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Development of Anti-malarial Drug and it's Molecular Target

Research Project

Project/Area Number 08281105
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionOkayama University

Principal Investigator

WATAYA Yusuke  Okayama University, Graduate School of Nature. Professor, 大学院・薬学研究科, 教授 (90127598)

Co-Investigator(Kenkyū-buntansha) KITA Kiyoshi  The University of Tokyo, Graduate School of Mediciile, Professor, 大学院・医学系研究科, 教授 (90134444)
ITAI Akiko  Kitazato Institute, Director, 部長研究員 (60012647)
MATSUDA Akira  Hokkaido University, Graduate School of Pharmacy, Professor, 大学院・薬学研究科, 教授 (90157313)
SEKIMIZU Kazuhisa  The Univ. of Tokyo, Graduate School of Pharmacy, Professor, 大学院・薬学系研究科, 教授 (90126095)
KIMURA Masatsugu  Osaka City University, School of Medicine, Research Associate, 医学部, 助手 (60195378)
MORIYAMA Yoshiuori  Okayama University, Graduate School of Nature, Professor (10150658)
Project Period (FY) 1996 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥194,000,000 (Direct Cost: ¥194,000,000)
Fiscal Year 1999: ¥42,000,000 (Direct Cost: ¥42,000,000)
Fiscal Year 1998: ¥44,000,000 (Direct Cost: ¥44,000,000)
Fiscal Year 1997: ¥44,700,000 (Direct Cost: ¥44,700,000)
Fiscal Year 1996: ¥63,300,000 (Direct Cost: ¥63,300,000)
KeywordsMalaria / Anti-malaria drug / Screening / antisense / tropical fever / protozoa / Plasmodium falciparum / target molecule / ミトコンドリア / ATPase / マラリア治療薬 / スクリーニンヅ / 熱帯熱マラリア / インターネット
Research Abstract

The research project involves scientists from numerous research fields and has already contributed greately to the research of malaria by developing new antimalarial agents.
1) We are screening 4,635 samples containing natural products, organic compounds, microorganism-derived products, combinatorial bio-compounds and marine products that are alleged to have antimalarial activity. As the results, 165 compounds with high selective antimalarial activity (selective cytotoxicity is over 100) for Plasmodium falciparum were obtained using in vitro assay system. The study of in vitro and in vivo demonstrated that 1,2,6,7-tetraoxaspiro[7.11]nonadecane is the attractive prototype in a new class of inexpensive peroxide antimalarial drugs.
2) We have made a chimera-gene vector named CMC expressing a chimeric protein of P-ATPase (PfATP6 in P. falciparum) and chicken Ca-ATPase to demonstrate these functions essential for malaria parasites. PfATPase were expressed at the stage of trophozoites in P. fa … More lciparum.
3) We have identified a NSF homologue in Plasmodium falciparum (pfNSF) which is exported to extracellular space and localized with intraerythrocytic vesicles. The vesicular transport mechanism is involved in protein export to erythrocyte during intraerythrocytic development of malaria parasite.
4) We have isolated Ip subunit of Plasmodium succinate-ubiquinone reductase (complex II) in themitochondrial respiratory chains which is good targets for chemotherapy. Western blot using antibody against the recombinant Ip and northern analysis clearly showed that expression of parasite complex II is highest at late trophozoite/schizont stages of P. falciparum.
5) Phosphorothioate (PS) antisense (AS) oligonucleotides(ODNs) have widely been used as a tool to identify a role of a target protein. However, we tested several PSAS-ODNs and their sense ODNs against several enzymes in P. falciparum without significantly different effects. On the other hands, ODNs having phsphodiester (PO) bond, which are resistant to endo- and exo-nucleases, showed that AS-ODNs are more effective than their sense ODNs. Using this ODN, we found that succinate dehydrogenase was functionally active in P. falciparum and is a target enzyme to search anti-parasitic agents.
6) Our goal is to establish animal models for human malaria infection where one can evaluate candidates for anti-malaria drugs. We are also trying to understand molecular mechanisms for the invasion of the parasite into red blood cells. We already constructed mutant mice disrupting the gene encoding Duffy antigen by gene targeting technique.
7) A three-dimensional structure model of dihydrofolate reductase(DHFR) domain of P. falciparum DHFR-TS was predicted based on the X-ray structures of other species. It was used to design new inhibitors effective to cycloguanil-resistant FCR3 strain. As result, highly effective and selective inhibitors were developed. We also found new inhibitors with different skeletal stuructures from known DHFR inhibitors. Less

Report

(5 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (119 results)

All Other

All Publications (119 results)

  • [Publications] Kim, H.-S.: "Synthesis and antimalarial activity of novel medium-sized 1,2,4,5-tetraoxacycloalkanes"J. Med. Chem.. 44. 2357-2361 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takasu, K.: "Synthesis of a novel artemisinin analog having potent antimalarial activity"Heterocycles. 54. 607-610 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takaya, T.: "Novel guaianoids, nardoguaianone A-D, from Nardostachys chinensis roots and their antinociceptive and antimalarial activities"Tetrahedron. 56. 7673-7678 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh, T.: "Synthesis of novel ferrocenyl sugars and their antimalarial activities"Bioorg. Med. Chem. Lett.. 10. 1657-1659 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nonami, Y.: "Synthesis, crystal structure and anti-malarial activity of functionalized spiro-1,2,4,5-tetraoxacycloalkanes from unsaturated hydroperoxy peracetals"Tetrahedron Letters. 41. 4681-4684 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokuyasu, T.: "Synthesis ans anti-malarial activity of Yingzhaosu A analogues from unsaturated hydroperoxy acetals"Tetrahedron Letters. 41. 3145-3148 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kim, H.S.: "Synthesis and antimalarial activity of novel medium-sized 1,2,4,5-tetraoxacycloalkanes"J. Med. Chem.. 44. 2357-2361 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takasu, K.: "Synthesis of a novel artemisinin analog having potent antimalarial activity"Heterocycles. 54. 607-610 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takaya, T.: "Novel guaianoids, nardoguaianone A-D, from Nardostachys Chinensis roots and their antinociceptive and antimalarial activities"Tetrahedron. 56. 7673-7678 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh, T.: "Synthesis of novel ferrocenyl sugars and their antimalarial activities"Bioorg. Med. Chem. Lett.. 10. 1657-1659 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nonami, Y.: "Synthesis, crystal structure and anti-malariai activity of functionalized spiro-1,2,4,5-tetraoxacycloalkanes from unsaturated hydroperoxy peracetals"Tetrahedron Letters. 41. 4681-4684 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokuyasu, T.: "Synthesis ans anti-malarial activity of Yingzhaosu A analogues from unsaturated hydroperoxy acetals"Tetlahedron Letters. 41. 3145-3148 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 綿矢 有佑: "抗マラリア薬"治療. 81. 2261-2268 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 北 潔: "薬剤耐性マラリアとその克服"治療. 81. 2453-2460 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Iwasa: "Structure-activity relationships of quaternary protoberberine alkaloids having antimalarial activity"Evr.J.Med.Chem.. 34. 1077-1083 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.-S.Kim: "Synthesis and antimalarial activity of cyclic peroxides,1,2,4,5,7-pentoxocanes and 1,2,4,5-teroxanes"J.Med.Chem.. 42. 2604-2609 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.-S.Kim: "A potent in vitro antimalarial activity of 3,15-di-O-acetylbruceolide against Plasmodium berfhei infection in mice"Parasitol.Int. 48. 271-274 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.-S.Kim: "Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent"Biol.Pharm.Bull.. 22. 532-534 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Tsuchiya: "Synthesis,crystal structure and anti,alarial activity oh novel medium-sized 1,2,4,5-tetraoxacycloalkanes"Tetrahedron Lett.. 40. 4077-4080 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Takeuchi: "Synthesis and Antimalarial Activity of DL-Deoxyfebrifugine"Heterocycles. 51. 1869-1875 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Kobayashi: "Catalytic Asymmetric Synthesis of Antimalarial Alkaloids Febrifugine and Isofebrifugine and Their Biological Activity"J.Org.Chem..

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Takaya: "NewType of Febrifugine Analogues,Bearing a Quinolizidine Moiety,Show Potent Antimalarial Activity against Plasmodium malaria Parasite"J.Med.Chem.. 42. 3163-3166 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.-S.Kim: "Synthetic Methods for Unsymmetrically-substituted 1,2,4,5-tetraxnes and of 1,2,4,5,7-pentoxacanes"J.Chem.Soc.Parkin Trans.1. 1867-1870 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Takeo: "Succinate dehydrogenase in Plasmodium falciparum mitochondria:Molecular characterization of the SDHA and SDHB genes for the catalytic subunits,the flavoprotein (Fp) and iron-sulfur (Ip) subunits"Mol.Biochem.Barasitol.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] N.Sakihara: "Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum,the malignant human malaria parasite"Gene. 230. 47-54 (1990)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Kimura: "Gametocyte-dominant expression of a novel P-type ATPase in Plasmodium yoelii"Mol.Biochem.Parasitol.. 104. 331-336 (1990)

    • Related Report
      1999 Annual Research Report
  • [Publications] R.Koyanagi-Katsuta: "Apotosis of mouse embryonic stem cells induced by single cell suspension"Tissue & Cell. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] N.Ikemoto: "Antisence origonmicloetides:Useful tool for search and assessment of new targets for anti-malarial drugs"Nucleic Acids Sympo.Ser.. 42. 89-90 (1990)

