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海洋生物を起源とする抗腫瘍性物質の探索と開発

Research Project

Project/Area Number 04151040
Research Category

Grant-in-Aid for Cancer Research

Allocation TypeSingle-year Grants
Research InstitutionOsaka University

Principal Investigator

北川 勲  大阪大学, 薬学部, 教授 (20028830)

Co-Investigator(Kenkyū-buntansha) 伏谷 伸宏  東京大学, 農学部, 教授 (70012010)
神谷 久男  北里大学, 水産学部, 教授 (80011964)
佐々木 琢磨  金沢大学, がん研究所, 教授 (90109976)
比嘉 辰雄  琉球大学, 理学部, 教授 (10101461)
池上 晋  広島大学, 生物生産学部, 教授 (80011980)
Project Period (FY) 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥18,500,000 (Direct Cost: ¥18,500,000)
Fiscal Year 1992: ¥18,500,000 (Direct Cost: ¥18,500,000)
Keywords海洋生物 / 抗腫瘍性物質 / 癌細胞増殖抑制 / 受精卵卵割阻害 / 海洋天然物質 / 癌化学療法 / 生物活性物質 / サンゴ礁生物
Research Abstract

海洋生物は特異な環境に生息し、適応するため、陸上生物とは異なる代謝系を発達させてきたと考えられる。したがって、それらの代謝産物の中には、陸上生物由来の天然物質にはみられない、新しい炭素骨格を有し、強力な抗腫瘍活性を示す癌化学療法剤開発につながるリード化合物の存在が期待される。
本研究では、沖縄サンゴ礁域、瀬戸内海、伊豆諸島をはじめ日本各地沿岸において採集した海綿類、八放サンゴ類、軟体動物など種々の海洋生物の試料について新規抗腫瘍活性物質の探索を行なった。抗腫瘍性物質の探索の予備スクリーニングとして、ウニおよびヒトデ受精卵卵割阻害効果や癌細胞増殖阻害効果をin vitroで迅速に検討している。また、プロテインホスファターゼ阻害剤オカダ酸の作用機作について詳しく検討するとともに、これまでに単離構造解明しin vitroで顕著な活性を示す抗腫瘍物質について、さらにin vivoでの活性を調べた。そして、今年度も、I.海綿類からポリエーテルマクロリド(オンナミド類,シリンドラミド,ミヤコリド,シナチロリド,アルトヒルチンA),アルカロイド(プチロミカリンA),ペプチド(テオスタチン類)など、II.八放サンゴ類からテルペノイド(ロバトリエノリド,カジナン型セスキテルペン),アルカロイド(ノルゾアンタミン類)など、III.軟体動物からジテルペン類.糖タンパク,アルカロイド(ピンナトキシン)など、多彩な化学構造を有する種々の新規抗腫瘍物質を見出だしている。今後、顕著な活性を示す抗腫瘍性物質については、さらに活性とその作用機序について詳細に調べるとともに、構造活性相関の観点から、化学修飾および化学合成を検討する。また。引き続いて海洋生物由来の新規抗腫瘍性物質の探索を継続する。

Report

(1 results)
  • 1992 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] M.Kobayashi: "Heterosigma-glycolipids I,II,III,and IV,four diacyl-glyceroglycolipids possessing w3-polyunsaturated fatty acid residues,from the raphidophycean dinoflagellate Heterosigma akashiwo" Chem.Pharm.Bull.,. 40. 1404-1410 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Kobayashi: "Two new 3-keto-4-methylene steroids,theonellasterone and conicasterone,and a Diels-Alder type dimeric steroid bistheonellasterone,from the Okinawan marine sponge Theonella swinhoei" Chem.Pharm.Bull.,. 40. 1773-1778 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Fusetane: "Theopederins A-E,potent antitumor metabolites from a marine sponge Theonella sp." J.Org.Chem.,. 57. 3828-3832 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Kanazawa: "Cylindramide:cytotoxic teteamic acid lactam from the marine sponge Halichondria cylindrata Tanita & Hoshino" Tetrahedron Lett.,. 34. 1065-1068 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Matsunaga: "Eight new cytotoxic metabolites closely related to onnamide A from to marine spoges of the genus Theonella" Tetrahedron. 48. 8369-8376 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Tanaka: "An antitumor substance ED-110,a derivative of BE-13793C" J.Antibiotics. 45. 1797-1798 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Suganuma: "Biochemical effects and tumor promotion of okadaic acid in glandular stomach of SD rats" Carcinogenesis. 13. 1841-1845 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Miyamoto: "Three new cytotoxic sesterterpenoids,inorlides A,B,and C form the nudibranch Chromodoris inornata" Tetrahedron Lett.,. 33. 5811-5814 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Miyamoto: "Structures of four new triterpenoid oligoglycosides:DS-penaustrosides A,B,C,and D from the sea cucumber Pentacta australis" J.Nat.Prod.,. 55. 940-946 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Higa: "Miyakolide:a bryostatin-like macrolide from a sponge,Polyfibrospongia sp" J.AM.Chem.Soc.,. 114. 7587-7588 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Sharma: "Two new diterpene isocyanides from a sponge of the family Adociae" Tetrahedron Lett.,. 33. 1593-1596 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Kusumi: "Elucidation of the relative and absilute configuration of lobatriene,a marine diterpene,by the modified Mosher's method" J.Org.Chem.,. 57. 1033-1035 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] I.Ohtani: "Structure and chemical properties of ptilomycalin A" J.Am.Chem.Soc.,. 114. 8472-8479 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] J.Kisugi: "A novel cytotoxic factor from a hermit crab,Clibanarius longitarsus" Chem.Pharm.Bull.,. 40. 1641-1643 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Muramoto: "The amino-acid sequence of a lectin from conger eel,Conger myriaster,skin mucus" Biochem.Biophys.Acta. 111. 129-136 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] J.Kobayashi: "Plakortenin,a new cytotoxic carboxylic acid from the Okinawan marine sponge Plakortis sp." Tetrathedron Lett.,. 33. 2579-2580 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Ishida: "Agelasine G,a new antileukemic alkaloid from the Okinawan marine sponge Agelas sp." Chem.Pharm.Bull.,. 40. 766-767 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Ikegami: "Effect of okadaic acid on embryonic development of the starfish,Asterina pectinifera" Biosci.Biotech.Biochem.,. 56. 1007-1011 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Ikegami: "Interaction of starfish embryonic cells with the complex of okadaic acid and monoclonal antibody specific to okadaic acid" Biosci.Biotech.Biochem.,. 56. 1666-1666 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Ikegami: "Selective inhibition of membrana fusion events in echinoderm gametes and embryos by halenaquinol sulfate" FEBS lett.,. 302. 284-286 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Toyota: "Construction of cyclopropa(3,4)pyrrolo(3,2-e)indol-4-one (CPI) unit of antitumor antibiotic CC-1065" J.Chem.Soc.,Perkin I. 1992. 547-552 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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