Abstract
Aryl diketoacid (ADK) is well known for antiviral activity which can be enhanced by introduction of an aromatic arylmethyl substituent. A natural flavonoid quercetin has a 3,5-dihydroxychromone pharmacophore which is in bioisosteric relationship with the 1,3-diketoacid moiety of the ADK. Thus, it was of our interest to test the antiviral activity of the quercetin derivatives with an arylmethyl group attached. In this study, we prepared a series of the 7-O-arylmethylquercetin derivatives with various aromatic substituents and evaluated their antiviral activity against the SARS-associated coronavirus (SARS-CoV, SCV) as well as hepatitis C virus (HCV). Single difference in the aromatic substituent fine-tuned the biological activity of the 7-O-arylmethylquercetin derivatives to result in two different classes of derivatives selectively active against SCV and HCV.
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Amoros, M., Simös, C. M. O., Girre, L., Sauvager, F., and Cormier, M., Synergistic effect of flavones and flavonols against herpes simplex virus type 1 in cell culture. Comparison with the antiviral activity of propolis. J. Nat. Prod., 55, 1732–1740 (1992).
Ferry, D. R., Smith, A., Malkhandi, J., Fyfe, D. W., de Takats, P. G., Anderson, D., Baker, J., and Kerr, D. J., Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer Res., 2, 659–668 (1996).
Gozdek, A., Zhukov, I., Polkowska, A., Poznanski, J., Stankiewicz-Drogon, A., Pawlowicz, J. M., Zagorski-Ostoja, W., Borowski, P., and Boguszewska-Chachulska, A., NS3 Peptide, a novel potent hepatitis C virus NS3 helicase inhibitor: Its mechanism of action and antiviral activity in the replicon system. Antimicrob. Agents Chemother., 52, 393–401 (2008).
Harada, S., Haneda, E., Maekawa, T., Morikawa, Y., Funayama, S., Nagata, N., and Ohtsuki, K., Casein kinase II (CK-II)-mediated stimulation of HIV-1 reverse transcriptase activity and characterization of selective inhibitors in vitro. Biol. Pharm. Bull., 22, 1122–1126 (1999).
Kaul, T. N., Middleton, E., Jr., and Ogra, P. L., Antiviral effect of flavonoids on human viruses. J. Med. Virol., 15, 71–79 (1985).
Kim, J., Kim, K.-S., Lee, H. S., Park, K.-S., Park, S. Y., Kang, S.-Y., Lee, S. J., Park, H. S., Kim, D.-E., and Chong, Y., Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues. Bioorg. Med. Chem. Lett., 18, 4661–4665 (2008).
Lamson, D. W. and Brignall, M. S., Antioxidant and cancer III: quercetin. Altern. Med. Rev., 5, 196–208 (2000).
Lee, C., Lee, J. M., Lee, N.-R., Kim, D.-E., Jeong, Y.-J., and Chong, Y., Investigation of the pharmacophore space of severe acute respiratory syndrome coronavirus (SARSCoV) NTPase/helicase by dihydroxychromone derivatives. Bioorg. Med. Chem. Lett., 19, 4538–4541 (2009a).
Lee, C., Lee, J. M., Lee, N.-R., Jin, B.-S., Jang, K. J., Kim, D.-E., Jeong, Y.-J., and Chong, Y., Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase. Bioorg. Med. Chem. Lett., 19, 1636–1638 (2009b).
Lee, H. S., Park, K.-S., Lee, C., Lee, B., Kim, D.-E., and Chong, Y., 7-O-Arylmethylgalangin as a novel scaffold for anti-HCV agents. Bioorg. Med. Chem. Lett., 20, 5709–5712 (2010).
Li, M., Han, X., and Yu, B., Facile synthesis of flavonoid 7-Oglycosides. J. Org. Chem., 68, 6842–6845 (2003).
Lohmann, V., Korner, F., Koch, J., Herian, U., Theilmann, L., and Bartenschlager, R., Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science, 285, 110–113 (1999).
Sabui, S. K. and Venkateswaran, R. V., Synthesis of O-methyl epi-heliannuol E. Tetrahedron, 59, 8375–8381 (2003).
Vrijsen, R., Everaert, L., and Boeyé, A., Antiviral activity of flavones and potentiation by ascorbate. J. Gen. Virol., 69, 1749–1751 (1988).
Vroljk, J. M., Kaul, A., Hansen, B. E., Lohmann, V., Haagmans, B. L., Schalm, S. W., and Bartenschlager, R., A repliconbased bioassay for the measurement of interferons in patients with chronic hepatitis C. J. Virol. Methods, 110, 201–209 (2003).
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Park, H.R., Yoon, H., Kim, M.K. et al. Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV). Arch. Pharm. Res. 35, 77–85 (2012). https://doi.org/10.1007/s12272-012-0108-9
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DOI: https://doi.org/10.1007/s12272-012-0108-9