    • Related Report
      1999 Annual Research Report
  • [Publications] H-S.Kim: "Cycloprodigiosin hydrochloride obtained from Pseudoalteromonas denitrificans is a potent antimalarial agent" Biol.Pharm.Bull.(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] M.U.Ferreira: "Stable patterns of allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from Southern Vietnam." J.Eukaryotic Microbiol. 45. 131-136 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Zhou: "High prevalence of Plasmodium malariae and P.ovale in malaria patients along the Thai-Mvanmar Border.as revealed by acridine orange staining and PCR-based diagnoses." Trop.Med. & Int.Health. 11. 304-312 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.U.Ferreira: "Allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from southwestern Brazilian Amazon." Am.J.Trop.Med.Hyg.59. 474-480 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Q.Liu: "Sequence variation in the small-subunit rRNA gene of Plasmodium malariae and prevalence of isolates with the variant sequence in Sichuan, China." J.Clinical Microbiol.36. 3378-3381 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Iwasa: "Antimalarial activity and structure-relationships of protoberberine alkaloids." Eur.J.Med.Chem.33. 65-69 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.-S.Kim: "A potent animalarial activity of5-fluoroorotate in combination with sulfamonomethoxine against Plasmoduium falciparum in vitroand Plasmodium berghei in mice." Parasitol.Int.47. 59-67 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Takahara: "Antimalarial Activity and Nucleoside Transport Inhibitory Activity of the Triterpenic Constituents of Cim icifuga spp" Biochem.Pharm.Bull.21. 823-828 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Nakamura: "Deoxyribonucleoside Triphosphates in Mouse Fetal Liver Cells Assayed by High Pressure Liquid Chromatograpy." Toxicology Methods. 8. 11-16 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Takaya: "Novel antimalarial guaiane-type sesquiterpenoids from Nardostachys chinensis roots." Tetrahedron Lett.39. 1361-1364 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Murakami: "Anti-malarial activities of acylated bruceolide derivatives." Bioorg.Med.Chem.Letters.8. 459-461 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Miyata: "Antimararial activities in vitro of homoprotoberberine derivatives.Desigen of novel antimaralials and structure-activity relationship analysis." Helerocycles. 49. 101-104 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Miyaoka: "Antimalarial activity of kalihinol A and new relative diterpenoids from the okinawan sponge, Acanthella sp." Tetrahedron. 54. 13467-13474 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Ueno: "Synthesis of oligodexynucleosides containing 4'a-C-aminoalkylthymidines and their thermal stability and nuclease-resistance properties." Nucleic Acids Symposium Series. 39. 13-14 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Wataya: "Usefulness of a new DNA diagnostic method for malaria ; microfiter plate-hybridization" Tokai J.Exp.Clin.Med.23. 87-88 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Meiji: "Malaria research in Solomon Island" Inter Croup Corporation (Tokyo), 192 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Iwasa: "Antimalarial activity and structure-relationships of protoberberine alkaloids." Eur.J.Med.Chem.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Kimura: "Identification of the four species of human malaria parasites by nested PCR that targets variant sequences in the small subunit rRAN gene." Parasitol.Int.46. 91-95 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Toyada: "Lead discovery of inhibitors of the dihydrofolate reductase domain of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase." Biochem.Biophys.Res.Commun.235. 515-519 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Itai: "Advanced computational docking of two teleocidin congeners to cys2 domain of protein kinase Cδ." Chem.Pharm.Bull.45. 573-575 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Hirawake: "Variation in the C-terminal repeats of the knob-associated histidine-rich protein of Plasmodium falciparum." Biochim.Biophys.Acta. 1360. 105-108 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] P.K.C.Lim: "Species-specific diagnosis of human malaria by the polymerase chain reaction." Int.Med.Res.J.1. 69-72 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Kita: "Cytochromes in the respiratory chain of helminth mitochondria." Int.J.Parasitol.27. 617-630 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] O.Kaneko: "Plasmodium falciparum : allelic variation in the merozoite surface protein I gene in wild isolates from southern Vietnam." Exp.Parasitol.86. 45-47 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.U.Ferreira: "Stable patterns of allelic diversity at the merozoite surface protein-1 locus of Plasmodium falciparum in clinical isolates from Southern Vietnam." J.Eukaryotic Microbiol.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Shuto: "New neplanocin analogues. IX (.A practecal preparation of (6'R) -6'-C-methylneplanocin A (RMNPA),a potent antiviral agent,by the diastereoselective enzymatic deamination as a key-step,and the determination of its 6'-configuration." Chem.Pharm.Bull.45. 138-142 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Miyake: "A Variant of Plasmodium ovale ; Analysis of its 18S Ribosomal RNA Gene Sequence." Nucleic Acids Symposium Series.37. 293-294 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.-S.Kim: "A potent antimalarial activity of 5-fluoroorotate in combination with sulfamonomethoxine against Plasmodium falciparum in vitro and Plasmodium berghei in mice." Parasitol.Int.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Takaya: "Novel antimalarial guaiane-type sesquiterpenoids from Nardostachys chinensis roots." Tetrahedron Letters.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] 北潔: "マラリア制圧の夢と現実" ファルマシア. 32(8). 932-937 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 木村幹男: "急激な原虫数の増加と黒水熱を来した重症熱帯熱マラリアの症例" 治療学. 31. 105-107 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] F.Kawamoto: "Sequence variation in the 18S rRNA gene,a Target for PCR-based Malaria Diagnosis,in Plasmodium Ovale from Southern Vietnam" J.Clinical Microbiol.34. 2287-2289 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] O.Kaneko: "Plasmodium falciparum : Variation in Block 4 of the Precursor to the Major Merozoite Surface Proteins (MSP1) in Natural Populations" Exp.Parasitol. 84. 92-95 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] R.K.B.Brobey: "Recombinant Plasmodium falciparum dihydrofolate reductase-based in vitro screen for antifolate antimalarials" Mol.Biochem.Parasitol.84. 