• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of New Anticancer Agents with New Pharmacological Mechanism

Research Project

Project/Area Number 11672118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

MIKAMI Yoshihiro  Tokyo University of Pharmacy and Life Science School of Pharmacy, Associate professor, 薬学部, 助教授 (90229790)

Co-Investigator(Kenkyū-buntansha) KURODA Minpei  Tokyo University of Pharmacy and Life Stience School of Pharmacy, Instructor, 薬学部, 助手 (80266890)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsOSW-1 / steroidal glycoside / steroidal saponin / HL-60 cells / cytotoxic activity / antitumor activity / structure-activity relationship / anticancer agent / Ornithogalum thyrsoides / Galtonia candicans / candicanoside A / パネルスクリーニング / galtonioside A / 細胞増殖抑制活性
Research Abstract

Previously, we have found that an acylated cholestane glycoside (XDSW-1) isolated from the bulbs of Ornithogalum saundersiae showed potent cytotoxic and cytostatic activities against various human malignant tumor cells. In a continuation, we evaluated cytotoxic activity of OSW-1 derivatives against HL-60 human leukemia cells and revealed the structure-activity relationships. The cytotoxicity of steroidal saponins were also examined. The results are as follows.
1) A total of 24 OSW-1 derivatives, 19 of which were isolated from the bulbs of O. saundersiae, O. thyrsoides, and Galtonia candicans, and 5 of which were chemically synthesized, were evaluated for their cytotoxic activity against HL-60 cells, leading to the new findings of the structure-activity relationships of the OSW-1 related compounds. The role of the acylated diglycoside group attached at C-16 of the aglycon for the appearance of the potent cytotoxicity has not been revealed, and we consider that the assignment of the role … More would finally lead the development of a new anticancer agent with new pharmacological mechanism.
2) Two new cholestane glycosides, named galtonioside A (1) and candicanosoide A (2), were isolated from G, candicans and their structures were formulated by spectroscopic and chemical methods. Compounds 1 and 2 showed strong cytotoxic activity against HL-60 cells, which was as potent as the clinically applied anticancer agents, etoposide and methotrexate. In the Jpn. Fdn. for Cancer Res. 38 cell line assay, 1 and 2 displayed differential cytotoxicities, with breast cancer, CNS cancer, and lung cancer subpanel cell lines showing particular sensitivity but with colon cancer, ovarian cancer, and stomach cancer subpanel cell lines being relatively resistant to them. The pattern of differential cytotoxicity of 1 and 2 was evaluated by Compare Program and was revealed not to be correlated with that shown by any of the other compounds including currently used anticancer drugs (correlation coefficient value is about 0.5). This indicates that 1 and 2 may have a unique mode of action and the potentiality as the leads of new anticancer agents.
3) The cytotoxic activities of the steroidal saponins mainly isolated from the Liliaceae plants against HL-60 cells were examined. Some steroidal saponins evaluated showed considerable cytotoxic activities, which were almost as potent as that of etoposide used as a positive control. The activities were found to be sensitive to the monosaccharides constituting the sugar moieties and their sequences, as well as to the structures of the aglycons. " Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kuroda Minpei: "Galtonioside A, a novel cytotoxic cholestane glycoside from Galtonia candicans"Tetrahedron Lett.. 41. 251-255 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mimaki Yoshihiro: "Candicanoside A, a novel cytotoxic rearranged cholestane glycoside from Galtonia candicans"Helv. Chim. Acta. 83. 2698-2707 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Shigenori: "Cytotoxic activity of steroidal saponins against human oral tumor cell lines"Anticancer Res.. 20. 4189-4194 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mimaki Yoshihiro: "Flavonol glycosides and steroidal saponins from the leaves of Cestrum nocturnum and their cytotoxicity"J. Nat. Prod.. 64. 17-22 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda Minpei: "Cytotoxic cholestane glycosides from the bulbs of Ornithogalum saundersiae"J. Nat. Prod.. 64. 88-91 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda Minpei: "Steroidal glycosides from the bulbs of Camassia leichdinii and their cytotoxic activities"Chem. Pharm. Bull.. 49. 726-731 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Shigenori: "Cytotoxic activity of saponins from Camassia leichtlinii against human oral tumor cell lines"Anticancer Res.. 21. 959-964 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda Minpei: "Cholestane glycosides from the bulbs of Gahonia candicans and their cytotoxicity"Chem. Pharm. Bull.. 49. 1042-1046 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mimaki Yoshihiro: "Cytotoxic activities and structure-cytotoxic relationships of steroidal saponins"Biol. Pharm. Bull.. 24. 1286-1289 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda Minpei: "Galtonioside A, a novel cytotoxic cholestane glycoside from Galtonia candicans"Tetrahedron Lett. 41(2). 251-255 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mimaki Yoshihiro: "Candicanoside A, a novel cytotoxic rearranged cholestane glycoside from Galtonia candicans."Helv.Chim.Acra. 83(10). 2698-2707 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Shigenori: "Cytotoxic activity of steroidal saponins against human oral tumor cell lines."Anticancer Res. 20(6B). 4189-4194 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mimaki Yoshihiro: "Flavonol glycosides and steroidal saponins from the leaves of Cestrum nocturnum and their cytotoxicity."J.Nat.Prod. 64(1). 17-22 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda Minpei: "Cytotoxic cholestane glycosides from the bulbs of Ornithogalum sa undersiae."J.Nat.Prod. 64(2). 88-91 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda Minpei: "Steroidal glycosides from the bulbs of Camassia leichtlinii and their cytotoxic activities."Chem.Pham.Bull. 49(6). 726-731 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Furuya Shigenori: "Cytotoxic activity of saponins from Camassia leichtlinii against human oral tumor cell lines."Anticancer Res. 21(2A). 959-964 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuroda Minpei: "Cholestane glycosides from the bulbs of Galtonia candicans and their cytotoxicity."Chem.Pham.Bull. 49(8). 1042-1046 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mimaki Yoshihiro: "Cytotoxic activities and structure-cytotoxic relationships of steroidal saponins."Biol.Pharm.Bull. 24(11). 1286-1289 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Mimaki, K. Watanabe, Y. Ando, et al.: "Flavonol Glycosides and Steroidal Saponins from the Leaves of Cestrum nocturnum and Their Cytotoxicity"J. Nat. Prod.. 64・1. 17-22 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M. Kuroda, Y. Mimaki, A. Yokosuka, et al.: "Cytotoxic Cholestane Glycosides from the Bulbs of Ornithogalum saundersiae"J. Nat. Prod.. 64・1. 88-91 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S. Furuya, F. Takayama, Y. Mimaki, et al.: "Cytotoxic Activity of Saponins from Camassia leichtlinii against Human Oral Tumor Cell Lines"Anticancer Res.. 21・2A. 959-964 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M. Kuroda, Y. Mimaki, A. Yokosuka, et al.: "Cholestane Glycosides from the Bulbs of Galtonia candicans and Their Cytotoxicity"Chem. Pharm. Bull.. 49・8. 1042-1046 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y. Mimaki, A. Yokosuka, M. Kuroda, et al.: "Cytotoxic Activities and Structure-Cytotoxic Relationships of Steroidal Saponins"Biol. Pharm. Bull.. 24・11. 1286-1289 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshihiro Mimaki,Minpei Kuroda, et al.: "Candicanoside A, A Novel Cytotoxic Rearranged Cholestane Glycoside from Galtonia candicans"Helv.Chim.Acta. 83・10. 2698-2704 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 1999-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi