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Official Journal of the Japan Wood Research Society

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The polar neutral and basic taxoids isolated from needles and twigs of Taxus cuspidata and their biological activity

Journal of Wood Science volume 54, pages 390–401 (2008)Cite this article

Abstract

Twelve basic taxoids and 22 neutral taxoids were isolated from basic and polar neutral fractions of the extracts of needles and twigs of Taxus cuspidata. Among them, taxine NA-13, 3,11-cyclotaxinine NN-1, taxinine NN-6, 11(15→1)abeo-taxinine NN-1, taxine NA-8, and taxine NA-4 were isolated first from natural sources by us. The cytotoxic activity of isolated compounds was evaluated against three human cell lines: normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). 7-Epitaxol, 7-epicephalomannine, taxinine NN-6, taxine NA-2, taxuspine H, and taxagifine were active toward VA-13 cells and 7-epitaxol, 7-epicephalomannine, taxinine NN-1, 9,10-deacetyltaxinine, and taxagifine were active toward HepG2 cells. The multidrug-resistant (MDR) cancer reversal activity of isolated compounds was evaluated on the basis of the amount of vincristine (VCR) accumulated in MDR human ovarian cancer 2780 AD. Taxine NA-8, taxine NA-2, 5-cinnamoyl-10-acetyltaxicin II, and taxinine NN-1 indicated stronger MDR cancer reversal activity than verapamil. The result of primary screening based on 39 human cancer cell lines suggests that taxinine NN-1 belongs to a new mechanistic class and is a new anticancer agents. 7-Epicephalomannine was found to be an effective anticancer agent with tubulin as its molecular target, which is the same as paclitaxel.

References

  1. Kingston DGI, Molinero AA, Rimoldi JM (1993) The taxane diterpenoids. Prog Chem Org Nat Prod 61:1–192

    CAS  Google Scholar 

  2. Baloglu E, Kingston DGI (1999) The taxane diterpenoids. J Nat Prod 62:1448–1472

    Article  CAS  PubMed  Google Scholar 

  3. Kobayashi J, Ogiwara A, Hosoyama H, Sigemori H, Yoshida N, Sasaki T, Li Y, Iwasaki S, Naito M, Tsuruo T (1994) Taxuspines A∼C, new taxoids from Japanese yew Taxus cuspidata inhibiting drug transport activity of p-glycoprotein in multidrug-resistant cells. Tetrahedron 50:7401–7416

    Article  CAS  Google Scholar 

  4. Kobayashi J, Hosoyama H, Sigemori H, Koiso Y, Iwasaki S (1995) Taxuspine D, a new taxane diterpene from Taxus cuspidata with potent inhibitory activity against Ca2+-induced depolymerization of microtubules. Experimentia 51:592–595

    Article  CAS  Google Scholar 

  5. Kobayashi J, Inubushi A, Hosoyama H, Yoshida N, Sasaki T, Shigemori H (1995) Taxuspines E∼H and J, new taxoids from the Japanese yew Taxus cuspidata. Tetrahedron 51:5971–5978

    Article  CAS  Google Scholar 

  6. Ando M, Sakai J, Zhang S, Watanabe Y, Kosugi K, Suzuki T, Hagiwara H (1997) A new basic taxoid from Taxus cupidata. J Nat Prod 60:499–501

    Article  CAS  Google Scholar 

  7. Kosugi K, Sakai J, Zhang S, Watanabe Y, Sasaki H, Suzuki T, Hagiwara H, Hirose K, Ando M, Tomida A, Turuo T (2000) Neutral taxoids from Taxus cuspidata as modulators of multidrugresistant tumor cells. Phytochemistry 54:839–845

    Article  CAS  PubMed  Google Scholar 

  8. Sakai J, Sasaki H, Kosugi K, Zhang S, Hirata N, Hirose K, Tomida A, Turuo T (2001) Two taxoids from Taxus cuspidata as modulations of multidrug-resistant tumor cells. Heterocycles 54:999–1009

    Article  CAS  Google Scholar 

  9. Tachibana S, Ishikawa H, Itoh K (2005) Antifungal activities of compounds isolated from the leaves of Taxus cuspidata va. nana against pathogenic fungi. J Wood Sci 51:181–184