225-237 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Inoue: "Molecular cloning of a RNA binding protein,S1-1." Nucleic.Acid Res.15. 2990-2997 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Kageyama: "Promotive action of acylated ascorbate on cellular DNA synthesis and growth at low doses in contrast to inhibitory action at high doses or upon combination with hyperthermia" J.Cancer Res.& Clinical Oncol.122(1). 41-44 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] O.Kaneko: "Plasmodium falciparum : Allelic variation in the Merozoite Surface Protein 1 gene in wild isolates from southern Vietnam" Exp.Parasitol.(in press). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] W.Wang: "Inactivation of inosine 5′-monophosphate dehydrogenase by the antiviral agent 5-ethynyl-1-b-D-ribofuranosylimidazole-4-carboxamide 5′-monophosphate" Biochemistry. 35. 95-101 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Minakawa: "Synthesis of 3-halo-3-deazainosines : Conformational lock with the halogen at the 3-position of the 3-deazainosine in anti-conformation" Heterocycles. 42. 149-154 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shuto: "Synthesis of 2′-deoxy and 5′-phosphate derivatives of bredinin. A photochemical imidazole-ring cleavage and subsequent reconstruction of the base moiety" Tetrahedron Lett.37. 187-190 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Ono: "Highly stereoselective nucleophilic addition to cyclopropyl carbonyls : the facial selectivity in the cyclopropyl ketones is opposite to that in the corresponding aldehyde" Tetrahedron Lett.37. 221-224 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Minakawa: "Synthesis of 5-amino-4-imidazolecarboxamide (AICA) deoxyribosides from deoxyinosines and their conversion into 3-deazapurine derivatives" Chem.Pharm.Bull.44. 288-295 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shuto: "Synthesis of (+) and (-)-milnaciprans and their conformationally restricted analogs" Tetrahedron Lett.37. 641-644 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Iino: "Stereoselective synthesis of (2′S)-2′C-alkyl-2′-deoxyuridine." Nucleosides Nucleotides. 15. 169-181 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Minakawa: "Synthesis and antileukemic activity of 5-carbon-substituted l-b-D-ribofuranosyl-imidazole-4-carboxamides" Nucleosides Nucleotides. 15. 251-263 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Yoshimura: "A novel synthesis of new antineoplastic 2′-deoxy-2′-substituted-4′-thiocytidines" J.Org.Chem.61. 822-823 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shuto: "Conformational restriction by repulsion between adjacent substituents on a cyclopropane ring : Design and enantioselective synthesis of 1-phenyl-2-(1-aminoalkyl)-cyclopropane-N,N-diethylcarboxamides as potent NMDA receptor antagonists" J.Org.Chem.61. 915-923 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Kakefuda: "Synthesis of DNA containing oxetanocin A and (2R,3R)-2-C-(adenin-9-yl)-1,4-anhydro-2,3-dideoxy-3-C-hudroxymethyl-D-arabitol" Tetrahedron. 52. 2863-2876 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Awano: "Synthesis and antiviral activity of 5-substituted (2′S)-2′-dexy-2′-C-methylcytidinesand -uridines" Arch.Pharm.Pharm.Med.Chem.329. 66-72 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Matsuda: "Polydeoxyaminohexopyranosylnucleosides. Synthesis of 1-(2,3,4-trideoxy-3-nitro-b-D-erythro- and threo-hexopyranosyl)-uracils from uridine" Nucleosides Nucleotides. 15. 205-217 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] X.Gu: "Interaction of tRNA (uracil-5-)-methyltransferase with NO2Ura-tRNA" Nucleic Acids Res.24. 1059-1064 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shuto: "Enzymatic Synthesis of 5′-phosphatidyl derivaties of 1-(2-C-cyano-2-deoxy-b-D-arabino-pentofuranosyl)cytosine (CNDAC) and their notable antiumor effects in mice" Bioorg.Med.Chem.Lett.6. 1021-1024 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 松田 彰: "固形がんに有効な新規ヌクレオシド、CNDACの分子設計" Jpn.J.Cancer Chemother.23. 202-210 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 松田 彰: "リレー連載「化学はどこまで生命に近づけるか」第10回抗がん剤「がんと戦うために化学を使おう」" 化学. 51. 180-183 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 周東 智: "リン脂質の経口吸収特性を利用する制癌剤のリンパ系ターゲテイング-制癌疑似リン脂質5′-ホスファチジル-FURの設計・合成および生物活性-" Drug Delivery System. 11. 81-88 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shuto: "Synthesis and Potent Antiviral Activity of 6′-Homoneplanocin A (HNPA)" J.Med.Chem.39. 2392-2399 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 松田 彰: "環状ADPリボース-Ca2_+動員に関与する新しいセカンドメッセンジャー-" ファルマシア. 32. 810-816 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Aoyagi: "Effects of 2′-a-and 2′-b-bromo-2′-deoxyadenosine on oligonucleotide hybridization and nuclease stability" Bioorg.Med.Chem.Lett.6. 1573-1576 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Obara: "A potent adenosylhomocysteine hydrolase inhibitor lacking antiviral activity. Synthesis and antiviral activity of 6′-carboxylic acid derivatives of neplanocin A" Nucleosides Nucleotides. 15. 1157-1167 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Kira: "The FIAU derivative (2′S)-2′-deoxy-2′-C-methyl-5-iodouridine (SMIU) is a novel,less cytotoxic and potent anti-HSV and anti-VZV agent" Antiviral Chem.Chemother.7. 209-212 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Matsuda: "1-(3-C-Ethynyl-b-D-ribo-pentofuranosyl)uracil as a potential broad spectrum multifunctional antitumor nucleoside" Bioorg.Med.Chem.Lett.6. 1887-1892 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Minakawaw: "Synthesis of [2-2H]-5-ethynyl-1-(b-D-ribofuranosyl)imidazole-4-carboxamide and 5-ethynyl-1-([5-3H]-b-D-ribofuranosyl)imidazole-4-carboxamide (EICAR)" J.Labelled Compd.Radiopharm.38. 809-824 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.E.A.Hassan: "Conversion of (Z)-2′-cyanomethylene-2′-deoxyuridines into their (E)-isomers via addition of thiophenol to the cyanomethylene moiety followed by oxidative syn-elimination reactions" J.Org.Chem.61. 6261-6267 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shuto: "Synthesis,antitumor effects,and possible enzymatic activation mechanism of 5′-phosphatidyl-2′-deoxy-2′-methylenecytidine (DMDC)" Bioorg.Med.Chem.Lett.6. 2177-2182 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Ono: "Cell kill kinetics of an antineoplastic nucleoside,1-(2-deoxy-2-methylene-b-D-erythoro-pentofuranosyl)cytosine" Biochem.Pharmacol.52. 1279-1285 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Obara: "Synthesis and antiviral activity of 2-halo derivatives of neplanocin A" J.Med.Chem.19. 3847-3852 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Miura: "In vitro and in vivo antitumor activity of a novel mucleoside,4′-thio-2′-deoxy-2′-methylidnecytidine" Bio.Pharm.Bull.

