Neuraminidase Inhibitors fromReynoutria elliptica
Research Articles Articles
In the course of screening neuraminidase inhibitors from herbal medicines, Reynoutria elliptica exhibited high inhibitory activity. Four active compounds were isolated from the ethyl acetate soluble fraction by consecutive purification using sillica gel, Sephadex LH-20 chromatography, and recrystallization. The chemical structures of these compounds were identified as 1,3,8-trihy-droxy-6-methylanthraquinone (emodin) 1,8-dihydroxy-3-methoxy-6-methylanthraquinone (emodin 3-methyl ether; physcion), 1,3,8-trihydroxy-6-hydoxymethylanthraquinone (ω-hydroxyemodin), and 3,5,4′-trihydroxystilbene (trans-resvertrol) by spectral data including MS,1 H-, and13 C-NMR. The IC50 values of emodin, emodin 3-methyl ether, ω-hydroxyemodin, andtrans-resvertrol were 2.81, 74.07, 10.49, and 8.77 μM, respectively. They did not inhibit other glycosidase such as glucosidase, mannosidase, and galactosidase, indicating that they were relatively specific inhibitors of neuraminidase.
Key wordsNeuraminidase inhibitor Influenza Emodin Emodin 3-methyl ether Physcion ω-Hydroxy emodin trans-Resveratrol Reynoutria elliptica
Burmeister, W. P., Ruigrok, R. W., and Cusack, S., The 2.2 resolution crystal structure of influenza B neuraminidase and its complex with sialic acid.EMBO J.
, 11, 49–56 (1992).PubMedGoogle Scholar
Chen, L., Han, Y., Yang, F., and Zhang, T., High-speed counter-current chromatography separation and purification resver-trol and piceidPolygonum cuspidatum
.J. Chromatogr A.
, 907, 343–346 (2001).PubMedCrossRefGoogle Scholar
Colman, P. M., Influenza virus neuraminidase: structure, antibiotics and inhibitors.Protein Sci.
, 3, 1687–1696 (1994).PubMedCrossRefGoogle Scholar
Colman, P. M., Design and antiviral properties of influenza virus neuraminidase inhibitors.Pure Appl. Chem.
, 67, 1683–1688 (1995).CrossRefGoogle Scholar
Colman, P. M., A novel approach to antiviral to therapy for influenza.J. Antimicrob. Chemother
, 44, 17–22 (1999).PubMedCrossRefGoogle Scholar
Francis, G. W., Aksnes, D. W., and Holt, Q., Assignment of the1
C NMR spectra of anthraquinone glycoside fromRhamnus frangula
.Mag. Res. Chem.
, 36, 769–772 (1998).CrossRefGoogle Scholar
Gottschalk, A., The specific enzyme of influenza virus andVibrio cholerae
.Biochem. Biophys. Acta.
, 23, 645–646 (1957).PubMedCrossRefGoogle Scholar
Klenk, H. O. and Rott, R., The molecular biology of influenza virus pathogenicity.Adv. Virus Res.
, 34, 247–280 (1988).PubMedCrossRefGoogle Scholar
Ko, S. K., Whang, W. K., and Kim, I. H., Anthraquinone and stilbene derivatives from the cultivated Korean Rhubarb Rhizomes.Arch. Pharm. Res.
, 18, 282–288 (1995).CrossRefGoogle Scholar
Lin, C., Eichelberger, M. C., Compans, R. W., and Air, G. M., Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly or budding.J. Virol.
, 69, 1099–1106 (1995).Google Scholar
Likhitwitayawuid, K., Sritularak, B., and De-Eknamkul, W., Tyrosinase inhibitors fromArtocarpus gomezianus
, 66, 275–277 (2000).PubMedCrossRefGoogle Scholar
Murakami, H., Kobayashi, J., Musuda, T., Morooka, N., and Ueno, Y., ω-Hydroxyemodin, a major hepatic metabolite of emodin in various animals and its mutagenic activity.Mutation Res.
, 180, 147–153 (1987).PubMedGoogle Scholar
Myers, R. W., Lee, R. T., Lee, Y. C., and Thomas, G. H., The synthesis of 4-methylumberiferyl α-ketoside ofN
-acetyl-neuraminic acid and its use in a fluorometric assay for neuraminidase.Anal. Biochem.
, 101, 166–174 (1980).PubMedCrossRefGoogle Scholar
Palese, P. and Compans, R. W., Inhibition of influenza virus replication in tissue culture by 2-deoxy-2, 3-dehydro-N
-trifluoroacetyl neuraminic acid (FANA): mechanism of action.J. General Virol.
, 33, 159–163 (1976).CrossRefGoogle Scholar
Palese, P., Tabita, U., Ueda, M., and Compans, R. W., Characterization of temperature sensitive influenza virus mutants.Virology
, 61, 397–410 (1974).PubMedCrossRefGoogle Scholar
Varghee, J. N., Mckimm-Breschkin, J. L., Caldwell, J. B., Kortt, A. A., and Colman, P. M., The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor.Protein
, 14, 327–332 (1992).CrossRefGoogle Scholar
von Itzstein, N., Kok, G. B., and Pegg, M. S., Rational design of potent sialidase-based inhibitors of influenza virus replication.Nature
, 363, 418–423 (1993).CrossRefGoogle Scholar
Willey, D. C. and Skehel, J. J., The structure and function of the hemagglutinin membrane glycoprotein of influenza virus.Annu. Rev. Biochem.
, 56, 365–394 (1987).CrossRefGoogle Scholar
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