1991 Fiscal Year Annual Research Report

新規構造を有する天然物由来抗癌物質に関する研究

Research Project

Project/Area Number	03151016
Research Institution	The University of Tokyo
Principal Investigator	瀬戸治男東京大学, 応用微生物研究所, 教授 (10013335)
Co-Investigator(Kenkyū-buntansha)	馬替純二東京工業大学, 生命理工学部, 講師 (60199643) 長田裕之理化学, 研究所, 研究員 (80160836) 柿沼勝巳東京工業大学, 理学部, 教授 (90092543) 長尾善光徳島大学, 薬学部, 教授 (40027074) 岩崎成夫東京大学, 応用微生物研究所, 教授 (00013326)
Keywords	セコスリキサイド / ウスチロキシン / リベロマイシン / ラジンコ-ル / ギルボカルシンの化学変換 / ホウ素含有化合物 / 多剤耐性克服 / 抗ガン物質
Research Abstract	本年度の各班員の研究実績は以下のとおりである。(瀬戸)多剤耐性癌細胞に有効な物質を検索し、放線菌の培養液から新規14員環マクロライドであるセコスリキサイドを単離し、その構造を決定した。本化合物はコルヒチン耐性のガン細胞に対するコルヒチンの有効濃度を顕著に減少させた。(岩崎)稲こうじ病菌より、ヒト固形ガン細胞に有効な環状ペプチド、ウスチロキシンを単離、構造決定を行った。(長田)EGFのマイトジェン活性の阻害物質をスクリ-ニングした結果、一放線菌株より新規抗生物質リベロマイシンを単離し、その構造を決定した。(吉田)動物細胞の周期特異的阻害剤をスクリ-ニングした結果、カビの一種がsrcおよびrasトランスフォ-ム細胞の形態を正常化する物質を生産していることを見出し、活性物質の単離を行った結果、ラジシコ-ルであることが判明した。(馬替)マクロファ-ジの代謝昂進作用および形態変化を指標として探索を行った結果、オ-レオシンおよびコンカナマイシンを単離した。これらの物質のマクロファ-ジによる腫瘍細胞障害活性に対する影響を検討したところ、有意な昂進効果が認められた。(長尾)抗癌活性を有するピペラジンジオン593Aをモデルとして、数種の新規なジケトピペラジン誘導体の合成を行った。現在その抗癌活性の試験を行っている。(柿沼)毒性の低い抗癌性物質であるギルボカルシンの溶解性や活性の改善を目的として化学変換を行い、溶解度の向上が認められた数種の化合物を得た。(根元)ホウ素原子と天然物質由来の有機部位を共有結合させた新規な誘導体を合成したところ、数種の化合物がin vitroで癌細胞に対し強力な成長阻害作用を示すことが判明した。(内藤)抗癌剤に対する多剤耐性を克服する薬剤を探索したところ、FKー506が種々の多剤耐性癌細胞において従来の抗癌財の感受性増強作用を示し、多剤耐性克服に有効であることが判明した。

Research Products

(24 results)

All Other

All Publications (24 results)

