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Journal of Natural Medicines

, Volume 71, Issue 3, pp 506–512 | Cite as

Iriomoteolides-9a and 11a: two new odd-numbered macrolides from the marine dinoflagellate Amphidinium species

  • Keiko Kumagai
  • Masayuki Tsuda
  • Eri Fukushi
  • Jun Kawabata
  • Atsunori Masuda
  • Masashi TsudaEmail author
Original Paper

Abstract

Iriomoteolides-9a (1) and 11a (2), new 15- and 19-membered macrolides, respectively, have been isolated from the marine dinoflagellate Amphidinium species (strain KCA09052). Compounds 1 and 2 were obtained from the extracts of the algal cells inoculated in the PES and TKF seawater medium, respectively. The structures of 1 and 2 were assigned on the basis of detailed NMR analyses. Compounds 1 and 2 exhibited cytotoxic activity against human cervix adenocarcinoma HeLa cells.

Keywords

Macrolide Dinoflagellate Amphidinium Cytotoxic activity 

Notes

Acknowledgements

We thank S. Oka and A. Tokumitsu of the Equipment Management Center, Hokkaido University, for the ESIMS measurements. This study was partially supported by a Grants-in-Aid for Scientific Research (C) (no. 26670045 to M.T.) from the Japan Society for the Promotion of Science and the Kochi University President’s Discretionary Grant.

