Skip to main content

Advertisement

SpringerLink
Log in

Structural modification on rupestonic acid leads to highly potent inhibitors against influenza virus

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

Influenza viruses are responsible for seasonal epidemics and occasional pandemics, which cause significant morbidity and mortality. Although several drugs (adamantanes and neuraminidase inhibitors) are available in the market, the worldwide spread of drug-resistant influenza strains poses an urgent need for novel antiviral drugs. Artemisia rupestris L. is a folk medicine used to treat cold. In this paper, we structurally modified rupestonic acid, a bioactive component of A. rupestris, to synthesize a series of 2-substituted rupestonic acid methyl esters (3a–3o). Their structures were fully characterized by 1H NMR, 13C NMR, HRMS spectra. Among them, compounds 3b and 3c exhibited potent activities against influenza H1N1 with micromolar IC50 values and might serve as new lead compounds for the treatment of influenza.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1

Similar content being viewed by others

References

  1. Abdiryim I, Halmurat (2001) An electron paramagnetic resonance study on the antioxidant effects of artemisia flavonoids. Chin Pharmacol Bull 17(6):648–650

    CAS  Google Scholar 

  2. Sirafil A, Ilhamjan X, Halmurat (2001) Regulation of p53, Fas and bcl-2 gene expressions with artemisia flavonoid in human hepatoma. Chin J Biochem Mol Biol 17(2):226–229. https://doi.org/10.13865/j.cnki.cjbmb.2001.02.020

    Article  CAS  Google Scholar 

  3. Fang MZ, Chao QF, Lan Y, Liu XN, Xin XU, Fan YH (2011) Antibacterial effect of the extract from Artemisia rupestris L. Food Sci Technol 36(1):160–166. https://doi.org/10.13684/j.cnki.spkj.2011.01.071

    Article  Google Scholar 

  4. Yin J, Ma L, Wang H, Yan H, Hu J, Jiang W, Li Y (2017) Chinese herbal medicine compound Yi-Zhi-Hao pellet inhibits replication of influenza virus infection through activation of heme oxygenase-1. Acta Pharm Sin B 7(6):630–637. https://doi.org/10.1016/j.apsb.2017.05.006

    Article  PubMed  PubMed Central  Google Scholar 

  5. Su Z, Wu H, Yang Y, Aisa HA, Slukhan U, Aripova S (2008) Preparative isolation of guaipyridine sesquiterpene alkaloid from Artemisia rupestris L. flowers using high-speed counter-current chromatography. J Sep Sci 31(12):2161–2166. https://doi.org/10.1002/jssc.200700683

    Article  CAS  PubMed  Google Scholar 

  6. Zhao Y, Su Z, Aisa HA (2009) 2-Phenoxychromone flavonoid glycoside from Artemisia rupestris. Chem Nat Compd 45(1):24–26. https://doi.org/10.1007/s10600-009-9218-0

  7. Xu GS, Chen XY, Yu DQ (1988) Rupestonic acid, a new sesquiterpene from Artemisia rupestris L. Acta Pharmacol Sin 23(2):122–125

    CAS  Google Scholar 

  8. Xu GS, Zhao W, Wu D, Yu DQ, He CH, Yang JJ, Sun F (1991) The structure and absolute configuration of isorupestonic acid from Artemisia rupestris L. Acta Pharmacol Sin 26(7):505–509

    CAS  Google Scholar 

  9. Li G, Zhao J-Y, Niu C, Nie L-F, Dong C-Z, Aisa HA (2017) Structure–activity relationship studies of 1-(1′-hydroxyalkyl)rupestonic acid methyl esters against influenza viruses. Bioorg Med Chem Lett 27(6):1484–1487. https://doi.org/10.1016/j.bmcl.2016.06.011

    Article  CAS  PubMed  Google Scholar 

  10. Yong J, Aisa HA (2011) Chemical modification of rupestonic acid and preliminarily in vitro antiviral activity against influenza A3 and B viruses. Bull Korean Chem Soc 32(4):1293–1297. https://doi.org/10.5012/bkcs.2011.32.4.1293

    Article  CAS  Google Scholar 

  11. Zhao J, Aisa HA (2012) Synthesis and anti-influenza activity of aminoalkyl rupestonates. Bioorg Med Chem Lett 22(6):2321–2325. https://doi.org/10.1016/j.bmcl.2012.01.056

    Article  CAS  PubMed  Google Scholar 

  12. Zhao J, Aisa HA (2012) Synthesis of novel isoxazole contained rupestonic acid derivatives and in vitro inhibitory activity against influenza viruses A and B. Chin J Org Chem 32:333–337. https://doi.org/10.6023/cjoc1108081

    Article  CAS  Google Scholar 

  13. Yong J, Lu C, Aisa HA (2013) Advances in studies on the rupestonic acid derivatives as anti-influenza agents. Mini Rev Med Chem 13(2):310–315. https://doi.org/10.2174/138955713804805229

    Article  CAS  PubMed  Google Scholar 

  14. He Y-W, Dong C-Z, Zhao J-Y, Ma L-L, Li Y-H, Aisa HA (2014) 1,2,3-Triazole-containing derivatives of rupestonic acid: click-chemical synthesis and antiviral activities against influenza viruses. Eur J Med Chem 76:245–255. https://doi.org/10.1016/j.ejmech.2014.02.029

    Article  CAS  PubMed  Google Scholar 

  15. Zhao J, Niu C, Li G, Aisa HA (2017) Synthesis of rupestonic acid derivatives with antiviral activity. Chem Nat Compd 53(2):276–283. https://doi.org/10.1007/s10600-017-1970-y

