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Molecular design of anticancer drug, α-NaGalase inhibitors for immunopotentiation

Research Project

Project/Area Number 10672090
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionThe University of Tokushima

Principal Investigator

HORI Hitoshi  Faculty of Engineering, The University of Tokushima, Professor, 工学部, 教授 (90119008)

Co-Investigator(Kenkyū-buntansha) NAGASAWA Hideko  Faculty of Engineering, The University of Tokushima, Associate Professor, 工学部, 講師 (90207994)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsα-N-acetyl gahctosamintdase / enzyme inhibitor / imnmnopotentiator / molecular design / anticancer drug / α-N-アセチルガラクトサミニダーゼ / 阻害活性 / 制がん剤分子設計 / がん細胞
Research Abstract

It was supposed as one of the mechanisms for immuno-suppression in cancer patients that macrophage activating factor (Gc MAF) could not be produced from a precursor, serum vitamin D-binding protein (Gc protein) due to deglycosylation by a-N-acetyl galactosaminidase (α-NaGalase). It was reported that α-NaGalase increased in cancer patients serum (Yamamoto, N. et al., 1998). To develop a immuno modulator of cancer therapy, the mechanism of immuno-suppression was defined by characterization of α-NaGalase in various tumor cells and α-NaGalase inhibitors was designed and synthesized as immuno potentiator.
1) α-NaGalase activities in tumor cell lysates from Hep G2 and HCT116 cells and normal cell lysates from Chang liver cell and isolated rat hepatocytes were measured. A high specific activity of a-NaGalase was found in tumor cell lines compare to normal cells. Because α-NaGalase deglycosylated exo-type substrate specifically, it was necessary to reinvestigate the deactivation mechanism of GcMAF by a-NaGalase.
2) Azasugar derivatives introduced spィイD12ィエD1 carbon to control a torsional angle between hydroxyl groups were designed and synthesized as a α-NaGalase inhibitor and an immunopotentiator, because a sugar-shaped alkaloid, swainsonine, was a α-mannosidase inhibitor and an immunopotentiator. Their activities of α-NaGalase inhibition and macrophage activation are now under investigation.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Zhu,J-W,H Nagasawa,H Hori et al.: "Elucidation of Strict Structural Requirements of Brefeldin A as an lnducer of Differentiation and Apoptosis"Bioorg.Med.Chem.. 8. 455-463 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagasawa,H.,H.Hori et al.: "Apoptosis induction in HCT116 cells by cytochalasins isolated from the fungus Daldinia vernicosa"Phytomedicine. 6. 403-409 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A-Z,Medhat,H Hori et al.: "Studies of methy 2-nitroimidazole-1-acetohydroxamate (KIN-804)1.Effect on free radical scavenging system in mice bearing Ehrlich ascites carcinoma"Biol.Pharm.Bull.. 23(2). 190-194 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A-Z,Medhat,H Hori et al.: "Studies of methy 2-nitroimidazole-1-acetohydroxamate (KIN-804)2.Effect on certain antioxidant enzyme system in mice bearing Ehrlich ascites carcinoma"Biol.Pharm.Bull.. 23(2). 195-198 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inomata,T,H Nagasawa,H Hori et al.: "The immunopotentiation Effects of the Bifunctional Radiosensitizer KIN-806 in comparison with its Analogs KIN-804 and KIN-844"Oncology Reports. 6(6). 1209-1212 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masunaga,S,K Ono,H Hori et al.: "Modification of tirapazamine-induced cytotoxicity in combination with mild hyperthermina:reference to effect on quiescent tumor cells"Int.J.Hyperthermia. 15(1). 7-16 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Inomata,S.Yoshida,H.Nagasawa,H.Hori et al.: "The immunopotentiation Effects of the Bifunctional Radiosensitizer KIN-806 in conmparison with its Analogs KIN-804A@and KIN-844"Oncology Reports. 6. 1209-1212 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] I.Shimizu,Y.Mizobuchi,F.liu,T.Miura,H.Hori et al.: "Effects of sho-saiko-to, a japanese herbal medicine,on hepatic fibrosis in rats"Hepatology. 29. 49-60 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H.Hori,M.Ishibashi,H.Nagasawa,Y.Uto,et al.: "Enhancement effect of methyl a-D-glucoside for inhibitory effects of antioxidants on ADP/Fe2+-induced lipid perox idation in rat liver mitochondria"Adv.Mxp.Med.Biol.(Oxygen Transport Tissue XXI). XXI. 395-402 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Inomata,S.Kariya,H.Nagasawa,H.Hori,et al.: "The Effects of the Lung Metastasis Suppressioh of the Bifunctional New Radiosensitizer KIN-806"Int.J.Mol.Med.. 4. 257-260 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Masunaga,H.Hori,H.Nagasawa,Y.Uto et al.: "Potentially lethal damage repair by total and quiscent tumor cells following various DNA-damaging treatments"Radiation Medicine. 17. 