References

  1. 1.
    Kobayashi JI, Tsuda M (2004) Amphidinolides, bioactive macrolides from symbiotic marine dinoflagellates. Nat Prod Rep 21:77–93CrossRefPubMedGoogle Scholar
  2. 2.
    Kobayashi JI, Kubota T (2007) Bioactive macrolides and polyketides from marine dinoflagellates of the genus Amphidinium. J Nat Prod 70:451–460CrossRefPubMedGoogle Scholar
  3. 3.
    Kobayashi JI (2008) Amphidinolides and its related macrolides from marine dinoflagellates. J Antibiot 61:271–284CrossRefPubMedGoogle Scholar
  4. 4.
    Akakabe M, Kumagai K, Tsuda M, Konishi Y, Tominaga A, Kaneno D, Fukushi E, Kawabata J, Masuda A, Tsuda M (2016) Iriomoteolides-10a and 12a, cytotoxic macrolides from marine dinoflagellate Amphidinium species. Chem Pharm Bull 64:1019–1023CrossRefPubMedGoogle Scholar
  5. 5.
    Kumagai K, Tsuda M, Masuda A, Fukushi E, Kawabata J (2015) Iriomoteolide-2a, a cytotoxic 23-membered macrolide from marine benthic dinoflagellate Amphidinium species. Heterocycles 91:265–274CrossRefGoogle Scholar
  6. 6.
    Akakabe M, Kumagai K, Tsuda M, Konishi Y, Tominaga A, Tsuda M, Fukushi E, Kawabata J (2014) Iriomoteolide-13a, a cytotoxic 22-membered macrolide from a marine dinoflagellate Amphidinium species. Tetrahedron 70:2962–2965CrossRefGoogle Scholar
  7. 7.
    Kumagai K, Minamida M, Akakabe M, Tsuda M, Konishi Y, Tominaga A, Tsuda M, Fukushi E, Kawabata J (2015) Amphirionin-2, a novel linear polyketide with potent cytotoxic activity from a marine dinoflagellate Amphidinium species. Bioorg Med Chem Lett 25:635–638CrossRefPubMedGoogle Scholar
  8. 8.
    Minamida M, Kumagai K, Ulanova D, Akakabe M, Konishi Y, Tominaga A, Tanaka H, Tsuda M, Fukushi E, Kawabata J, Masuda A, Tsuda M (2014) Amphirionin-4 with potent proliferation-promoting activity on bone marrow stromal cells from a marine dinoflagellate Amphidinium species. Org Lett 16:4858–4861CrossRefPubMedGoogle Scholar
  9. 9.
    Akakabe M, Kumagai K, Tsuda M, Konishi Y, Tominaga A, Tsuda M, Fukushi E, Kawabata J (2014) Amphirionin-5, a novel linear polyketide from a cultured marine dinoflagellate Amphidinium species with a potent cell proliferation-promoting activity. Tetrahedron Lett 55:3491–3494CrossRefGoogle Scholar
  10. 10.
    Kobayashi J, Ishibashi M, Wälchli MR, Nakamura H, Hirata Y, Sasaki T, Ohizumi Y (1988) Amphidinolide C: the first twenty-five membered macrocyclic lactone with potent antineoplastic activity from the cultured dinoflagellate Amphidinium sp. J Am Chem Soc 110:490–494CrossRefGoogle Scholar
  11. 11.
    Kato M, Okauchi M, Nakagami S (2004) Development of a concentration technique for unicellular diatoms, Chaetoceros gracilis and Chaetoceros calcitrans, as food organisms. Suisanzoshoku 52:231–237Google Scholar
  12. 12.
    Ishibashi M, Takahashi M, Kobayashi JI (1995) Amphidinolides O and P, novel 15-membered macrolides from the dinoflagellate Amphidinium sp.: analysis of the relative stereochemistry and stable solution conformation. J Org Chem 60:6062–6066CrossRefGoogle Scholar
  13. 13.
    Williams DR, Myers BJ, Mi L (2000) Total synthesis of (−)-amphidinolide P. Org Lett 2:945–948CrossRefPubMedGoogle Scholar
  14. 14.
    Kobayashi J, Shigemori H, Ishibashi M, Yamasu T, Hirota H, Sasaki T (1991) Amphidinolides G and H: new potent cytotoxic macrolides from the cultured symbiotic dinoflagellate Amphidinium sp. J Org Chem 56:5221–5224CrossRefGoogle Scholar
  15. 15.
    Kobayashi JI, Shimbo K, Sato M, Shiro M, Tsuda M (2000) Absolute stereochemistry of amphidinolides G and H. Org Lett 2:2805–2807CrossRefPubMedGoogle Scholar
  16. 16.
    Usui T, Kazami S, Dohmae N, Mashimo Y, Kondo H, Tsuda M, Terasaki AG, Ohashi K, Kobayashi JI, Osada H (2004) Amphidinolide H, a potent cytotoxic macrolide, covalently binds on actin subdomain 4 and stabilizes actin filament. Chem Biol 11:1269–1277CrossRefPubMedGoogle Scholar
  17. 17.
    Kobayashi JI, Sato M, Ishibashi M (1993) Amphidinolide J: a cytotoxic macrolide from the marine dinoflagellate Amphidinium sp. Determination of the absolute stereochemistry. J Org Chem 58:2645–2646CrossRefGoogle Scholar
  18. 18.
    Ishibashi M, Takahashi M, Kobayashi JI (1997) Studies on the macrolides from marine dinoflagellate Amphidinium sp.: structures of amphidinolides R and S and a succinate feeding experiment. Tetrahedron 53:7827–7832CrossRefGoogle Scholar
  19. 19.
    Oguchi K, Tsuda M, Iwamoto R, Okamoto Y, Kobayashi JI, Fukushi E, Kawabata J, Ozawa T, Masuda A, Kitaya Y, Omasa K (2008) Iriomoteolide-3a, a cytotoxic 15-membered macrolide from a Marine Dinoflagellate Amphidinium species. J Org Chem 73:1567–1570CrossRefPubMedGoogle Scholar
  20. 20.
    Ishibashi M, Yamaguchi N, Sasaki T, Kobayashi JI (1994) Amphidinolide N, a novel 26-membered macrolide with remarkably potent cytotoxicity from the cultured marine dinoflagellate Amphidinium sp. J Chem Soc Chem Commun 12:1455–1456CrossRefGoogle Scholar
  21. 21.
    Takahashi Y, Kubota T, Imachi M, Wälchli MR, Kobayashi JI (2013) Revised structure and stereochemical assignments of amphidinolide N. J Anitibiot 66:277–279CrossRefGoogle Scholar
  22. 22.
