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Chemical Investigation of Antimalarial Compounds from Marine Organisms

Research Project

Project/Area Number 11672107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionUniversity of the Ryukyus

Principal Investigator

HIGA Tatsuo  University of the Ryukyus, college of Science Professor, 理学部, 教授 (10101461)

Co-Investigator(Kenkyū-buntansha) TANAKA Junichi  University of the Ryukyus, College of Science Associate Professor, 理学部, 助教授 (20163529)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsAntimalarial drugs / Marine Natural Products / Manzamines / マンザミンA / マラリア / 海綿
Research Abstract

Malaria is one of the most important infectious diseases. It is estimated to inflict more than 300 million people and to kill some two million people a year in the world. Chemotherapy is still the most effective method of treatment of the disease. However, because of the emergence of resistant parasites against the most frequently used drugs such as chloroquine, it is necessary to develop new effective and safe drugs. In this project we have screened in collaboration with Dr. A.U.Kara more than 100 compounds isolated from marine organisms. The screening was an in vivo test using mice infected with the rodent malaria parasite Plasmodiun berghei. Drugs of the doses ranging from 50 to 1000 μM/kg were injected to the mice on day 2 of postinfection and recorded the days and numbers of surviving mice. As a result manzamine A, a complex alkaloid from a sponge, was shown to be most effective antimalarial. Efficacy of manzamine A was compared with artemisinin and chloroquine. Manzamine A at a single dose of 100 μM/kg gave the best result with 40% recovery, survival of two out of five mice for 60 days postinfection. Artemisinin gave 20% recovery at a dose of 1000 μM/kg, while the treatment with chloroquine gave no recovery, all mice died by day 10. In order to examine structure activity relationship of the manzamine alkaloids, we have prepared Several derivatives of manzamine A.They were similarly tested together with 8-hydroxymanzamine A and manzamine F which have also been isolated from sponges. Only 8-hydroxymanzamine A showed some efficacy, but all others were not active. The result suggested that the complex framework of manzamine A would be important for the activity. Further work is needed to clarify the structure activity relationship and mechanism of the action of manzamine A.

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] K.K.H.Ang et al.: "In Vivo Antimalarial Activity of the Beta-Carboline Alkaloid Manzamine A"Antimicrob.Agents Chemother.. 44. 1645-1649 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kuniyoshi, et al.: "3-Bromobarekoxide, an Unusual Diterpene from Laurencia luzonensis."Chem.Commun.. 1155-1156 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.C.Roy, et al.: "New Cyclic Peptides from the Indonesian Sponge Theonella swinhoei"Tetrahedron. 56. 9079-9092 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Musri et al.: "New Sesquiterpene Carbonimidic Dichlorides and Related Compounds from the Sponge Stylotella aurantium"J.Nat.Prod.. 64. 111-113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Musri et al.: "Hipposulfates A and B, New Sesteriterpene Sulfates from an Okinawan Sponge Hippospongia ct. metachromia"J.Nat.Prod.. 64. 350-352 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Higa & M.Kuniyoshi: "Toxins Associated with Medicinal and Edible Seaweeds"J.Toxicol.-Toxin Reviews. 19. 119-137 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Higa et al.: "A.T.Tu & W.Gaffield (Eds.), Natural and Selected Synthetic Toxins, Biological Implications,"American Chemical Society, Washington, DC. 426 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Higa, I.I.Ohtani, and J.Tanaka: "Cytotoxins and Other Bioactive Compounds from Coral Reef Organisms. In A.T.Tu and W.Gaffield (Eds.), "Natural and Selected Synthetic Toxins, Biological Implications, ""American Chemical Society, Washington, DC. 12-21 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.K.H.Ang, M.J.Holmes, T.Higa, M.T.Hamann, and U.A.K.Kara: "In Vivo Antimalarial Activity of the Beta-Carboline Alkaloid Manzamine A."Antimicrob.Agents Chemother.. 44. 1645-1649 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kuniyoshi, M.S.Marma, T.Higa, G.Bernadinelli, and C.W.Jefford: "3-Bromobarekoxide, an Unusual Diterpene from Laurencia luzonensis."Chem.Commun.. 1155-1156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.C.Roy, I.I.Ohtani, T.Ichiba, J.Tanaka, R.Satari, and T.Higa: "New Cyclic Peptides from the Indonesian Sponge Theonella swinhoei."Tetrahedron. 56. 9079-9092 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Musri, J.Tanaka, and T.Higa: "New Sesquiterpene Carbonimidic Dichlorides and Related Compounds from the Sponge Stylotella aurantium."J.Nat.Prod.. 64. 111-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Musri, I.I.Ohtani, D.Nagaoka, J.Tanaka, and T.Higa: "Hipposulfates A and B, New Sesteriterpene Sulfates from an Okinawan Sponge Hippospongia ct.metachromia."J.Nat.Prod.. 64. 350-352 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] I Erdogan, J.Tanaka, T.Higa, and B.Sener: "Terpenoids from Two Species of the Aegean Sea."Nat.Prod.Sci.. 5. 177-180 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Higa and M.Kuniyoshi: "Toxins Associated with Medicinal and Edible Seaweeds."J.Toxicol.-Toxin Reviews. 19. 119-137 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.K.H.Ang: "In vivo antimalarial activity of the betacarboline alkaloid manzamine A"Antimicrob.Agents Chemother.. 44・6. 1645-1649 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kuniyoshi: "3-Bromobarekoxide, an unusual diterpene from Luarencia luzonensis"Chem.Commun.. 1155-1156 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.C.Roy: "New cyclic peptides from the Indonesian sponqe Theonella swinhoei"Tetrahedron. 56・46. 9079-9092 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Musman: "New sesquiterpene carbonimidic dichlorides and related compounds from the sponge"J.Nat.Prod.. 64・1. 111-113 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Higa,I.I.Ohtani,J.Tanaka: "Natural and Selected Syuthetic Tatins(ACS Symposium Ser.745)"American Chemical Society. 426 (2000)

    • Related Report
      1999 Annual Research Report

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

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