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Euphorins A–H: bioactive diterpenoids from Euphorbia fischeriana

  • Original Paper
  • Biologically Active Natural Products from Microorganisms and Plants
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Abstract

Phytochemical investigation of the roots of Euphorbia fischeriana resulted in the isolation of 23 diterpenoids (123), which were classified into five subtypes, namely, ent-rosane (19), ent-abietane (1016), ent-kaurane (17), ingenane (1822), and lathyrane (23). The chemical structures of eight new compounds, namely, euphorin A (4), B (5), C (7), D (9), E (13), F (14), G (15), and H (16), were elucidated on the basis of extensive 1D and 2D NMR spectroscopic analyses, as well as single crystal X-ray structure analysis. A number of compounds (2, 6, 7, 10, 11, 13, 16, 19, 20, 22, and 23) showed inhibitory activity on the formation of mammospheres in human breast cancer MCF-7 cells at a final concentration of 10 μM, suggesting the potential of these bioactive diterpenoids for further investigation of the action targeting cancer stem cells.

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References

  1. Asada Y, Sukemori A, Watanabe T, Malla KJ, Yoshikawa T, Li W, Koike K, Chen CH, Akiyama T, Qian K, Nakagawa-Goto K, Morris-Natschke SL, Lee KH (2011) Stelleralides A–C, novel potent anti-HIV daphnane-type diterpenoids from Stellera chamaejasme L. Org Lett 13:2904–2907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sasaki T, Li W, Zaike S, Asada Y, Li Q, Ma F, Zhang Q, Koike K (2013) Antioxidant lignoids from leaves of Ribes nigrum. Phytochemistry 95:333–340

    Article  CAS  PubMed  Google Scholar 

  3. Li D, Li W, Higai K, Koike K (2014) Protein tyrosine phosphatase 1B inhibitory activities of ursane- and lupane-type triterpenes from Sorbus pohuashanensis. J Nat Med 68:427–431

    Article  PubMed  Google Scholar 

  4. Sasaki T, Li W, Higai K, Koike K (2015) Canthinone alkaloids are novel protein tyrosine phosphatase 1B inhibitors. Bioorg Med Chem Lett 25:1979–1981

    Article  CAS  PubMed  Google Scholar 

  5. Kuang X, Li W, Kanno Y, Mochizuki M, Inouye Y, Koike K (2014) Cycloartane-type triterpenes from Euphorbia fischeriana stimulate human CYP3A4 promoter activity. Bioorg Med Chem Lett 24:5423–5427

    Article  CAS  PubMed  Google Scholar 

  6. Kuang X, Li W, Kanno Y, Yamashita N, Nemoto K, Asada Y, Koike K (2016) ent-Atisane diterpenoids from Euphorbia fischeriana inhibit mammosphere formation in MCF-7 cells. J Nat Med 70:120–126

    Article  CAS  PubMed  Google Scholar 

  7. Traditional Chinese Medicine Dictionary; Pergamon: Shanghai Scientific and Technical Publishers, (1985) 4:5651–5653

  8. Shi QW, Su XH, Kiyota H (2008) Chemical and pharmacological research of the plants in genus Euphorbia. Chem Rev 108:4295–4327

    Article  CAS  PubMed  Google Scholar 

  9. Vasas A, Hohmann J (2014) Euphorbia diterpenes: isolation, structure, biological activity, and synthesis (2008–2012). Chem Rev 114:8579–8612

    Article  CAS  PubMed  Google Scholar 

  10. Wang HB, Wang XY, Liu LP, Qin GW, Kang TG (2015) Tigliane diterpenoids from the Euphorbiaceae and Thymelaeaceae families. Chem Rev 115:2975–3011

    Article  CAS  PubMed  Google Scholar 

  11. Butler MS, Robertson AA, Cooper MA (2014) Natural product and natural product derived drugs in clinical trials. Nat Prod Rep 31:1612–1661

    Article  CAS  PubMed  Google Scholar 

  12. Sun YX, Liu JC (2011) Chemical constituents and biological activities of Euphorbia fischeriana Steud. Chem Biodivers 8:1205–1214

