1991 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	03151040
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、陸上性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。本年度は、先に見出している抗腫瘍物質カリクリン類の絶対構造を明らかにするとともに、抗腫瘍物質スウィンホリド類の構造活性相関、プロティンフォスファタ-ゼ阻害剤オカダ酸および細胞融合阻害物質ハレナキノ-ルサルフェ-トの作用機作の検討を行った。さらに、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、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、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、新規抗腫瘍性物質の探索を行った。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性物質[海綿類‥‥ポリケチド(テオペデリン類),テルペノイド(ステリフェリン類,イルシノリド類,マノアリド類),ペプチド(オ-ビクラミドA),色素配糖体(アラウラント類):軟体動物‥‥ジテルペン類,糖タンパク,レクチン:海洋微生物‥‥マクロリド(アンフィジノリド類)]などを見出している。今後、顕著な活性を示す抗腫瘍性質物については、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

(26 results)

All Other

All Publications (26 results)

[Publications] I.Kitagawa: "Biologically Active Tridecapeptide Lactones from the Okinawan Marine Sponge Theonella swinhoei (Theonellidae).Structure of Theonellapeptolide Id." Tetrahedron. 47. 2169-2180 (1991)
[Publications] M.Doi: "Molecular conformation of Swintholide A,a Potent Cytotoxic Dimeric Macrolide from the Okinawan Marine Sponge Theonella swinhoei:X-ray Crystal Structure of Its Diketone Derivative" J.Org.Chem.,. 56. 3629-3632 (1991)
[Publications] M.Kobayashi: "The structures of Sarasinosides A1,A2,A3,B1,B2,B3,C1,C2,and C3,Nine New Norlanstane-Triterpenoidal Oligoglycosides from the Palauan Marine Sponge Asteropus sarasinosum" Chem.Pharm.Bull.,. 39. 2867-2877 (1991)
[Publications] S.Matsunaga: "Absolute Stereochemistry of the Calyculins,Potent Inhibitors of Protein Phosphatase 1 and 2A" Tetrahedron Lett.,. 32. 5605-5606 (1991)
[Publications] N.Fusetani: "Orbiculamide A:a Novel Cytotoxic Cyclic Peptide from a Marine Sponge Theonella sp." J.Am.Chem.Soc.,. 113. 7811-7812 (1991)
[Publications] N.Fusetani: "Cytotoxic Metabolites of the Marine sponge Mycale adhaerens Lambe." J.Org.Chem.,. 56. 4971-4974 (1991)
[Publications] A.Carl: "Reguration of Ca-Activated K^+ Channels by Protein Kinase A and Phosphatase Inhibitors" Am.J.Physiol.(Cell Physiol.30). 261. C387-C392 (1991)
[Publications] S.M.Wards: "Inhibition of Electrical Slow Waves and Ca^<2+> Currents of Gastric and Colonic Smooth Muscle by Phosphatase Inhibitors" Am.J.Physiol.(Cell Physiol.30). 261. C64-C70 (1991)
[Publications] R.Higuchi: "Glycosphingolipids from the Starfish Asterias pectinifera,2.Structure of three Ganglioside Molecular Species and a Homogeneous Ganglioside,and Biological Activity of the Ganglioside" Liebigs Ann.Chem.,. 1991. 1-10 (1991)
[Publications] R.Higuchi: "Glycosphingolipids from the Starfish Asterias amurensis versicolor Sladen,1.Isolation and Structure of Six New Cerebrosides,Asteriacerebrosides A-F,and Two Known Cerebrosides,Asterocerebroside A and Acanthacerebroside C" Liebigs Ann.Chem.,. 1991. 745-752 (1991)
[Publications] S.Sugiyama: "Stereochemistry of the Four Diastereomers of Ceramide and Ceramide Lactoside" Liebigs Ann.Chem.,. 1991. 349-356 (1991)
[Publications] M.Tsuda: "Stelloferins A-F,New Antineoplastic Isomalabaricane Triterpenes from the Okinawan Marine Sponge Jaspis stellifera" Tetrahedron. 47. 2181-2194 (1991)
[Publications] 0.Murata: "Eudistomidins E and F,New β-Carboline Alkaloids from the Okinawan Marine Tunicate Eudistoma glaucus" Tetrahedron Lett.,. 32. 3539-3542 (1991)
[Publications] J.Kobayashi: "Amphidinolides G and H:New Potent Antineoplastic Macrolides from the Cultured Symbiotic Dinoflagellate Amphidinium sp" J.Org.Chem.,. 56. 5221-5224 (1991)
[Publications] J.Kobayashi: "Amphidinolide F,A New Cytotoxic Macrolide from the Marine Dinoflagellate Amphidinium sp" J.Antibiot.,. 44. 1259-1261 (1991)
[Publications] I.Ohtani: "A New Aspect of an Advanced Mosher's Method.Absolute Configuration of Marine Triterpene Sipholenol-A" J.Org.Chem.,. 56. 1296-1298 (1991)
[Publications] M.O.Ishitsuka: "Isolation of a Monomeric Counterpart of the Marine Biscembranonoids,a Biogenetic Diels-Alder Precursor" Tetrahedron Lett.,. 32. 2917-2918 (1991)
[Publications] K.Iguchi: "Stereostructures of Unique 13-Membered Carbocyclic Cembranolides from the Soft Coral Lobophytum pauciflorum" Chem.Lett.,. 1991. 319-322 (1991)
[Publications] K.Muramoto: "The Amino-acid Sequence of Multiple Lectins of the Acorn Barnacle Megabalanus rosa and its Homology with Animal Lectins" Biochem.Biophys.Acta,. 1039. 42-51 (1991)
[Publications] K.Muramoto: "The Position of the Disulfide Bonds and the Glycosylation Site in a Lectin of the Acorn Barnacle Megabalanus rosa" Biochem.Biophys.Acta,. 1039. 52-60 (1991)
[Publications] M.Yamazaki: "Bacteriastatic and Cytolytic Activity of Purple Fluid from the Sea Hare" Develop.Comp.Immunol.,. 14. 379-383 (1991)
[Publications] S.Ikegami: "Immunological Survey of Planktonic Embryos and Larvae of the Starfish Asterina pectinifera obtained from the Sea Using a Monoclonal Antibody Directed Against Egg Polypeptides" Biol.Bull.,. 181. 95-103 (1991)
[Publications] S.Ikegami: "Achrosomal Division of Early Starfish Embryos Cultured in the Presence of Actinomycin D" Dev.Growth Differ.,. 33. 193-200 (1991)
[Publications] S.Ikegami: "Effect of Okadaic Acid on Embryonic Development of the Starfish,Asterina pectinifera" Biosci.Biotech.Biochem.(1991)
[Publications] 北川勲: "海洋生物を起源とする制癌剤の探索" 有機合成化学協会誌, 9 (1991)
[Publications] D.Uemura: "Bioactive Polyethers" Marine Bioorganic Chemistry,Vol 4 P.J.Scheuer ed.,Springer-Verlag, 31 (1991)