    Article  CAS  Google Scholar 

  10. Shiro M, Sato T, Koyama H, Maki Y, Nakanishi K, Uyeo S (1966) The stereochemistry of taxinine: X-ray analysis of 2,5,9,10-tetra-O-acetyl-14-bromotaxinol. J Chem Soc Chem Commun 97–98

  11. Dukes M, Eyre DH, Harrison JW, Lythgoe B (1965) The stereochemistry of taxicin-I and taxicin-II. Tetrahedron Lett 6:4765–4773

    Article  Google Scholar 

  12. Eyre DH, Harrison JW, Lythgoe B (1967) Taxine. Part VI. The stereochemistry of taxicin-I and taxicin-II. J Chem Soc C 452–462

  13. Yoshizaki F, Madarame M, Takahashi C, Hisamichi S (1986) Principal constituents of the seeds of Japanese yew (Taxus cuspidate). Shoyakugaku Zashi 40:429–432

    CAS  Google Scholar 

  14. Ando M (2000) Jpn. Appl JP 2000044523 A, 15 February 2000. JP 19980214507, 29 July 1998. Priority: JP 19980214507, 29 July 1998. Isolation of taxane diterpenoids from needle leaves of Taxus cuspidata. Chem Abstr 132:156816

    Google Scholar 

  15. Ando M (2001) PCT Int Appl WO 2001007040 A1, 1 February 2001. Appl WO 2000-JP 5036, 27 July 2000. Priority: JP 1999-214273, 28 July 1999; JP 1999-224652, 6 August 1999; JP 2000-76404, 14 March 2000. Multidrug-resistant cancer overcoming agents and process for producing the same. Chem Abstr 2001, 134:136666

    Google Scholar 

  16. Huang CHO, Kingston DGI, Magri NF, Samaranayake G (1986) New taxanes from taxus brevifolia. J Nat Prod 49:665–669

    Article  CAS  PubMed  Google Scholar 

  17. Chmurny GN, Hilton BD, Brobst S, Look SA, Witherup KM, Beutler JA (1992) 1H-and 13C-NMR assignments for taxol, 7-epi-taxol, and cephalomannine. J Nat Prod 55:414–423

    Article  CAS  PubMed  Google Scholar 

  18. Wani MC, Taylor HL, Wall ME (1972) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc19: 2325–2326

    Google Scholar 

  19. Bellis PD, Lovati M, Pace R, Pererlongo F, Zini GF (1995) Isolation of 7-epi-cephalomannine from Taxus × media cv. “Hicksii” needles. Fitoterapia 66:521–524

    Google Scholar 

  20. Shi Q, Wang HK, Bastow KF, Tachibana Y, Chen K, Lee FY, Lee KH (2001) Antitumor agents 210, synthesis and evaluation of taxoid-epipodophyllotoxin conjugates as novel cytotoxic agents. Bioorg Med Chem 9:2999–3004

    Article  CAS  PubMed  Google Scholar 

  21. Daniewski WM, Gumulka M, Anczwski W, Masnyk M, Bloszyk E, Gupta KK (1998) Why the yew tree (Taxus baccata) is not attacked by insects. Phytochemsitry 49:1279–1282

    Article  CAS  Google Scholar 

  22. Zhang H, Tadeda Y, Sun H (1995) Taxanes from Taxus yunnanesis. Phytochemistry 39:1147–1151

    Article  CAS  Google Scholar 

  23. Ettouati L, Ahond A, Convert O, Laurent D, Poupat C, Potier P (1988) Plantes de nouvelle-caledonie. 114. Taxanes isoles des feuilles d’Austrotaxus spicata Compton (taxacees). Bull Soc Chim Fr 4:749–755

    Google Scholar 

  24. Shi QW, Oritani T, Zhao D, Murakami R, Oritani T (2000) Three new taxoids from the seeds of Japanese yew, Taxus cuspidata. Planta Med 66:294–299

    Article  CAS  PubMed  Google Scholar 

  25. Zhang JZ, Fang QC, Liang XT, He CH, Kong M, He WY, Jin XL (1995) Taxoids from the barks of Taxus wallichiana. Phytochemistry 40:881–884