    Article  CAS  PubMed  Google Scholar 

  13. Nagashima F, Sekiguchi T, Takaoka S, Asakawa Y (2004) Terpenoids and aromatic compounds from the New Zealand liverworts Plagiochila, Schistochila, and Heteroscyphus species. Chem Pharm Bull (Tokyo) 52:556–560

    Article  CAS  Google Scholar 

  14. Liu ZG, Li ZL, Bai J, Meng DL, Li N, Pei YH, Zhao F, Hua HM (2014) Anti-inflammatory diterpenoids from the roots of Euphorbia ebracteolata. J Nat Prod 77:792–799

    Article  CAS  PubMed  Google Scholar 

  15. Shi HM, Williams ID, Sung HH, Zhu HX, Ip NY, Min ZD (2005) Cytotoxic diterpenoids from the roots of Euphorbia ebracteolata. Planta Med 71:349–354

    Article  CAS  PubMed  Google Scholar 

  16. Pei Y, Koike K, Han B, Jia Z, Nikaido T (1999) Fischeria A, a novel norditerpene lactone from Euphorbia fischeriana. Tetrahedron Lett 40:951–952

    Article  CAS  Google Scholar 

  17. Uemura D, Hirata Y (1972) Two new diterpenoids, jolkinolides A and B, obtained from Euphorbia jolkini Boiss (Euphorbiaceae). Tetrahedron Lett 13:1387–1390

    Article  Google Scholar 

  18. Lal AR, Cambie RC, Rutledge PS, Woodgate PD (1990) Chemistry of Fijian plants. Part 6. ent-Pimarane and ent-abietane diterpenes from Euphorbia fidjiana. Phytochemistry 29:2239–2246

    Article  CAS  Google Scholar 

  19. Liu G, Müller R, Rüedi P (2003) Chemical transformations of phyllocladane (=13β-kaurane) diterpenoids. Helv Chim Acta 86:420–438

    Article  CAS  Google Scholar 

  20. Ding Y, Jia Z (1991) Tetracyclic diterpenols from Euphorbia sieboldiana. Phytochemistry 30:2413–2415

    Article  CAS  Google Scholar 

  21. Jia Z, Ding Y (1991) New Diterpenoids from Euphorbia sieboldiana. Planta Med 57:569–571

    Article  CAS  PubMed  Google Scholar 

  22. Sorg B, Hecker E (1982) On the chemistry of ingenol. II. Esters of ingenol and Δ7,8-isoingenol. Z Naturforsch B Chem Sci 37B:748–756

    CAS  Google Scholar 

  23. Uemura D, Nobuhara K, Nakayama Y, Shizuri Y, Hirata Y (1976) The structure of new lathyrane diterpenes, jolkinols A, B, C, and D, from Euphorbia jolkini Boiss. Tetrahedron Lett 17:4593–4596

    Article  Google Scholar 

  24. Clevers H (2011) The cancer stem cell: premises, promises and challenges. Nat Med 17:313–319

    Article  CAS  PubMed  Google Scholar 

  25. Greaves M (2011) Cancer stem cells renew their impact. Nat Med 17:1046–1048

    Article  CAS  PubMed  Google Scholar 

  26. Pattabiraman DR, Weinberg RA (2014) Tackling the cancer stem cells—what challenges do they pose? Nat Rev Drug Discov 13:497–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhao S, Kanno Y, Nakayama M, Makimura M, Ohara S, Inouye Y (2012) Activation of the aryl hydrocarbon receptor represses mammosphere formation in MCF-7 cells. Cancer Lett 317:192–198

    Article  CAS  PubMed  Google Scholar 

  28. Altmomare A, Burla MC, Camalli M, Cascarano M, Giacovazzo C, Guagliardi A, Polidori G (1994) SIR92—a program for automatic solution of crystal structure by direct method. J Appl Crystallogr 27:435

    Google Scholar 

  29. Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr A 64:112–122

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partially supported by JSPS KAKENHI Grant Numbers 25460136 and 26460133.

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Correspondence to Wei Li.

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Kuang, X., Li, W., Kanno, Y. et al. Euphorins A–H: bioactive diterpenoids from Euphorbia fischeriana . J Nat Med 70, 412–422 (2016). https://doi.org/10.1007/s11418-016-0987-z

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  • DOI: https://doi.org/10.1007/s11418-016-0987-z

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