1991 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] I.Kitagawa: "Biologically Active Tridecapeptide Lactones from the Okinawan Marine Sponge Theonella swinhoei (Theonellidae).Structure of Theonellapeptolide Id." Tetrahedron. 47. 2169-2180 (1991)

[Publications] M.Doi: "Molecular conformation of Swintholide A,a Potent Cytotoxic Dimeric Macrolide from the Okinawan Marine Sponge Theonella swinhoei:X-ray Crystal Structure of Its Diketone Derivative" J.Org.Chem.,. 56. 3629-3632 (1991)

[Publications] M.Kobayashi: "The structures of Sarasinosides A1,A2,A3,B1,B2,B3,C1,C2,and C3,Nine New Norlanstane-Triterpenoidal Oligoglycosides from the Palauan Marine Sponge Asteropus sarasinosum" Chem.Pharm.Bull.,. 39. 2867-2877 (1991)

[Publications] S.Matsunaga: "Absolute Stereochemistry of the Calyculins,Potent Inhibitors of Protein Phosphatase 1 and 2A" Tetrahedron Lett.,. 32. 5605-5606 (1991)

[Publications] N.Fusetani: "Orbiculamide A:a Novel Cytotoxic Cyclic Peptide from a Marine Sponge Theonella sp." J.Am.Chem.Soc.,. 113. 7811-7812 (1991)

[Publications] N.Fusetani: "Cytotoxic Metabolites of the Marine sponge Mycale adhaerens Lambe." J.Org.Chem.,. 56. 4971-4974 (1991)

[Publications] A.Carl: "Reguration of Ca-Activated K^+ Channels by Protein Kinase A and Phosphatase Inhibitors" Am.J.Physiol.(Cell Physiol.30). 261. C387-C392 (1991)