    Article  CAS  Google Scholar 

  26. Chen YJ, Chen CY, Shen YC (1999) New taxoids from the seeds of Taxus chinesis. J Nat Prod 62:149–151

    Article  CAS  PubMed  Google Scholar 

  27. Shigemori H, Wang XX, Yoshida N, Kobayashi J (1997) Taxuspines X-Z, new taxoids from Japanese yew Taxus cuspidate. Chem Pharm Bull 45:1205–1208

    Article  CAS  Google Scholar 

  28. Appendino G, Gariboldi P, Pisetta A, Bombardelli E, Gabetta B (1992) Taxanes from Taxus baccata. Phytochemistry 31:4253–4257

    Article  CAS  Google Scholar 

  29. Jenniskens LHD, van Rozendaal ELM, van Beek TA (1996) Identification of six taxine alkaloids from Taxus baccata needles. J Nat Prod 59:117–123

    Article  CAS  Google Scholar 

  30. Yue Q, Fang QC, Liang XT (1996) A taxane-11,12-oxide from Taxus yunnanensis. Phytochemistry 43:639–642

    Article  CAS  Google Scholar 

  31. Yang SJ, Fang JM, Cheng YA (1996) Taxanes from Taxus mairei. Phytochemistry 43:839–842

    Article  CAS  Google Scholar 

  32. Wang XX, Shigemori H, Kobayashi J (1998) Taxezopidines B-H, new taxoids from Japanese yew Taxus cuspidata. J Nat Prod 61:474–479

    Article  CAS  Google Scholar 

  33. Appendino G, Lusso P, Gariboldi P, Bombardelli E, Gabetta B (1992) A 3,11-cyclotaxane from Taxus baccata. Phytochemistry 31:4259–4262

    Article  CAS  Google Scholar 

  34. Kobayashi T, Kurono M, Sato H, Nakanishi K (1972) Nature of photochemically induced transannular hydrogen abstraction of taxinines. J Am Chem Soc 19:2863–2865

    Article  Google Scholar 

  35. Yoshizaki F, Fukuda M, Hisamichi S, Ishida T, In Y (1988) Structures of taxane diterpenoids from the seeds of Japanese yew, Taxus cuspidata. Chem Pharm Bull 36:2098–2102

    Article  CAS  Google Scholar 

  36. Zhang Z, Jia Z, Zhu Z, Cui Y, Cheng J, Wang Q (1990) New taxanes from Taxus chinensis. Planta Med 56:293–294

    Article  CAS  PubMed  Google Scholar 

  37. Chauviere G, Guenard D, Pascard C, Picot F, Potier P, Prange T (1982) Taxagifine: new taxane derivative from Taxus baccata L. (Taxaceae). J Chem Soc Chem Commun 495–496

  38. Chattopadhyay SK, Sharma RP (1995) A taxane from the Himalayan yew, Taxus wallichiana. Phytochemistry 39:935–936

    Article  CAS  Google Scholar 

  39. Kobayashi J, Hosoyama H, Wang XX, Shigemori H, Sudo Y, Tsuruo T (1998) Modulation of multidrug resistance by taxuspine C and other taxoids from Japanese yew. Bioorg Med Chem Lett 8:1555–1558

    Article  CAS  PubMed  Google Scholar 

  40. Chiang HC, Woods MC, Nakadaira Y, Nakanishi K (1967) The structures of four new taxinine congeners, and a photochemical transannular reaction. J Chem Soc Chem Commun 1201–1202

  41. Hosoyama H, Shigemori H, In Y, Ishida T, Kobayashi J (1998) Occurrence of a new dimeric compound of 5-oxotaxinine A through Diels-Alder cycloaddition. Tetrahedron Lett 39:2159–2162

    Article  CAS  Google Scholar 

  42. Kingston DGI, Hawkins DR, Ovington L (1982) New taxanes from Taxus brevifolia. J Nat Prod 45:466–470

    Article  CAS  PubMed  Google Scholar 

  43. Schneider B, Zhao Y, Blitzke T, Schmitt B, Nookandeh A, Sun X, Stockigt J (1998) Taxane analysis by high performance liquid chromatography-nuclear magnetic resonance spectroscopy of Taxus species. Phytochem Anal 9:237–244