[Publications] Y.J.Kim: "Isolation and structural elucidation of stipiamide,a new antibiotic effective to multidrug-resistant cancer cells." J.Antibiotics. 44. 553-556 (1991)
[Publications] Y.Hayakawa: "Studies on the isotetracenone antibiotics.IV.Hatomarubigins A,B,C and D,new isotetracenone antibiotics effective to multidrug-resistant tumor cells." J.Antibiotics. 44. 1179-1186 (1991)
[Publications] Y,J,Kim: "Isolation and structural elucidation of sekothrixide,a new macrolide effective to overcome drug resistance of cancer cell." J.Antibiotics. 44. 1280-1282 (1991)
[Publications] K.Fujioka: "Isolation and characterization of atramycin a and atramycin b,new isotetracenone type antitumor antibiotics." J.Antibiotics. 44. 1025-1028 (1991)
[Publications] M.Matsumoto: "Stimulation of mammalian cell proliferation by lavanducyanin." J.Antibiotics. 44. 1471-1473 (1991)
[Publications] Y.Kato: "Studies on macrocyclic lactone antibiotics XIII.Antitubulin activity and cytotoxicity of rhizoxin derivatives.Synthesis of a photoaffinity derivative." J.Antibiotics. 44. 66-75 (1991)
[Publications] T.Sawada: "Fluorescent photoaffinity labeling derivatyives of rhizoxin." Biochem.Biophys.Res.Commun.178. 558-562 (1991)
[Publications] M.Miyoshi-Saitoh: "Dynemicins O,P and Q:Novel antibiotics related to dynemicin A.Isolation,characterization and biological activity." J.Antibiotics. 44. 1037-1044 (1991)
[Publications] Y.Li: "Interaction of phomopsin A with porcine brain tubulin.Inhibition of tubulin polymerization and binding at a rhizoxin binding site." Biochem.Phrmacol.43. 219-224 (1992)
[Publications] Y.Nagao: "Mechanisms of action of long chain fatty acid esters of podophyllotoxin aganist P388 lymphocytic leukemia in mice." Medicinal Chem.Res.1. 295-299 (1991)
[Publications] M.Naito: "Reversal of multidrug resistance by an immunosuppressive agent FK-506." Cancer Chemother.Phamacol.29. 348-353 (1991)
[Publications] M.Naito: "Two types of interaction between P-glycoprotein and ionophore antibiotics." J.Cell.Pharmacol.2. 263-267 (1991)
[Publications] S.Ishii: "Expression of 85-kDa protein of adriamycin-resistant tumor cells during hematopoietic differentiation of THP-1 and HEL cells." Jpn.J.Cancer Res.83. 107-112 (1992)
[Publications] H.Nemoto: "An improved and practical method for the synthesis of optically active diethyl tartrate dibenzyl ether." J.Org.Chem.56. 1321-1322 (1991)
[Publications] H.Nemoto: "Polyols of a cascade type as a water-solubilizing element of carborane derivatives for boron neutron capture therapy." J.Org.Chem.57. 435 (1992)
[Publications] Y.Yamoto: "Synthesis of carboranes containing nucleoside bases.Unexpectedly high cytostatic and cytocidal toxicity toward cancer cells." J.Chem.Soc.,Chem.Cummun.in press (1992)
[Publications] H.Osada: "Reveromycin A,a new antibiotic which inhibits the mitogenic activity of epidermal growth factor." J.Antibiotics. 44. 259-261 (1991)
[Publications] H.Osada: "Enopeptin A,a novel depsipeptide antibiotic with antibacteriophage activity." J.Antibiotics. 44. 1463-1466 (1991)
[Publications] H.Osada: "A new inhibitor of protein kinase C,RK-1409 (7-oxostaurosporine).I.Taxonomy and biological activity." J.Antibiotics. 45. 189-194 (1992)
[Publications] H.Osada: "A new indolocarbazole antibiotic,RK-286D." J.Antibiotics. 45. 278-279 (1992)
[Publications] H.J.Kwon: "Radicicol,and agent inducing the reversal of transformed phenotype of src-transformed fibroblasts." Biosci.Biotech.Biochem.(1992)
[Publications] T.Usui: "Uncoupled cell cycle without mitosis induced by a protein kinase inhibitor,K-252 a." J.Cell Biol.115. 1275-1282 (1991)
[Publications] Y.Hoshikawa: "Expression of differentiation-related markers in teratocarcinoma cells via histone hyperacetylation by trichostatin A." Agric.Biol.Chem.55. 1491-1495 (1991)
[Publications] K.Abe: "Highly synchronous culture of fibroblasts from G2 block caused by staurosporine,a potent inhibitor of protein kinases." Exp.Cell Res.192. 122-127 (1991)

1991 Fiscal Year Annual Research Report

新規構造を有する天然物由来抗癌物質に関する研究

Principal Investigator

瀬戸 治男 東京大学, 応用微生物研究所, 教授 (10013335)

Research Products

[Publications] Y.J.Kim: "Isolation and structural elucidation of stipiamide,a new antibiotic effective to multidrug-resistant cancer cells." J.Antibiotics. 44. 553-556 (1991)

[Publications] Y.Hayakawa: "Studies on the isotetracenone antibiotics.IV.Hatomarubigins A,B,C and D,new isotetracenone antibiotics effective to multidrug-resistant tumor cells." J.Antibiotics. 44. 1179-1186 (1991)

