1990 Fiscal Year Annual Research Report

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	02151037
Research Institution	Osaka 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) 古森徹哉九州大学, 薬学部, 教授 (80037572) 柿澤寛筑波大学, 化学系, 教授 (50015492)
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あるいは生態防御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、新しい骨格を持ち、強力な抗腫瘍活性を示す癌化学療法剤開発のリ-ド化合物の存在が期待される。本研究において、沖縄サンゴ礁域、瀬戸内海、伊豆半島をはじめ日本各地沿岸において採集した海綿類、ホヤ類、軟体動物、海洋微生物など種々の海洋生物の試料について新規抗腫瘍性物質の探索を行った。抗腫瘍活性物質の探索の予備スクリ-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。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。そして以下のように、多彩な化学構造を有する種々の新規抗腫瘍物質[<海綿類>___〜‥‥マクロリド(13ーデオキシテダノリド,スウィンホリド類),ステロイド配糖体(パチャストレロシドA),イソクマリン(ヒブリピラノン),アルカロイド(ニファテシン類,プチロミカリンB),ポリケチド(カリクリン類,スポンジアラクトン),アミノ酸関連(プレアリディンA):<ホヤ類>___〜‥‥マクロリド(イエジマリド類):<軟体動物>___〜‥‥ジテルペン類,糖タンパク:<海洋微生物>___〜‥‥マクロリド(アンフィジノリドE)]などを見出している。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。

Research Products

(23 results)

All Other

All Publications (23 results)

[Publications] M.Kobayashi: "The absolute stereostructure of swinholide A,a potent cytotoxic dimeric macrolide from the Okinawan marine sponge <Theonella>___ー <swinhoei>___ー." Chem.Pharm.Bull.,. 38. 2409-2418 (1990)
[Publications] M.Kobayashi: "Three cytotoxic dimeric macrolides,swinholides B,and C and isoswinholide A,congeners of swinholide A,from the Okinawan marine sponge <Theonella>___ー <swinhoei>___ー." Chem.Pharm.Bull.,. 38. 2960-2966 (1990)
[Publications] J.Tanaka: "The absolute stereostructure of misakinolide A,a potent cytotoxic dimeric macrolide from an Okinawan marine sponge <Theonella>___ー ^・sp." Chem.Pharm.Bull.,. 38. 2967-2970 (1990)
[Publications] S.Matsunaga: "Calyculins E,F,G,and H,additional inhibitors of protein phosphatases 1 and 2A,from the marine sponge <Discodermia>___ー <calyx>___ー." Tetrahedron. 46. (1990)
[Publications] H.Hirota: "Stellettamide A,an antifungal alkaloid from a marine sponge of the genus <Stelletta>___ー." Tetrahedron Lett.,. 31. 4163-4164 (1990)
[Publications] N.Fusetani: "Research toward “drugs from the sea"." New J.Chem.,. 14. 721-728 (1990)
[Publications] S.Nishiwaki: "Estimation of tumor promoting activity and structureーfunction relationship of okadaic acid derivatives." Carcinogenesis. 11. 1837-1841 (1990)
[Publications] D.Uemura: "Cytotoxic alkaloids from the marine sponges." J.Nat.Prod.,. 53. (1990)
[Publications] T.Miyamoto: "Isolation and structures of threetriterpenoid aglycones,cucumechinol A,B,and C,from the sea cucumber <Cucumaria>___ー <echinata>___ー." Liebigs Ann.Chem.,. 39-42 (1990)
[Publications] T.Miyamoto: "Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber <Cucumaria>___ー <echinata>___ー." Liebigs Ann.Chem.,. 453-460 (1990)
[Publications] J.Kobayashi: "Niphatesines AーD,novel antineoplastic pyridine alkaloids from the Okinawan marine sponge <Niphates>___ー sp." J.Chem.Soc.Perkin Trans I. 3301-3303 (1990)
[Publications] J.Kobayashi: "Amphidinolide E,a novel antileukemic 19ーmembered macrolide from the cultured symbiotic dinoflagellate <Amphidinium>___ー sp." J.Org.Chem.,. 55. 3421-3423 (1990)
[Publications] M.Ishibashi: "PurealidinーA,a new cytotoxic bromotyrosineーderived alkaloid from the Okinawan marine sponge <Psammaplysillapurea>___ー." Experientia. (1990)
[Publications] G.ーC.Zheng: "Cytotoxic hydroperoxylepidozenes from the actinia <Anthoplleura>___ー <pacifica>___ー Uchida." J.Org.Chem.,. 55. 3677-3679 (1990)
[Publications] T.Kusumi: "A novel chlorinated biscembranoide from the marine soft coral <Sarchophyton>___ー <glaucum>___ー." J.Org.Chem.,. 55. 6286-6289 (1990)
[Publications] M.O.Ishitsuka: "Microviridin,a novel tricyclic depsipeptide from the toxic cyanobacterium <Microcystis>___ー <viridis>___ー." J.Am.Chem.Soc.,. 112. 8180-8182 (1990)
[Publications] H.Kamiya: "Purification and characterization of antibacterial and antineoplastic protein secretion of a sea hare,<Aplysia>___ー <juliana>___ー." Toxicon. 27. 1269-1277 (1989)
[Publications] R.Goto: "Purification and characterization of an agglutinin of the soft coral <Sinularia>___ー sp." Develop.Comp.Immunol.,. (1991)
[Publications] Y.Kikuchi: "Iejimalides C and D,new antineoplastic 24ーmembered macrolide sulfates from the Okinawan marine tunicate <Eudistoma>___ー cf.<rigida>___ー." Tetrahedron Lett.,. 32. 797-798 (1991)
[Publications] J.Kobayashi: "Eudistomidins B,C,and D:Novel antileukemic alkaloids from the Okinawan marine tunicate <Eudistoma>___ー <glaucus>___ー." J.Org.Chem.,. 55. 3666-3670 (1990)
[Publications] H.Hirota: "Structure of a novel steroidal saponin,pachastrelloside A,obtained from a marine sponge of the genus <Pachastrella>___ー." Tetrahedron Lett.,. 31. 3321-3324 (1990)
[Publications] S.Ikegami: "Chromatin maturation during early development of the starfish,<Asterina>___ー <pectinifera>___ー." Adv.Invert.Reprod.,. 5. 75-80 (1990)
[Publications] D.Uemura: "Bioorganic Marine Chemistry,Vol.4 Bioactive polyethers." P.J.Scheuer ed.,SpringerーVerlag,Berlin Heidelberg, 31 (1991)

