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The Pharmaceutical Society of Korea (대한약학회)
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Synthesis of 6-[2-(Benzoxazol-2-ylmethylamino )ethoxy]-1-Alkyl­1 H-lndole-2-Carboxylic Acid and Inhibitory Activity on $\beta$-Amyloid Aggregation

  • Lee, Sun-Mi (College of Pharmacy, Sookmyung Women's University) ;
  • Jeon, Raok (College of Pharmacy, Sookmyung Women's University)
  • Published : 2005.11.01
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Abstract

6-[2-(Benzoxazol-2-ylmethylamino)ethoxy]-1-alkyl-1H-indole-2-carboxylic acids were designed and synthesized as $\beta$-amyloid (A$\beta$) fibril assembly inhibitors. Their inhibitory activity on A$\beta$, aggregation was evaluated by thioflavin T assay although their activities were insignificant.

Keywords

References

  1. Endoh, M., Kunishita, T., and Tabira, T., No effect of anti-leprosy drugs in the prevention of Alzheimer's disease and $\beta$-amyloid neurotoxicity. J., Neurol. Sci., 165, 28-30 (1999) https://doi.org/10.1016/S0022-510X(99)00057-X
  2. Hardy, J. and Allsop, D., Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol. Sci., 12, 383-388 (1991) https://doi.org/10.1016/0165-6147(91)90609-V
  3. Howlett, D. R., Perry, A. E., Godfrey, F., Swatton, J. E., Jennings, K. H., Spitzfaden, C., Wadsworth, H., Wood, S. J., and Markwell, R. E., Inhibition of fibril formation in $\beta$-amyloid peptide by a novel series of benzofurans. Biochemi. J., 340, 283-289 (1999) https://doi.org/10.1042/0264-6021:3400283
  4. Iversen, L. L., Mortishire-Smith, R. J., Pollack, S. J., and Shearman, M. S., The toxicity in vitro of $\beta$-amyloid protein. Biochemi. J., 311, 1-16 (1995) https://doi.org/10.1042/bj3110001
  5. Kim, H. and Jeon, R., Synthesis of {5-[2-(benzoxazol-2-yl-methylamino)ethoxy]-1-methylindol-3-yl}acetic acid and inhibitory activity on $\beta$-amyloid aggregation. J. Pharmaceutical Sciences, Sookmyung Women's Univ., 21, 63-66 (2004).
  6. LeVine, H., The Challenge of Inhibiting Abeta Polymerization. Curr. Med. Chem., 9, 1121-1134 (2002) https://doi.org/10.2174/0929867023370167
  7. Roher, A. E., Baudry, J., Chaney, M. O., Kuo, Y.-M., Stine, W. B., and Emmerling, M. R., Oligomerization and fibril assembly of the amyloid-$\beta$ protein. Biochim. Biophys. Acta 1502, 31-43 (2000) https://doi.org/10.1016/S0925-4439(00)00030-2
  8. Selkoe, D. J., Translating cell biology into therapeutic advances in Alzheimer's disease. Nature, 399, A23-A31 (1999) https://doi.org/10.1038/19866
  9. Serpell, L. C., Alzheimer's amyloid fibrils: structure and assembly. Biochim. Biophys. Acta, 1502, 16-30 (2000) https://doi.org/10.1016/S0925-4439(00)00029-6
  10. Tomiyama, T., Kaneko, H., Kataoka, K., Asano, S., and Endo, N., Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to peptide fibrils and preventing amyloidcell interaction. Biochem. J., 322, 859-865 (1997) https://doi.org/10.1042/bj3220859
  11. Tomiyama, T., Shoji, A., Kataoka, K., Suwa, Y., Asano, S., Kaneko, H., and Endo, N., Inhibition of Amyloid Protein Aggregation and Neurotoxicity by Rifampicin. J. Biol. Chem., 271, 6839- 6844 (1996) https://doi.org/10.1074/jbc.271.12.6839
  12. Walsh, D. M., Hartley, D. M., Kusumoto, Y., Fezoui Y., Condron, M. M., Lomakin, A., Benedek, G. B., Selkoe, D. J., and Teplow, D. B., Amyloid $\beta$-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J. Biol. Chem., 274, 25945-25952 (1999) https://doi.org/10.1074/jbc.274.36.25945
  13. Yankner, B. A., Dawes, L. R.. Fisher, S., Villa-Komaroff, L., Oster- Granite, M. L., and Neve, R. L., Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science, 245, 417-420 (1989) https://doi.org/10.1126/science.2474201