259-264 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K Ohkura,H Hori: "Analysis of structure-permeability of correlation of nitrophenol analogues in newborn rat abdominal skin using semiempirical moleular orbital calculation"Bioorg.Med.Chem.. 7. 309-314 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kasai,S.,Nagasawa,H.,H.Hori et al.: "TX-1877:Design,Synthesis,and Biological Aeitivities as a BRM-functional Hypoxic Cell Radiosensitizer"Int.J.Radiation Oncology Biol.Phys. 42(4). 799-802 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masunage,S,K Oho,H Hori et al.: "Enhancement of cisplatin sensitivity of quiescent cells in solid tumors by combined treantment with tirapazamine and low-temperature hyperthermia"Radiation Medicine. 16(6). 441-448 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masunaga,S,K Ono,Y Sakurai,H Hori et al.: "Applicability of Combination with Tirapazamine in Boron Meutron Capture Therapy"Jpn.J.Cancer Res.89(7):768-774(1998). 87(7). 768-774 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Goto,S,K-X Chen,S Oda,H Hori,and H Terada: "Dynamic Structural Features of Macrocyclic Cytochalasin Analogues Responsible for Their Hexose Transport Inhibiton"J.Am.Chem.Soc.. 120. 2457-2463 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhu, J-W, H Nagasawa, and H Hori et al.: "Elucidation of Strict Structural Requirements of Brefeldin A as an Inducer of Differentiation and Apoptosis."Bioorg Med. Chem.. 8. 455-463 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagasawa. H., H. Hori et al.: "Apoptosis induction in HCT116 cells by cytochalasins isolated from the fungus Daldinia vernicosa."Phytomedicine. 6(6). 403-409 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A-Z, Medhat, H Hori, H Nagasawa et al.: "Studies of methyl 2-nitroimidazole- 1- acetohydroxamate (KIN-804) 1. Effect on free radical scavenging system in mice bearing Ehrlich ascites carcinoma."Biol. Pharm. Bull.. 23(2). 190-194 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A-Z, Medhat, H Hori, H Nagasawa et al.: "Studies of methyl 2-nitroimidazole- 1- acetohydroxamate (KIN-804) 2. Effect on certain antioxidant enzyme system in mice bearing Ehrlich ascites carcinoma."Biol. Pharm. Bull.. 23(2). 195-198 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohkura, K and H Hori: "Analysis of structure-permeability of correlation of nitrophenol analogues in newborn rat abdominal skin using semiempirical molecular orbital calculation."Bioorg. Med. Chem.. 7. 309-314 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu, I, Y.-R. Ma, Y Mizobuchi, F Liu, T Miura, Y Nakai, M Yasuda, M Shiba, T Horie, S Amagaya, N Kawada, H Hori, and S Ito: "Effects of sho-saiko-to, a japanese herbal medicine, on hepatic fibrosis in rats."Hepatology. 29(1). 49-60 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hori, H., M. Ishibashi, S. B. Mohamad, H. Nagasawa, Y. Uto, H. Sakamaki, N. Pan, K. Ohkura, and S. Nishibe: "Enhancement effect of methyl α-D-glucoside for inhibitory effects of antioxidants on ADP/FeィイD12+ィエD1-induced lipid peroxidation in rat liver mitochondria."Adv. Exp. Med. Bio. (Oxygen Transport to Tissue XXI). 395-402 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inomata, H Nagasawa, H Hori et al.: "The Effects of the Lung Metastasis Suppression of the Bifunctional New Radiosensitizer KIN-806."Int. J. Mol. Med. 4(3). 257-260 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inomata, T, H Nagasawa, H Hori et al.: "The immunopotentiation Effects of the Bifunctional Radiosensitizer KIN-806 in comparison with its Analogs KIN-804 and KIN-844."Oncology Reports. 6(6). 1209-1212 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masunaga, S, K Ono, H Hori et al.: "Modification of tirapazamine-induced cytotoxicity in combination with mild hyperthermina : reference to effect on quiescent tumor cells."Int. J. Hyperthermia. 15(1). 7-16 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masunaga, S, K Ono, H Hori et al.: "Potentially lethal damage repair by total and quiscent tumor cells following various DNA-damaging treatments."Radiation Medicine. 17(4). 259-264 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kasai, S., H. Nagasawa, H. Hori et al.: "TX-1877 : Design, Synthesis, and Biological Activities as a BRM-functional Hypoxic Cell Radiosensitizer."Int. J. Badiation Oncology Biol. Phys. 42(4). 799-802 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masunaga, S, K Ono, H Hori et al.: "Enhancement of cisplatin sensitivity of quiescent cells in solid tumors by combined treatment with tirapazamine and low-temperature hyperthermia."Badiation Medicine. 16(6). 441-448 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masunaga, S, K Ono, Y Sakurai, H Hori et al.: "Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy."Jpn. J. Pancer Res.. 89(7). 768-774 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Goto, S, K.-X Chen, S Oda, H Hori, and H Terada: "Dynamic Structural Features of Macro-cyclic Cytochalasin Analogues Responsible for Their Hexose Taansport Inhibition."J. Am. Chem. Soc.. 120. 