Archives of Pharmacal Research

  • 제28권7호
  • /
  • Pages.799-803
  • /
  • 2005
  • /
  • 0253-6269(pISSN)
  • /
  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

[ $\beta$ ]-Secretase (BACE1) Inhibitors from Sanguisorbae Radix

  • Lee, Hee-Ju (School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Seong, Yeon-Hee (College of Veterinary Medicine, Chungbuk National University) ;
  • Bae, Ki-Hwan (College of Pharmacy, Chungnam National University) ;
  • Kwon, Soon-Ho (School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Kwak, Hye-Min (School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Nho, Si-Kab (Department of Natural Fiber Science, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Kim, Kyung-A (Department of Natural Fiber Science, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Hur, Jong-Moon (School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Lee, Kyung-Bok (Department of Biochemistry, School of Medicine, Konyang University) ;
  • Kang, Young-Hwa (School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Song, Kyung-Sik (School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University)
  • 발행 : 2005.07.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

In the course of screening anti-dementia agents from natural products, two $\beta$-secretase (BACE1) inhibitors were isolated from the ethyl acetate soluble fraction of Sanguisorbae Radix by the activity-guided purification using silica gel, Sephadex LH-20, and RP-HPLC. They were identified as 1,2,3-trigalloyl-4,6-hexahydroxydiphenoyl-$\beta$-D-glucopyranoside (Tellimagrandin II, 1) and 1,2,3,4,6-pentagalloyl-$\beta$-D-glucopyranoside (2) and were shown to non-competitively inhibit $\beta$-secretase (BACE1) with the $IC_{50}$ values of $3.10{\times}10^{-6}M\;and\;3.76{\times}10^{-6}M$, respectively. The Ki values of 1 and 2 were $6.84{\times}10^{-6}M\;and\;5.13{\times}10^{-6}M$. They were less inhibitory to asecretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.

키워드

참고문헌

  1. Anderson, J. P., Barbour, R., Basi, G. S., Caccavello, R., Davis, D., and Doan, M. et al., Purification and cloning of amyloid precursor protein $\beta$-secretase from human brain. Nature, 402, 533-537 (1999) https://doi.org/10.1038/990107
  2. Citron, M., $\beta$-Secretase as a target for the treatment of Alzheimer's disease. J. Neurosci. Res., 70, 373-379 (2002) https://doi.org/10.1002/jnr.10393
  3. Feldman, K. S. and Sahasrabudhe, K., Ellagitannin Chemistry. Syntheses of tellimagrandin and a dehydrodigalloyl ethercontaining dimeric gallotannin analogue of coriariin A. J. Org. Chem., 64, 209-216 (1999) https://doi.org/10.1021/jo9816966
  4. Ghosh A. K., Bilcer G., Harwood C., Kawahama R., Shin, D., Hussain, K. A., Hong, L., Loy, J. A., Nguyen, C., Koelsch, G., Ermolieff, J., and Tang, J., Structure-based design: potent inhibition of human brain memapsin 2 ($\beta$-secretase). J. Med. Chem., 44, 2865-2868 (2001) https://doi.org/10.1021/jm0101803
  5. Ghosh, A. K., Shin, D., Downs, D., Koelsch, G., Lin, X., Ermolieff, J., and Tang, J., Design of potent inhibitors for human brain memapsin 2 ($\beta$-secretase). J. Am. Chem. Soc., 122, 3522- 3523 (2000) https://doi.org/10.1021/ja000300g
  6. Glenner, G. G. and Wong, C. W., Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun., 120, 885-890 (1984) https://doi.org/10.1016/S0006-291X(84)80190-4
  7. Jeon, S.-Y., Bae, K-.H., Seong, Y.-H., and Song, K.-S., Green tea catechins as a BACE1 ($\beta$-secretase) inhibitor. Bioorg. Med. Chem. Lett., 13, 3905-3908 (2003) https://doi.org/10.1016/j.bmcl.2003.09.018
  8. Kim, S.-I. and Song, K.-S., 1,2,3,4,6-Pentagalloyl-$\beta$-D-glucopyranose, a prolyl endopeptidase inhibitor from Moutan cortex. J. Korean Soc. Agric. Chem. Biotechnol., 43, 158-161 (2000)
  9. Lee, V. M.-Y., Balin, B. J., Otvos, L., and Trojanowski, J. Q., A major subunit of paired helical filaments and derivatized forms of normal tau. Science, 251, 675-678 (1991) https://doi.org/10.1126/science.1899488
  10. Terry, R. D., Masliah, E., and Hansen, L. A., The neuropathology of Alzheimer disease and the structural basis of its cognitive alterations, in: R. D. Terry et al. (Ed.), Alzheimer Disease, Lippincott, Williams and Wilkins, Philadelphia, pp. 187-206 (1999)
  11. Tung J. S., Davis D. L., Anderson J. P., Walker D. E., Mamo S., Jewett N., Hom R. K., Sinha S., Thorsett E. D., and John V., Design of substrate-based inhibitors of human $\beta$-secretase. J. Med. Chem., 45, 259-262, (2002) https://doi.org/10.1021/jm0155695
  12. Vassar, R., $\beta$-Secretase (BACE) as a drug target for alzheimer's disease. Advanced Drug Delivery Reviews, 54, 1589-1602 (2002) https://doi.org/10.1016/S0169-409X(02)00157-6