Abstract
An allergic reaction ensues after antigen binds to mast cell or basophil high affinity IgE receptor, FcεRI, resulting in degranulation of various inflammatory mediators that produce various allergic symptoms. In this study, i) we isolated the active component for the inhibition of mast cell degranulation from the extract of leaves ofCastanea crenata and identified it as quercetin; ii) we established the total synthesis procedure of quercetin; iii) using quercetin as positive control, we excavated some lead compounds that possess inhibitory activities for mast cell degranulation by screening the chemical libraries of 1,3-oxazolidine derivatives prepared by solid phase combinatorial chemistry. Some of 1,3-oxazolidine compounds possessing acetyl and 3′,4′-dichlorophenyl group displayed strong inhibitory activities on FcεRI-mediated mast cell degranulation, suggesting that they can be used as lead compounds for the development of anti-allergic agents.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blank, U., Ra, C., Miller, L., White, K., Metzger, H., and Kinet, J. P., Complete structure and expression in transfected cells of high affinity IgE receptor.Nature, 337, 187–189 (1989).
Cambier, J. C., Antigen and Fc receptor signaling. The awesome power of the immunoreceptor tyrosine-based activation motif (ITAM).J. Immunol., 155, 3281–3285 (1995).
Cheong, H., Ryu, S. Y., and Kim, K. M., Anti-allergic action of resveratrol and related hydroxystilbenes.Plants Med., 65, 266–268 (1999).
Cheong, H., Ryu, S. Y., Oak, M. H., Cheon, S. H., Yoo, G. S., and Kim, K. M., Studies of structure activity relationship of flavonoids for the anti-allergic actions.Arch. Pharm. Res., 21, 478–480 (1989).
Cox, J. S., Disodium cromoglycate (FPL 670) (‘Intel’): a specific inhibitor of reaginic antibody-antigen mechanisms.Nature, 216, 1328–1329 (1967).
Fischer, M. J., Paulussen, J. J., Horbach, D. A., Roelofsen, E. P., van Miltenburg, J. C., de Mol, N. J., and Janssen, L. H., Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.Inflamm. Res., 44, 92–97 (1995).
Kinet, J. P., The high-affinity receptor for IgE.Curr. Opin. Immunol., 2, 499–505 (1989).
Lee, E., Choi, E. J., Cheong, H., Kim, Y. R., Ryu, S. Y., and Kim, K. M., Anti-allergic actions of the leaves of Castanea crenata and isolation of an active component responsible for the inhibition of mast cell degranulation.Arch. Pharm. Res., 22, 320–323 (1999).
Oh, H. S., Hahn, H. G., Cheon, S. H., and Ha, D. C., Solid phase synthesis of 1,3-oxazolidine derivatives.Tetrahedron Lett., 41, 5069–5072 (2000).
Reth, M., Antigen receptor tail clue.Nature, 338, 383–384 (1989).
Rivera, J., Molecular adapters in Fc(epsilon)RI signaling and the allergic response.Curr. Opin. Immunol., 14, 688–693 (2002).
Schwartz, L. B., Austen, K. F., and Wasserman, S. I., Immunologic release of beta-hexosaminidase and beta-glucuronidase from purified rat serosal mast cells.J. Immunol., 123, 1445–1450 (1979).
Thompson, L. A. and Ellman, J. A., Synthesis and applications of small molecule libraries.Chem. Rev., 96, 555–600 (1996).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hahn, HG., Oh, H.S., Cheon, S.H. et al. Excavation of lead compounds that inhibit mast cell degranulation by combinatorial chemistry and activity-guided. Arch Pharm Res 27, 518–523 (2004). https://doi.org/10.1007/BF02980125
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02980125