1990 Fiscal Year Annual Research Report

海洋生物を起源とする抗腫瘍性物質の探索と開発

Principal Investigator

北川勲大阪大学, 薬学部, 教授 (20028830)

Research Products

[Publications] M.Kobayashi: "The absolute stereostructure of swinholide A,a potent cytotoxic dimeric macrolide from the Okinawan marine sponge <Theonella>_ー <swinhoei>_ー." Chem.Pharm.Bull.,. 38. 2409-2418 (1990)

[Publications] M.Kobayashi: "Three cytotoxic dimeric macrolides,swinholides B,and C and isoswinholide A,congeners of swinholide A,from the Okinawan marine sponge <Theonella>_ー <swinhoei>_ー." Chem.Pharm.Bull.,. 38. 2960-2966 (1990)

[Publications] J.Tanaka: "The absolute stereostructure of misakinolide A,a potent cytotoxic dimeric macrolide from an Okinawan marine sponge <Theonella>___ー ^・sp." Chem.Pharm.Bull.,. 38. 2967-2970 (1990)

[Publications] S.Matsunaga: "Calyculins E,F,G,and H,additional inhibitors of protein phosphatases 1 and 2A,from the marine sponge <Discodermia>_ー <calyx>_ー." Tetrahedron. 46. (1990)

[Publications] H.Hirota: "Stellettamide A,an antifungal alkaloid from a marine sponge of the genus <Stelletta>___ー." Tetrahedron Lett.,. 31. 4163-4164 (1990)

