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Flavonoids as potential inhibitors of retroviral enzymes

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Abstract

Flavonoids are abundant in plants as secondary metabolites where they have antioxidant activities. The diverse and non-specific inhibition of several enzymes, including avian myeloblastosis virus reverse transcriptase (RT), human immunodeficiency virus (HIV) RT, murine leukemia virus RT, HIV-1 protease, trypsin and elastase, were tested for by observing the effects of several flavonoid compounds. Some of the flavonoids were reconfirmed as antiretroviral agents as previously shown by others. Flavonoids belonging to the flavonol or flavone group simultaneously inhibited reverse transcriptases and proteases. On the contrary, flavonoids belonging to the flavanol, isoflavone or flavanone group were less likely to inhibit reverse transcriptase or protease. Vegetables and fruits rich in flavonoids have become integral and even necessary in the animal diet, suggesting that flavonoids may have developed to play beneficiary roles for not only the plants themselves but also the predator animals.

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Abbreviations

AMV:

avian myeloblastosis virus

ATA:

aurintricarboxylic acid

DTT:

dithiothreitol

dTTP:

deoxythymidine triphosphate

EDTA:

ethylenediaminetetraacetic acid

FRET:

fluorescence resonance energy transfer

HIV:

human immunodeficiency virus

IC50 :

half maximal inhibitory concentration

MuLV:

murine leukemia virus

RT:

reverse transcriptase

References

  • Ahn EM, Han JT, Kwon BM, Kim SH, and Baek NI (2008) Anti-cancer activity of flavonoids from Aceriphyllum rossii. J Korean Soc Appl Biol Chem 51, 309–315.

    Article  CAS  Google Scholar 

  • Ahn MJ, Yoon KD, Min SY, Lee JS, Kim JH, Kim TG, Kim SH, Kim NG, Huh H, and Kim JW (2004) Inhibition of HIV-1 reverse transcriptase and protease by phlorotannins from the brown alga Ecklonia cava. Biol Pharm Bull 27, 544–547.

    Article  CAS  Google Scholar 

  • Baltimore D (1970) Viral RNA dependent DNA polymerase: RNA dependent DNA polymerase in virions of RNA tumour viruses. Nature 226, 1209–1211.

    Article  CAS  Google Scholar 

  • Brinkworth RI, Martin JS, and David PF (1992) Flavones are inhibitors of HIV-1 proteinase. Biochem Biophys Res Commun 188, 631–637.

    Article  CAS  Google Scholar 

  • Coffin JM (1996) Retroviridae and their replication. In Virology, Fields BN et al. (eds.) pp. 1767–1848. Raven Press, NY, U.S.A.

    Google Scholar 

  • Häkkinen SH, Kärenlampi SO, Heinonen IM, Mykkänen HM, and Törrönen AR (1999) Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J Agric Food Chem 47, 2274–2279.

    Article  Google Scholar 

  • Kaul TN, Elliott Middleton Jr MD, and Pearay LO (1985) Antiviral effect of flavonoids on human viruses. J Med Virol 15, 71–79.

    Article  CAS  Google Scholar 

  • Kohlstaedt LA, Wang J, Friedman JM, Rice PA, and Steitz TA (1992) Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256, 1783–1790.

    Article  CAS  Google Scholar 

  • Lin YM, Herbert A, Michael TF, Yeah-Huei SP, Eugenia MG, Thitima P, John MP, Raymond FS, Stephen HH, and Fa-Ching C (1997) In Vitro Anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora. J Nat Prod 60, 884–888.

    Article  CAS  Google Scholar 

  • Luciw PA and Leung NJ (1992) Mechanisms of retrovirus replication. In The Retroviridae: Levy JA (ed.) pp. 159–298. Plenum Press, NY, U.S.A.

    Chapter  Google Scholar 

  • Ma SC, But PP, Ooi VE, He YH, Lee SH, Lee SF, and Lin RC (2001) Antiviral amentoflavone from Selaginella sinensis. Biol Pharm Bull 24, 311–312.

    Article  CAS  Google Scholar 

  • Moore PS and Pizza C (1992) Observations on the inhibition of HIV-1 reverse transcriptase by catechins. Biochem J 288, 717–719.

    CAS  Google Scholar 

  • Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, and van Leeuwen PA (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74, 418–425.

    CAS  Google Scholar 

  • Pan X, Tan N, Zeng G, Zhang Y, and Jia R (2005) Amentoflavone and its derivatives as novel natural inhibitors of human cathepsin B. Bioorg Med Chem 13, 5819–5825.

    Article  CAS  Google Scholar 

  • Pietta PG (2000) Flavonoids as antioxidants. J Nat Prod 63, 1035–1042.

    Article  CAS  Google Scholar 

  • Sarafianos SG, Kortz U, Pope MT, and Modak MJ (1996) Mechanism of polyoxometalate-mediated inactivation of DNA polymerases: an analysis with HIV-1 reverse transcriptase indicates specificity for the DNA-binding cleft. Biochem J 319, 619–626.

    CAS  Google Scholar 

  • Seelmeier SH, Schmidt VT, and von der Helm K (1988) Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci 85, 6612–6616.

    Article  CAS  Google Scholar 

  • Song MC, Yang HJ, Kim DK, Jeong TS, Kwon BM, Kim JP, Park SK, and Baek NI (2008) Bioactive flavonoids from Trapa pseudoincisa. J Korean Soc Appl Biol Chem 51, 334–337.

    Article  CAS  Google Scholar 

  • Spedding G, Ratty A, and Middleton E Jr (1989) Inhibition of reverse transcriptase by flavonoids. Antivir Res 12, 99–110.

    Article  CAS  Google Scholar 

  • Spence RA, Kati WM, Anderson KS, and Johnson KA (1995) Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 267, 988–993.

    Article  CAS  Google Scholar 

  • St. Clair MH, Martin JL, Tudor-Williams G, Bach MC, Vavro CL, King DM, Kellam P, Kemp SD, and Larder BA (1991) Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 253, 1557–1559.

    Article  CAS  Google Scholar 

  • Temin HM and Mizutani S (1970) Viral RNA dependent DNA polymerase: RNA dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226, 1211–1213.

    Article  CAS  Google Scholar 

  • Tanese N and Goff SP (1988) Domain structure of the Moloney murine leukemia virus reverse transcriptase: mutational analysis and separate expression of the DNA polymerase and RNase H activities. Proc Natl Acad Sci 85, 1777–1781.

    Article  CAS  Google Scholar 

  • Williamson MP, McCormick TG, Nance CL, and Shearer WT (2006) Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: potential for HIV-1 therapy. J Allergy Clin Immunol 118, 1369–1374.

    Article  CAS  Google Scholar 

  • Yu YB (2004) The Extracts of Solanum nigrum L. for inhibitory effects on HIV-1 and its essential enzymes. Korean J Orient Med 10, 119–126.

    Google Scholar 

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Correspondence to Young Hwan Ko.

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Ko, YJ., Oh, HJ., Ahn, HM. et al. Flavonoids as potential inhibitors of retroviral enzymes. J. Korean Soc. Appl. Biol. Chem. 52, 321–326 (2009). https://doi.org/10.3839/jksabc.2009.057

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  • DOI: https://doi.org/10.3839/jksabc.2009.057

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