; Yu, Q.; Perry, T.; Holloway, H.; Haberman, F.; Brossi, A.; Ingram, D.; Lahiri, D. Butyrylcholinesterase: its selective inhibition and relevance to Alzheimer's disease. In Butyrylcholinesterase: Its Function and Inhibition; Giacobini, E., Ed.; Martin Dunitz: London, 2003; 69.
  4. 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
  5. Mesulam, M. M.; Geula, C. Ann. Neurol. 1994, 36, 722. https://doi.org/10.1002/ana.410360506
  6. 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
  7. Darvesh, S.; Hopkins, D. A.; Geula, C. Nat. Rev. Neurosci. 2003, 4, 131. https://doi.org/10.1038/nrn1035
  8. 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
  9. Li, B.; Duysen, E.; Carlson, M.; Lockridge, O. J. Pharmacol. Exp. Ther. 2008, 324, 1146.
  10. 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
  11. Ponpipom, M. M.; Bugianesi, R. L.; Blake, T. J. J. Med. Chem. 1987, 30, 705. https://doi.org/10.1021/jm00387a021
  12. 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
  13. Primo-Parmo, S.; Bartels, C.; Wiersema, B.; van der Spek, A.; Innis, J.; La Du, B. Am. J. Hum. Genet. 1996, 58, 52.
  14. Greig, N. H.; Lahiri, D. K.; Sambamurti, K. Int. Psychogeriatr. 2002, 14, 77. https://doi.org/10.1017/S1041610203008676
  15. Darras, F. H.; Kling, B.; Heilmann, J.; Decker, M. ACS Med. Chem. Lett. 2012, 3, 914. https://doi.org/10.1021/ml3001825
  16. Carolan, C. G.; Dillon, G. P.; Khan, D.; Ryder, S. A.; Gaynor, J. M.; Reidy, S.; Marquez, J. F.; Jones, M.; Holland, V.; Gilmer, J. F. J. Med. Chem. 2010, 53, 1190. https://doi.org/10.1021/jm9014845
  17. Decker, M.; Krauth, F.; Lehmann, J. Bioorg. Med. Chem. 2006, 14, 19661977. https://doi.org/10.1016/j.bmc.2005.10.044
  18. Decker, M. J. Med. Chem. 2006, 49, 5411. https://doi.org/10.1021/jm060682m
  19. Decker, M.; Kraus, B.; Heilmann, J. Bioorg. Med. Chem. 2008, 16, 4252. https://doi.org/10.1016/j.bmc.2008.02.083
  20. Viegas-Junior, C.; Danuello, A.; Silva Bolzani, V.; Barreiro, E. J.; Alberto, C.; Fraga, M. Curr. Med. Chem. 2007, 14, 1829. https://doi.org/10.2174/092986707781058805
  21. Loktionov, A. J. Nutr. Biochem. 2003, 14, 426. https://doi.org/10.1016/S0955-2863(03)00032-9
  22. Reich, D. E.; Lander, E. S. Trends Genet. 2001, 17, 502. https://doi.org/10.1016/S0168-9525(01)02410-6
  23. Rosini, M.; Andrisano, V.; Bartolini, M.; Bolognesi, M. L.; Cavalli, A.; Minarini, A.; Recanatini, M.; Tumiatti, V.; Melchiorre, C. Sci. Pharm. 2005, 73, S37.
  24. 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
  25. 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
  26. Woo, Y. J.; Lee, B. H.; Yeun, G. H.; Lee, J. E.; 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
  27. Woo, Y. J.; Lee, B. H.; Yeun, G. H.; Lee, 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
  28. 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
  29. 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

피인용 문헌

  1. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules vol.34, pp.11, 2013, https://doi.org/10.5012/bkcs.2013.34.11.3322
  2. Development of Cholinesterase Inhibitors using 1-Benzyl Piperidin-4-yl (α)-Lipoic Amide Molecules vol.35, pp.6, 2014, https://doi.org/10.5012/bkcs.2014.35.6.1681
  3. )-Allyl Cysteine Derivatives as a New-type Cholinesterase Inhibitor vol.36, pp.1, 2015, https://doi.org/10.1002/bkcs.10010
  4. Synthesis of Benzoisoxazole Derivatives and Evaluation of Inhibitory Potency against Cholinesterase for Alzheimer's Disease Therapeutics vol.37, pp.9, 2016, https://doi.org/10.1002/bkcs.10891
  5. Synthesis and in vitro Assay of New Triazole Linked Decursinol Derivatives Showing Inhibitory Activity against Cholinesterase for Alzheimer’s Disease Therapeutics vol.60, pp.2, 2016, https://doi.org/10.5012/jkcs.2016.60.2.125
  6. Design, synthesis, in vivo and in vitro studies of 1,2,3,4-tetrahydro-9H-carbazole derivatives, highly selective and potent butyrylcholinesterase inhibitors vol.24, pp.1, 2020, https://doi.org/10.1007/s11030-019-09943-6