[Publications] N.Fusetani: "Research toward “drugs from the sea"." New J.Chem.,. 14. 721-728 (1990)

[Publications] S.Nishiwaki: "Estimation of tumor promoting activity and structureーfunction relationship of okadaic acid derivatives." Carcinogenesis. 11. 1837-1841 (1990)

[Publications] D.Uemura: "Cytotoxic alkaloids from the marine sponges." J.Nat.Prod.,. 53. (1990)

[Publications] T.Miyamoto: "Isolation and structures of threetriterpenoid aglycones,cucumechinol A,B,and C,from the sea cucumber <Cucumaria>_ー <echinata>_ー." Liebigs Ann.Chem.,. 39-42 (1990)

[Publications] T.Miyamoto: "Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber <Cucumaria>_ー <echinata>_ー." Liebigs Ann.Chem.,. 453-460 (1990)

[Publications] J.Kobayashi: "Niphatesines AーD,novel antineoplastic pyridine alkaloids from the Okinawan marine sponge <Niphates>___ー sp." J.Chem.Soc.Perkin Trans I. 3301-3303 (1990)

[Publications] J.Kobayashi: "Amphidinolide E,a novel antileukemic 19ーmembered macrolide from the cultured symbiotic dinoflagellate <Amphidinium>___ー sp." J.Org.Chem.,. 55. 3421-3423 (1990)

[Publications] M.Ishibashi: "PurealidinーA,a new cytotoxic bromotyrosineーderived alkaloid from the Okinawan marine sponge <Psammaplysillapurea>___ー." Experientia. (1990)

[Publications] G.ーC.Zheng: "Cytotoxic hydroperoxylepidozenes from the actinia <Anthoplleura>_ー <pacifica>_ー Uchida." J.Org.Chem.,. 55. 3677-3679 (1990)

[Publications] T.Kusumi: "A novel chlorinated biscembranoide from the marine soft coral <Sarchophyton>_ー <glaucum>_ー." J.Org.Chem.,. 55. 6286-6289 (1990)

[Publications] M.O.Ishitsuka: "Microviridin,a novel tricyclic depsipeptide from the toxic cyanobacterium <Microcystis>_ー <viridis>_ー." J.Am.Chem.Soc.,. 112. 8180-8182 (1990)

[Publications] H.Kamiya: "Purification and characterization of antibacterial and antineoplastic protein secretion of a sea hare,<Aplysia>_ー <juliana>_ー." Toxicon. 27. 1269-1277 (1989)

[Publications] R.Goto: "Purification and characterization of an agglutinin of the soft coral <Sinularia>___ー sp." Develop.Comp.Immunol.,. (1991)

[Publications] Y.Kikuchi: "Iejimalides C and D,new antineoplastic 24ーmembered macrolide sulfates from the Okinawan marine tunicate <Eudistoma>_ー cf.<rigida>_ー." Tetrahedron Lett.,. 32. 797-798 (1991)

[Publications] J.Kobayashi: "Eudistomidins B,C,and D:Novel antileukemic alkaloids from the Okinawan marine tunicate <Eudistoma>_ー <glaucus>_ー." J.Org.Chem.,. 55. 3666-3670 (1990)

[Publications] H.Hirota: "Structure of a novel steroidal saponin,pachastrelloside A,obtained from a marine sponge of the genus <Pachastrella>___ー." Tetrahedron Lett.,. 31. 3321-3324 (1990)

[Publications] S.Ikegami: "Chromatin maturation during early development of the starfish,<Asterina>_ー <pectinifera>_ー." Adv.Invert.Reprod.,. 5. 75-80 (1990)

[Publications] D.Uemura: "Bioorganic Marine Chemistry,Vol.4 Bioactive polyethers." P.J.Scheuer ed.,SpringerーVerlag,Berlin Heidelberg, 31 (1991)

1990 Fiscal Year Annual Research Report

海洋生物を起源とする抗腫瘍性物質の探索と開発

Principal Investigator

北川 勲 大阪大学, 薬学部, 教授 (20028830)

Research Products

[Publications] M.Kobayashi: "The absolute stereostructure of swinholide A,a potent cytotoxic dimeric macrolide from the Okinawan marine sponge <Theonella>___ー <swinhoei>___ー." Chem.Pharm.Bull.,. 38. 2409-2418 (1990)

[Publications] M.Kobayashi: "Three cytotoxic dimeric macrolides,swinholides B,and C and isoswinholide A,congeners of swinholide A,from the Okinawan marine sponge <Theonella>___ー <swinhoei>___ー." Chem.Pharm.Bull.,. 38. 2960-2966 (1990)

[Publications] J.Tanaka: "The absolute stereostructure of misakinolide A,a potent cytotoxic dimeric macrolide from an Okinawan marine sponge <Theonella>___ー ^・sp." Chem.Pharm.Bull.,. 38. 2967-2970 (1990)

[Publications] S.Matsunaga: "Calyculins E,F,G,and H,additional inhibitors of protein phosphatases 1 and 2A,from the marine sponge <Discodermia>___ー <calyx>___ー." Tetrahedron. 46. (1990)

[Publications] H.Hirota: "Stellettamide A,an antifungal alkaloid from a marine sponge of the genus <Stelletta>___ー." Tetrahedron Lett.,. 31. 4163-4164 (1990)

[Publications] N.Fusetani: "Research toward “drugs from the sea"." New J.Chem.,. 14. 721-728 (1990)

[Publications] S.Nishiwaki: "Estimation of tumor promoting activity and structureーfunction relationship of okadaic acid derivatives." Carcinogenesis. 11. 1837-1841 (1990)

[Publications] D.Uemura: "Cytotoxic alkaloids from the marine sponges." J.Nat.Prod.,. 53. (1990)

[Publications] T.Miyamoto: "Isolation and structures of threetriterpenoid aglycones,cucumechinol A,B,and C,from the sea cucumber <Cucumaria>___ー <echinata>___ー." Liebigs Ann.Chem.,. 39-42 (1990)

[Publications] T.Miyamoto: "Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber <Cucumaria>___ー <echinata>___ー." Liebigs Ann.Chem.,. 453-460 (1990)

[Publications] J.Kobayashi: "Niphatesines AーD,novel antineoplastic pyridine alkaloids from the Okinawan marine sponge <Niphates>___ー sp." J.Chem.Soc.Perkin Trans I. 3301-3303 (1990)

[Publications] J.Kobayashi: "Amphidinolide E,a novel antileukemic 19ーmembered macrolide from the cultured symbiotic dinoflagellate <Amphidinium>___ー sp." J.Org.Chem.,. 55. 3421-3423 (1990)

[Publications] M.Ishibashi: "PurealidinーA,a new cytotoxic bromotyrosineーderived alkaloid from the Okinawan marine sponge <Psammaplysillapurea>___ー." Experientia. (1990)

[Publications] G.ーC.Zheng: "Cytotoxic hydroperoxylepidozenes from the actinia <Anthoplleura>___ー <pacifica>___ー Uchida." J.Org.Chem.,. 55. 3677-3679 (1990)

[Publications] T.Kusumi: "A novel chlorinated biscembranoide from the marine soft coral <Sarchophyton>___ー <glaucum>___ー." J.Org.Chem.,. 55. 6286-6289 (1990)

[Publications] M.O.Ishitsuka: "Microviridin,a novel tricyclic depsipeptide from the toxic cyanobacterium <Microcystis>___ー <viridis>___ー." J.Am.Chem.Soc.,. 112. 8180-8182 (1990)

[Publications] H.Kamiya: "Purification and characterization of antibacterial and antineoplastic protein secretion of a sea hare,<Aplysia>___ー <juliana>___ー." Toxicon. 27. 1269-1277 (1989)

[Publications] R.Goto: "Purification and characterization of an agglutinin of the soft coral <Sinularia>___ー sp." Develop.Comp.Immunol.,. (1991)