[Publications] Y,J,Kim: "Isolation and structural elucidation of sekothrixide,a new macrolide effective to overcome drug resistance of cancer cell." J.Antibiotics. 44. 1280-1282 (1991)

[Publications] K.Fujioka: "Isolation and characterization of atramycin a and atramycin b,new isotetracenone type antitumor antibiotics." J.Antibiotics. 44. 1025-1028 (1991)

[Publications] M.Matsumoto: "Stimulation of mammalian cell proliferation by lavanducyanin." J.Antibiotics. 44. 1471-1473 (1991)

[Publications] Y.Kato: "Studies on macrocyclic lactone antibiotics XIII.Antitubulin activity and cytotoxicity of rhizoxin derivatives.Synthesis of a photoaffinity derivative." J.Antibiotics. 44. 66-75 (1991)

[Publications] T.Sawada: "Fluorescent photoaffinity labeling derivatyives of rhizoxin." Biochem.Biophys.Res.Commun.178. 558-562 (1991)

[Publications] M.Miyoshi-Saitoh: "Dynemicins O,P and Q:Novel antibiotics related to dynemicin A.Isolation,characterization and biological activity." J.Antibiotics. 44. 1037-1044 (1991)

[Publications] Y.Li: "Interaction of phomopsin A with porcine brain tubulin.Inhibition of tubulin polymerization and binding at a rhizoxin binding site." Biochem.Phrmacol.43. 219-224 (1992)

[Publications] Y.Nagao: "Mechanisms of action of long chain fatty acid esters of podophyllotoxin aganist P388 lymphocytic leukemia in mice." Medicinal Chem.Res.1. 295-299 (1991)

[Publications] M.Naito: "Reversal of multidrug resistance by an immunosuppressive agent FK-506." Cancer Chemother.Phamacol.29. 348-353 (1991)

[Publications] M.Naito: "Two types of interaction between P-glycoprotein and ionophore antibiotics." J.Cell.Pharmacol.2. 263-267 (1991)

[Publications] S.Ishii: "Expression of 85-kDa protein of adriamycin-resistant tumor cells during hematopoietic differentiation of THP-1 and HEL cells." Jpn.J.Cancer Res.83. 107-112 (1992)

[Publications] H.Nemoto: "An improved and practical method for the synthesis of optically active diethyl tartrate dibenzyl ether." J.Org.Chem.56. 1321-1322 (1991)

[Publications] H.Nemoto: "Polyols of a cascade type as a water-solubilizing element of carborane derivatives for boron neutron capture therapy." J.Org.Chem.57. 435 (1992)

[Publications] Y.Yamoto: "Synthesis of carboranes containing nucleoside bases.Unexpectedly high cytostatic and cytocidal toxicity toward cancer cells." J.Chem.Soc.,Chem.Cummun.in press (1992)

[Publications] H.Osada: "Reveromycin A,a new antibiotic which inhibits the mitogenic activity of epidermal growth factor." J.Antibiotics. 44. 259-261 (1991)

[Publications] H.Osada: "Enopeptin A,a novel depsipeptide antibiotic with antibacteriophage activity." J.Antibiotics. 44. 1463-1466 (1991)

[Publications] H.Osada: "A new inhibitor of protein kinase C,RK-1409 (7-oxostaurosporine).I.Taxonomy and biological activity." J.Antibiotics. 45. 189-194 (1992)

[Publications] H.Osada: "A new indolocarbazole antibiotic,RK-286D." J.Antibiotics. 45. 278-279 (1992)

[Publications] H.J.Kwon: "Radicicol,and agent inducing the reversal of transformed phenotype of src-transformed fibroblasts." Biosci.Biotech.Biochem.(1992)

[Publications] T.Usui: "Uncoupled cell cycle without mitosis induced by a protein kinase inhibitor,K-252 a." J.Cell Biol.115. 1275-1282 (1991)

[Publications] Y.Hoshikawa: "Expression of differentiation-related markers in teratocarcinoma cells via histone hyperacetylation by trichostatin A." Agric.Biol.Chem.55. 1491-1495 (1991)

[Publications] K.Abe: "Highly synchronous culture of fibroblasts from G2 block caused by staurosporine,a potent inhibitor of protein kinases." Exp.Cell Res.192. 122-127 (1991)

瀬戸治男東京大学, 応用微生物研究所, 教授 (10013335)