    Bauer I, Maranda L, Young KA, Shimizu Y (1995) Isolation and structure of caribenolide I, a highly potent antitumor macrolide from a cultured free-swimming Caribbean dinoflagellate, Amphidinium sp. 51-36-5. J Org Chem 60:1084–1086CrossRefGoogle Scholar
  23. 23.
    Kobayashi J, Ishibashi M, Murayama T, Takamatsu M, Iwamura M, Ohizumi Y, Sasaki T (1990) Amphidinolide E, a novel antileukemic 19-membered macrolide from the cultured symbiotic dinoflagellate Amphidinium sp. J Org Chem 55:3421–3423CrossRefGoogle Scholar
  24. 24.
    Kubota T, Tsuda M, Kobayashi JI (2002) Absolute stereochemistry of amphidinolide E. J Org Chem 67:1651–1656CrossRefPubMedGoogle Scholar
  25. 25.
    Ishibashi M, Sato M, Kobayashi J (1993) Amphidinolide K, a new 19-membered macrolide from the cultured symbiotic dinoflagellate Amphidinium sp. J Org Chem 58:6928–6929CrossRefGoogle Scholar
  26. 26.
    Williams DR, Meyer KG (2001) Total synthesis of (+)-amphidinolide K. J Am Chem Soc 123:765–766CrossRefPubMedGoogle Scholar
  27. 27.
    Ko HM, Lee CW, Kwon HK, Chung HS, Choi SY, Chung YK, Lee E (2009) Total synthesis of (−)-amphidinolide K. Angew Chem Int Ed 48:2364–2366CrossRefGoogle Scholar
  28. 28.
    Tsuda M, Endo T, Kobayashi JI (2000) Amphidinolide T, novel 19-membered macrolide from marine dinoflagellate Amphidinium sp. J Org Chem 65:1349–1352CrossRefPubMedGoogle Scholar
  29. 29.
    Kobayashi JI, Kubota T, Endo T, Tsuda M (2001) Amphidinolides T2, T3, and T4, new 19-membered macrolides from the dinoflagellate Amphidinium sp. and the biosynthesis of amphidinolide T1. J Org Chem 66:134–142CrossRefPubMedGoogle Scholar
  30. 30.
    Kubota T, Endo T, Tsuda M, Shiro M, Kobayashi JI (2001) Amphidinolide T5, a new 19-membered macrolide from a dinoflagellate and X-ray structure of amphidinolide T1. Tetrahedron 57:6175–6179CrossRefGoogle Scholar
  31. 31.
    Tsuda M, Izui N, Shimbo K, Sato M, Fukushi E, Kawabata J, Katsumata K, Horiguchi T, Kobayashi JI (2003) Amphidinolide X, a novel 16-membered macrodiolide from dinoflagellate Amphidinium sp. J Org Chem 68:5339–5345CrossRefPubMedGoogle Scholar
  32. 32.
    Kubota T, Endo T, Takahashi Y, Tsuda M, Kobayashi JI (2006) Amphidinin B, a new polyketide metabolite from marine dinoflagellate Amphidinium sp. J Antibiot 59:512–516CrossRefPubMedGoogle Scholar
  33. 33.
    Keller MD, Selvin RC, Claus W, Guillard RRL (1987) Media for the culture of oceanic ultraphytoplankton. J Phycol 23:633–638CrossRefGoogle Scholar
  34. 34.
    Bauer I, Maranda L, Shimizu Y, Peterson RW, Cornell L, Steiner JR, Clardy J (1994) The structures of amphidinolide B isomers: strongly cytotoxic macrolides produced by a free-swimming dinoflagellate, Amphidinium sp. J Am Chem Soc 116:2657–2658CrossRefGoogle Scholar
  35. 35.
    Bauer I, Maranda L, Young KA, Shimizu Y, Huang S (1995) The isolation and structures of unusual 1, 4-polyketides from the dinoflagellate, Amphidinium sp. Tetrahedron Lett 36:991–994CrossRefGoogle Scholar
  36. 36.
    Huang SJ, Kuo CM, Lin YC, Chen YM, Lu CK (2009) Carteraol E, a potent polyhydroxyl ichthyotoxin from the dinoflagellate Amphidinium carterae. Tetrahedron Lett 50:2512–2515CrossRefGoogle Scholar
  37. 37.
    Meng Y, Van Wagoner RM, Misner I, Tomas C, Wright JLC (2010) Structure and biosynthesis of amphidinol 17, a hemolytic compound from Amphidinium carterae. J Nat Prod 73:409–415CrossRefPubMedGoogle Scholar
  38. 38.
    Nuzzo G, Cutignano A, Sardo A, Fontana A (2014) Antifungal amphidinol 18 and its 7-sulfate derivative from the marine dinoflagellate Amphidinium carterae. J Nat Prod 77:1524–1527CrossRefPubMedGoogle Scholar
  39. 39.
    Nakamura H, Kawase Y, Maruyama K, Murai A (1998) Studies on polyketide metabolites of a symbiotic dinoflagellate, Symbiodinium sp.: a new C30 marine alkaloid, zooxanthellamine, a plausible precursor for zoanthid alkaloids. Bull Chem Soc Jpn 71:781–787CrossRefGoogle Scholar
  40. 40.
    Horiguchi T, Yoshizawa-Ebata J, Nakayama T (2000) Halostylodinium arenarium, gen et sp. nov. (Dinophyceae), a coccoid sand-dwelling dinoflagellate from subtropical Japan. J Phycol 36:960–971CrossRefGoogle Scholar
  41. 41.
    Maranda L, Shimizu Y (1996) Amphidinium operculatum var. nov. gibbosum (Dinophyceae), a free-swimming marine species producing cytotoxic metabolites. J Phycol 32:873–879CrossRefGoogle Scholar
  42. 42.
    Murray S, Jørgensen MF, Daugbjerg N, Rhodes L (2004) Amphidinium revisited. II. Resolving species boundaries in the Amphidinium operculatum species complex (Dinophyceae), including the descriptions of Amphidinium trulla sp. nov. and Amphidinium gibbosum comb. nov. J Phycol 40:366–382CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2017

Authors and Affiliations

  • Keiko Kumagai
    • 1
  • Masayuki Tsuda
    • 1
  • Eri Fukushi
    • 2
  • Jun Kawabata
    • 2
  • Atsunori Masuda
    • 3
  • Masashi Tsuda
    • 4
    Email author
  1. 1.Science Research CenterKochi UniversityNankokuJapan
  2. 2.Research Faculty of AgricultureHokkaido UniversitySapporoJapan
  3. 3.College of AgricultureTamagawa UniversityMachidaJapan
  4. 4.Center for Advanced Marine Core Research and Department of Agriculture and Marine ScienceKochi UniversityNankokuJapan

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