[Publications] S.M.Wards: "Inhibition of Electrical Slow Waves and Ca^<2+> Currents of Gastric and Colonic Smooth Muscle by Phosphatase Inhibitors" Am.J.Physiol.(Cell Physiol.30). 261. C64-C70 (1991)

[Publications] R.Higuchi: "Glycosphingolipids from the Starfish Asterias pectinifera,2.Structure of three Ganglioside Molecular Species and a Homogeneous Ganglioside,and Biological Activity of the Ganglioside" Liebigs Ann.Chem.,. 1991. 1-10 (1991)

[Publications] R.Higuchi: "Glycosphingolipids from the Starfish Asterias amurensis versicolor Sladen,1.Isolation and Structure of Six New Cerebrosides,Asteriacerebrosides A-F,and Two Known Cerebrosides,Asterocerebroside A and Acanthacerebroside C" Liebigs Ann.Chem.,. 1991. 745-752 (1991)

[Publications] S.Sugiyama: "Stereochemistry of the Four Diastereomers of Ceramide and Ceramide Lactoside" Liebigs Ann.Chem.,. 1991. 349-356 (1991)

[Publications] M.Tsuda: "Stelloferins A-F,New Antineoplastic Isomalabaricane Triterpenes from the Okinawan Marine Sponge Jaspis stellifera" Tetrahedron. 47. 2181-2194 (1991)

[Publications] 0.Murata: "Eudistomidins E and F,New β-Carboline Alkaloids from the Okinawan Marine Tunicate Eudistoma glaucus" Tetrahedron Lett.,. 32. 3539-3542 (1991)

[Publications] J.Kobayashi: "Amphidinolides G and H:New Potent Antineoplastic Macrolides from the Cultured Symbiotic Dinoflagellate Amphidinium sp" J.Org.Chem.,. 56. 5221-5224 (1991)

[Publications] J.Kobayashi: "Amphidinolide F,A New Cytotoxic Macrolide from the Marine Dinoflagellate Amphidinium sp" J.Antibiot.,. 44. 1259-1261 (1991)

[Publications] I.Ohtani: "A New Aspect of an Advanced Mosher's Method.Absolute Configuration of Marine Triterpene Sipholenol-A" J.Org.Chem.,. 56. 1296-1298 (1991)

[Publications] M.O.Ishitsuka: "Isolation of a Monomeric Counterpart of the Marine Biscembranonoids,a Biogenetic Diels-Alder Precursor" Tetrahedron Lett.,. 32. 2917-2918 (1991)

[Publications] K.Iguchi: "Stereostructures of Unique 13-Membered Carbocyclic Cembranolides from the Soft Coral Lobophytum pauciflorum" Chem.Lett.,. 1991. 319-322 (1991)

[Publications] K.Muramoto: "The Amino-acid Sequence of Multiple Lectins of the Acorn Barnacle Megabalanus rosa and its Homology with Animal Lectins" Biochem.Biophys.Acta,. 1039. 42-51 (1991)

[Publications] K.Muramoto: "The Position of the Disulfide Bonds and the Glycosylation Site in a Lectin of the Acorn Barnacle Megabalanus rosa" Biochem.Biophys.Acta,. 1039. 52-60 (1991)

[Publications] M.Yamazaki: "Bacteriastatic and Cytolytic Activity of Purple Fluid from the Sea Hare" Develop.Comp.Immunol.,. 14. 379-383 (1991)

[Publications] S.Ikegami: "Immunological Survey of Planktonic Embryos and Larvae of the Starfish Asterina pectinifera obtained from the Sea Using a Monoclonal Antibody Directed Against Egg Polypeptides" Biol.Bull.,. 181. 95-103 (1991)

[Publications] S.Ikegami: "Achrosomal Division of Early Starfish Embryos Cultured in the Presence of Actinomycin D" Dev.Growth Differ.,. 33. 193-200 (1991)

[Publications] S.Ikegami: "Effect of Okadaic Acid on Embryonic Development of the Starfish,Asterina pectinifera" Biosci.Biotech.Biochem.(1991)

[Publications] 北川 勲: "海洋生物を起源とする制癌剤の探索" 有機合成化学協会誌, 9 (1991)

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

北川勲大阪大学, 薬学部, 教授 (20028830)

[Publications] 北川勲: "海洋生物を起源とする制癌剤の探索" 有機合成化学協会誌, 9 (1991)