[Publications] Y.Kikuchi: "Iejimalides C and D,new antineoplastic 24ーmembered macrolide sulfates from the Okinawan marine tunicate <Eudistoma>___ー cf.<rigida>___ー." Tetrahedron Lett.,. 32. 797-798 (1991)

[Publications] J.Kobayashi: "Eudistomidins B,C,and D:Novel antileukemic alkaloids from the Okinawan marine tunicate <Eudistoma>___ー <glaucus>___ー." J.Org.Chem.,. 55. 3666-3670 (1990)

[Publications] H.Hirota: "Structure of a novel steroidal saponin,pachastrelloside A,obtained from a marine sponge of the genus <Pachastrella>___ー." Tetrahedron Lett.,. 31. 3321-3324 (1990)

[Publications] S.Ikegami: "Chromatin maturation during early development of the starfish,<Asterina>___ー <pectinifera>___ー." Adv.Invert.Reprod.,. 5. 75-80 (1990)

[Publications] D.Uemura: "Bioorganic Marine Chemistry,Vol.4 Bioactive polyethers." P.J.Scheuer ed.,SpringerーVerlag,Berlin Heidelberg, 31 (1991)

北川勲大阪大学, 薬学部, 教授 (20028830)

[Publications] M.Kobayashi: "The absolute stereostructure of swinholide A,a potent cytotoxic dimeric macrolide from the Okinawan marine sponge <Theonella>_ー <swinhoei>_ー." Chem.Pharm.Bull.,. 38. 2409-2418 (1990)

[Publications] M.Kobayashi: "Three cytotoxic dimeric macrolides,swinholides B,and C and isoswinholide A,congeners of swinholide A,from the Okinawan marine sponge <Theonella>_ー <swinhoei>_ー." Chem.Pharm.Bull.,. 38. 2960-2966 (1990)

[Publications] S.Matsunaga: "Calyculins E,F,G,and H,additional inhibitors of protein phosphatases 1 and 2A,from the marine sponge <Discodermia>_ー <calyx>_ー." Tetrahedron. 46. (1990)

[Publications] T.Miyamoto: "Isolation and structures of threetriterpenoid aglycones,cucumechinol A,B,and C,from the sea cucumber <Cucumaria>_ー <echinata>_ー." Liebigs Ann.Chem.,. 39-42 (1990)

[Publications] T.Miyamoto: "Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber <Cucumaria>_ー <echinata>_ー." Liebigs Ann.Chem.,. 453-460 (1990)

[Publications] G.ーC.Zheng: "Cytotoxic hydroperoxylepidozenes from the actinia <Anthoplleura>_ー <pacifica>_ー Uchida." J.Org.Chem.,. 55. 3677-3679 (1990)

[Publications] T.Kusumi: "A novel chlorinated biscembranoide from the marine soft coral <Sarchophyton>_ー <glaucum>_ー." J.Org.Chem.,. 55. 6286-6289 (1990)

[Publications] M.O.Ishitsuka: "Microviridin,a novel tricyclic depsipeptide from the toxic cyanobacterium <Microcystis>_ー <viridis>_ー." J.Am.Chem.Soc.,. 112. 8180-8182 (1990)

[Publications] H.Kamiya: "Purification and characterization of antibacterial and antineoplastic protein secretion of a sea hare,<Aplysia>_ー <juliana>_ー." Toxicon. 27. 1269-1277 (1989)

[Publications] Y.Kikuchi: "Iejimalides C and D,new antineoplastic 24ーmembered macrolide sulfates from the Okinawan marine tunicate <Eudistoma>_ー cf.<rigida>_ー." Tetrahedron Lett.,. 32. 797-798 (1991)

[Publications] J.Kobayashi: "Eudistomidins B,C,and D:Novel antileukemic alkaloids from the Okinawan marine tunicate <Eudistoma>_ー <glaucus>_ー." J.Org.Chem.,. 55. 3666-3670 (1990)

[Publications] S.Ikegami: "Chromatin maturation during early development of the starfish,<Asterina>_ー <pectinifera>_ー." Adv.Invert.Reprod.,. 5. 75-80 (1990)