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1996 Fiscal Year Final Research Report Summary

Search for new compounds to overcome multidrug resistance from natural sources

Research Project

Project/Area Number 06558089
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field Bioorganic chemistry
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KOBAYASHI Junichi  Hokkaido Univ., Fac.Pharm.Sci., Professor, 薬学部, 教授 (90221241)

Co-Investigator(Kenkyū-buntansha) SHIGEMORI Hideyuki  Hokkaido Univ., Fac.Pharm.Sci., Assistant Professor, 薬学部, 助手 (70202108)
Project Period (FY) 1994 – 1996
KeywordsMDR modifier / Japanese yew / multidrug-resistance / P-glycoprotein / antitumor / tubulin
Research Abstract

In this research project, we investigated on search for new compounds to overcome multidrug resistance (MDR) from natural sources.
From the Japanese yew Taxus cuspidata Sieb.et Zucc.collected at Sapporo, 22 new taxoids and related diterpenoids, taxuspines A-H and J-W,were isolated and the structures elucidated on the basis of spectroscopic data and chemical means. Taxuspines B,C,and J increased accumulation of vincristine in multidrug-resistant cells, while taxol did not show such activity. These new taxoids exhibited no cytotoxicity and were not toxic for mice in vivo. These results suggest that some taxoids may become useful lead compounds to overcome multidrug resistance in tumor cells. On the other hand, taxuspine D markedly inhibited Ca^<2+>-induced depolymerization of microtubules and the potency corresponded to half to one third of that of taxol, although taxuspine D lacks both the oxetane ring and N-acylphenylisoserine moiety which are associated with this unique activity in taxol. Taxuspine E,having the oxetane ring but not containing the N-acylphenylisoserine moiety, exhibited potent cytotoxicity against KB tumor cells. More powerful and specific MDR modifiers may be found through further studies of structure-activity relationship on the new compounds obtained in this study.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] J. Kobayashi: "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 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J. Kobayashi: "Taxuspine D, a new taxane diterpene from Japanese yew Taxus cuspidata" Experientia. 51. 592-595 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J. Kobayashi: "Taxuspines E〜H and J, new taxoids from the Japanese yew Taxus cuspidata" Tetrahedron. 51. 5971-5978 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] X. -x. Wang: "Taxuspines K, L, and M, new taxoids from Japanese yew Taxus cuspidata" Tetrahedron. 52. 2337-2342 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J. Kobayashi: "Taxuspines N, O, and P, new taxoids from Japanese yew Taxus cuspidata" Tetrahedron. 52. 5391-5396 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Hosoyama: "Taxuspines U, V, and W, new taxane and related diterpenoids from the Japanese yew Taxus cuspidata" Tetrahedron. 52. 13145-13150 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Kobayashi: "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 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Kobayashi: "Taxuspines D,a new taxane diterpene from Japanese yew Taxus cuspidata" Experientia. 51. 592-595 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Kobayashi: "Taxuspines E-H and J,new taxoids from Taxus cuspidata with potent inhibitory activity against Ca^<2+>-induced depolymerization of microtubules" Tetrahedron. 51. 5971-5978 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] X.-x.Wang: "Taxuspines K,L,and M,new taxoids from Japanese yew Taxus cuspidata" Tetrahedron. 52. 2337-2342 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Kobayashi: "Taxuspines N,O,and P,new taxoids from Japanese yew Taxus cuspidata" Tetrahedron. 52. 5391-5396 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Hosoyama: "Taxuspines U,V,and W,new taxane and related diterpenoids from the Japanese yew Taxus cuspidata" Tetrahedron. 52. 13145-13150 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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