    Article  CAS  Google Scholar 

  16. Ma L-L, Wang H-Q, Wu P, Hu J, Yin J-Q, Wu S, Ge M, Sun W-F, Zhao J-Y, Aisa HA, Li Y-H, Jiang J-D (2016) Rupestonic acid derivative YZH-106 suppresses influenza virus replication by activation of heme oxygenase-1-mediated interferon response. Free Radical Bio Med 96:347–361. https://doi.org/10.1016/j.freeradbiomed.2016.04.021

    Article  CAS  Google Scholar 

  17. Smith W, Andrewes CH, Laidlaw PP (1933) A virus obtained from influenza patients. Lancet 222(5732):66–68. https://doi.org/10.1016/S0140-6736(00)78541-2

    Article  Google Scholar 

  18. Francis T (1940) A new type of virus from epidemic influenza. Science 92(2392):405–408. https://doi.org/10.1126/science.92.2392.405

    Article  PubMed  Google Scholar 

  19. Coleman M, Dowdle W, Pereira H, Schild G, Chang WK (1968) The Hong Kong/68 influenza A2 variant. Lancet 292(7583):1384–1386. https://doi.org/10.1016/S0140-6736(68)92683-4

    Article  Google Scholar 

  20. Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, Rahardjo AP, Puthavathana P, Buranathai C, Nguyen TD, Estoepangestie AT, Chaisingh A, Auewarakul P, Long HT, Hanh NT, Webby RJ, Poon LL, Chen H, Shortridge KF, Yuen KY, Webster RG, Peiris JS (2004) Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430(6996):209–213. https://doi.org/10.1038/nature02746

    Article  CAS  PubMed  Google Scholar 

  21. Morens DM, Fauci AS (2007) The 1918 influenza pandemic: insights for the 21st century. J Infect Dis 195(7):1018–1028. https://doi.org/10.1086/511989

    Article  PubMed  Google Scholar 

  22. Tafalla M, Buijssen M, Geets R, Vonk Noordegraaf-Schouten M (2016) A comprehensive review of the epidemiology and disease burden of Influenza B in 9 European countries. Hum Vaccin Immunother 12(4):993–1002. https://doi.org/10.1080/21645515.2015.1111494

    Article  PubMed  PubMed Central  Google Scholar 

  23. Davies WL, Grunert RR, Haff RF, McGahen JW, Neumayer EM, Paulshock M, Watts JC, Wood TR, Hermann EC, Hoffmann CE (1964) Antiviral activity of 1-adamantanamine (amantadine). Science 144(3620):862–863. https://doi.org/10.1126/science.144.3620.862

    Article  CAS  PubMed  Google Scholar 

  24. von Itzstein M, Wu W-Y, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, Colman PM, Varghese JN, Ryan DM, Woods JM, Bethell RC, Hotham VJ, Cameron JM, Penn CR (1993) Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 363:418. https://doi.org/10.1038/363418a0

    Article  Google Scholar 

  25. Babu YS, Chand P, Bantia S, Kotian P, Dehghani A, El-Kattan Y, Lin T-H, Hutchison TL, Elliott AJ, Parker CD, Ananth SL, Horn LL, Laver GW, Montgomery JA (2000) BCX-1812 (RWJ-270201): discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design. J Med Chem 43(19):3482–3486. https://doi.org/10.1021/jm0002679

    Article  CAS  PubMed  Google Scholar 

  26. Davies BE (2010) Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations. J Antimicrob Chemoth 65(2):ii5–ii10. https://doi.org/10.1093/jac/dkq015

    Article  CAS  Google Scholar 

  27. Wang H, Xu R, Shi Y, Si L, Jiao P, Fan Z, Han X, Wu X, Zhou X, Yu F, Zhang Y, Zhang L, Zhang L, Zhou D, Xiao S (2016) Design, synthesis and biological evaluation of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors. Eur J Med Chem 110:376–388. https://doi.org/10.1016/j.ejmech.2016.01.005

    Article  CAS  PubMed  Google Scholar 

  28. Grundy J, James BG, Pattenden G (1972) Esterification of sterically hindered carboxylic acids using dimethyl sulphate. Tetrahedron Lett 13(9):757–758. https://doi.org/10.1016/S0040-4039(01)84430-0

    Article  Google Scholar 

Download references

Acknowledgements

This work was financially supported by National Natural Science Foundation of China (Nos. 81402808, U1603101), 12th Chinese Recruitment Program of Global Experts (Thousand Talents Program) and Youth Innovation Promotion Association (No. 2015354). We would like to thank the members of Institute of Medicinal Biotechnology, Academy of Medical Sciences and Peking Union Medical College, for testing the anti-influenza activity of the synthesized compounds.

Author information

Authors and Affiliations

  1. Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, People’s Republic of China

    Mamateli Obul, Xincheng Wang, Jiangyu Zhao, Gen Li, Haji Akber Aisa & Guozheng Huang

  2. University of Chinese Academy of Sciences, Yuquan Rd 19 A, Beijing, 100049, People’s Republic of China

    Mamateli Obul & Xincheng Wang

Authors
  1. Mamateli Obul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xincheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiangyu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haji Akber Aisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guozheng Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Haji Akber Aisa or Guozheng Huang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Obul, M., Wang, X., Zhao, J. et al. Structural modification on rupestonic acid leads to highly potent inhibitors against influenza virus. Mol Divers 23, 1–9 (2019). https://doi.org/10.1007/s11030-018-9840-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-018-9840-5

Keywords

Search

Navigation