2457-2463 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhu,J-W,H Nagasawa,H Hori et al.: "Elucidation of Strict Structural Requirements of Brefeldin A as an Inducer of Differentination and Apoptosis."Bioorg.Med.Chem.. 8. 455-463 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagasawa,H.,H.Hori et al.: "Apoptosis induction in HCT116 cells by cytochalasins isolated from the fungus Daldinia vernicosa."Phytomedicine. 6. 403-409 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] A-Z,Medhat,H Hori et.al.: "Studies of methyl2-nitroimidazole-1-acetohydroxamate(KIN-804)1.Effect on free radical scavenging system in mice bearing Ehrlich ascites carcinoma"Biol.Pharm.Bull.. 23(2). 190-194 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] A-Z,Medhat,H Hori et.al.: "Studies of methyl2-nitroimidazole-2-acetohydroxamate(KIN-804)1.Effect on certain antioxidant enzyme system in mice bearing Ehrlich ascites carcinoma"Biol.Pharm.Bull.. 23(2). 195-198 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inomata,T,H Nagasawa,H Hori et al.: "The immunopotentiation Effects of the Bifunctional Radiosensitizer KIN-806 in comparison with its Analogs KIN-804 and KIN-844."Oncology Reports. 6(6). 1209-1212 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masunaga,S,K Ono,H Hori et al.: "Modification of tirapazamine-induced cytotoxicity in combination with mild hyperthermina:reference to effect on quiescent tumor cells."Int.J.Hyperthermia.. 15(1). 7-16 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Inomata,S.Yoshida,H,Nagasawa,H.Hori et al.: "The immunopotentiation Effects of the Bifunctional Radiosensitizer KIN-806 in comparison with its Analogs KIN-804Å@ and KIN-844."Oncology Reports. 6. 1209-1212 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] I.Shimizu,Y.Mizobuchi,F.Liu,T.Miura,H.Hori et al.: "Effects of sho-saiko-to,a japanese herbal medicine,on hepatic fibrosis in rats"Hepatalogy. 29. 49-60 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Hori,M.Ishibashi,H.Nagasawa,Y.Uto,et al.: "Enhancement effect of methyl a-D-glucoside for inhibitory effects of antioxidants on ADP/Fe2+-induced lipid perox idation in rat liver mitochondria"Adv.Exp.Med.Biol.(Oxygen Transport to Tissue XXI). XXI. 395-402 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Inomata,S.Kariya,H.Nagasawa,H.Hori,et al.: "The Effects of the Lung Metastasis Suppression of the Bifunctional New Radiosensitizer KIN-806"Int.J.Mol.Med.. 4. 257-260 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Masunaga,H.Hori,H.Nagasawa,Y.Uto et al.: "Potentially lethal damage repair by total and quiscent tumor cells following various DNA-damaging treatments"Radiation Medicine. 17. 259-264 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Ohkura,H.Hori: "Analysis of structure-permeability of correlation of nitrophenol analogues in newborn at abdominal skin using semiempirical molecular orbital calculation"Bioorg.Med.Chem.. 7. 309-314 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Goto,S.,Chen,K.X.,Oda,S.,Hori,H.et al.: "Dynamic structural features of macrocyclic cytochalasin analogues responsible for their hexose transport inhibition." J.Am.Chem.Soc.120. 2457-2463 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kasai,S.,Nagasawa,H.,& Hori,H.et al.: "TX-1877:design,synthesis,and biological actibities as a BRM-functional hypozic cell radiosensitizer." Int.J.Radiation Oncology Biol.Phys.42(4). 799-802 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masunaga,S-1,Ono,K.,Hon,H.et al.: "Wnhancement ofcisplatin sensitibity of quiescent cells in solid tumors by combined treatment with tirapazamine and low-temperature hyperthermia." Radiation Medicine. 16(6). 441-448 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masunaga,S.i-.,Ono,K.,Sakurai,Y.,Hori,H.,et al.: "Applicability of Combination with Tirapazamine in Boron Neutron Capture Therapy." Jpn.J.Cancer Res.89(7). 768-774 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] MIsobuchi,Y.,Shimizu,I.,Yasuda,M.,Hori,et al.: "Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum." J.Hepatology. 29(6). 933-943 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masunaga,S.-I.,Ono,K.,Hori,H.et al.: "Modification of tirapazamine-induced cytotoxicity in combination with mild hyperthermina:reference to effect on quiescent tumor cells." Int.J.Hyoertheermia. 15(1). 7-16 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimizu,I.,Ma,Y.R.,Mizobuchi,Y.Hori,H.,et al.: "Effects of sho-saiko-to,a jaoanese herbal medicine,on hepatic fibrosis in rats." Hepatology. 29(1). 49-60 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohkura,K.,& Hori,H.: "Analysis of structure-oermeability of correlation of nitrophenol analogues in newborn rat abdominal skin using semiempirical moleular orbital calculation." Bioorg.Med.Chem.6(in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-11-11  

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