    Article  CAS  Google Scholar 

  44. Shi QW, Oritani T, Kiyota H, Zhao D (2000) Taxane diterpenoids from Taxus yunnanensis and Taxus cuspidata. Phytochemistry 54:829–834

    Article  CAS  PubMed  Google Scholar 

  45. Suzuki H, Sako M, Hirota K (1998) Thermolysis of taxinine and taxinine H. Allylic rearrangement of the ester moiety in the C-ring. Chem Pharm Bull 46:1314–1316

    Article  CAS  Google Scholar 

  46. Bai J, Kitabatake M, Toyoizumi K, Fu L, Zhang S, Dai J, Sakai J, Hirose K, Yamori T, Tomida A, Tsuruo T, Ando M (2004) Production of biologically active taxoids by a callus culture of Taxus cuspidata. J Nat Prod 67:58–63

    Article  CAS  PubMed  Google Scholar 

  47. Ueda K, Cardarelli C, Gottesman MM, Pastan I (1987) Expression of a full-length cDNA for the human “MDR1” gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci USA 84:3004–3008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ueda K, Komano T (1988) The multidrug-resistance gene MDR1. Gan To Kagaku Ryoho 15:2858–2862

    CAS  PubMed  Google Scholar 

  49. Tsuruo T, Iida-Saito H, Kawabata H, Oh-hara T, Hamada H, Utakoji T (1986) Characteristics of resistance to adriamycin in human myelogenous leukemia K562 resistant to adriamycin and in isolated clones. Jpn J Cancer Res 77:682–692

    CAS  PubMed  Google Scholar 

  50. Shigemori H, Kobayashi J (2004) Biological activity and chemistry of taxoids from the Japanese yew, Taxus cuspidata. J Nat Prod 67:245–256

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. Liyan Wang

    Present address: Department of Pharmacy Engineering and Applied Chemistry, College of Chemistry and Chemistry Engineering, Qiqihar University, Qiqihar, Heilongjiang, 161006, People’s Republic of China

Authors and Affiliations

  1. Graduate School of Science and Technology, Niigata University, Niigata, 950-2181, Japan

    Liyan Wang, Liming Bai, Daisuke Tokunaga, Yusuke Watanabe, Toshiaki Hasegawa, Wanxia Tang & Yuhua Bai

  2. Department of Chemistry and Chemical Engineering, Niigata University, Niigata, 950-2181, Japan

    Jun-ichi Sakai

  3. KNC Laboratories Co. Ltd., Kobe, Hyogo, 651-2271, Japan

    Katsutoshi Hirose

  4. Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan

    Takao Yamori, Akihiro Tomida & Takashi Tsuruo

  5. 22-20 Keiwa-machi, Taihaku-ku, Sendai, 982-0823, Japan

    Masayoshi Ando

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  1. Liyan Wang
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Correspondence to Masayoshi Ando.

Additional information

Part of this work was presented at the 74th Annual Meeting of the Chemical Society of Japan, Tanabe, March 1998, and the 41st Symposium on the Chemistry of Terpenes, Essential Oils, and Aromatics, Gifu, December 1998. The results of this work were also presented as patent documents at PCT Int: Appl WO 2001007040 A1, February 2001; Appl WO 2000-Jp 5036, 27 July 2000. Priority: JP 1999-214273, 28 July 1999; JP 1999-224652, 6 August 1999; JP 2000-76404, 14 March 2000

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Wang, L., Bai, L., Tokunaga, D. et al. The polar neutral and basic taxoids isolated from needles and twigs of Taxus cuspidata and their biological activity. J Wood Sci 54, 390–401 (2008). https://doi.org/10.1007/s10086-008-0964-6

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  • DOI: https://doi.org/10.1007/s10086-008-0964-6

Key words

  • Taxus cuspidata
  • Taxoid
  • Cytotoxic activity
  • MDR-cancer reversal activity
  • Taxinine NN-1