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.I.Pavlov: "Base analog N6-hydroxylaminopurine mutagenesis in Escherichia coli : molecular specificity and genetic control" Mutation Res.357. 1-15 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Tabata: "Antitumor effect of a novel multifunctional antitumor nucleoside,3′-ethynylcytidine,on human cancers" Oncology Reports. 3. 1029-1034 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Nishizono: "Synthesis of thietane nucleosides via the Pummerer reaction as a key step" Tetrahedron Lett.37. 7569-7572 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Shuto: "Synthesis and biological activity of conformationally restricted analogs of milnacipran : (1S,2R)-1-Phenyl-2-[(S)-1-aminopropyl]cyclopropane-N,N-diethylcarboxamide,an efficient noncompetitive N-methyl-D-aspartic acid receptor antagonist" J.Med.Chem.39. 4844-4852 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Hattori: "1-(3-C-Ethynyl-b-D-ribo-pentofuranosyl)cytosine (ECyd),1-(3-C-Ethynyl-b-D-ribo-pentofuranosyl)uracil (EUrd),and their Nucleobase Analogues as New Potential Multifunctional Antitumor Nucleosides with a Broad Spectrum of Activity" J.Med.Chem.39. 5005-5011 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Ohshima: "Damage induced by hydroxyl radicals generated in the hydration layer of g-irradiated frozen aqueous solution of DNA" J.Radiat.Res.37. 199-207 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Nishizono: "Synthesis of novel nucleosides with a thietane ring" Nucleic Acids Sympo.Series. 35. 59-60 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Takatori: "Antitumor mechanism of 3′-ethynylcytidine (ECyd) and 3′-ethynyluridine (EUrd)" Nucleic Acids Sympo.Series. 35. 209-210 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] F.Saruta: "Cloning of a cDNA ecoding the small subunit of cytochrome b558 (cybS) of mitochondrial fumarate reductase (Complex II) from adult Ascaris suum" Biochim.Biophys.Acta. 276. 1-5 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Ogawa: "Dnak heat shock protein of Escherichia coli maintains the negative supercoiling of DNA against thermal stress" J.Biol.Chem.271. 29407-29414 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Minagawa: "An antibiotic,Ascofuranone,specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei" Mol.Biochem.Parasitol.81. 127-126 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] P.K.C.Lim: "Cytochrome c oxidase III (COIII) gene of Plasmodium vivax : Complete coding sequence and its expression in the erythrocytic stage of the parasite" Jpn.J.Parasitol.45. 373-383 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Nomura: "Incorporation of 5-(N-aminoalkyl)carbamoyl-2′-deoxycytidines into oligodeoxyribonucleotides by a convenient post-synthetic modification method" Bioorg.Med.Chem.Lett.6. 2811-2816 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Ueno: "Facile synthesis of 5′-5′-linked oligodeoxyribonucleotides with the potential for triple-helix formation" Bioorg.Med.Chem.Lett.6. 2817-2822 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Ichikawa: "Synthesis of 3′-b-branched-chain ribonucleosides via samarium diiodide-mediated intramolecular Reformatsky type reaction and their antitumor activities" Nucleic Acids Sympo.Series. 35. 13-14 (1996)

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      1996 Annual Research Report
  • [Publications] Y.Yoshimura: "Synthesis of 2′-deoxy-2′-fluoro-4′-thioarabinonucleosides as potential antitumor and antiviral agents from D-glucose" Nucleic Acids Sympo.Series.35. 15-16 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] E.Nozawa: "Synthesis and antitumor activity of 1-(3-C-ethynyl-b-D-ribo-pentfuranosyl)cytosine,-uracil and their surag modified derivatives" Nucleic Acids Sympo.Series. 35. 31-32 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Yoshimura: "Synthesis of iso-4′-thionucleosides using the Mitsunobu reaction" Nucleic Acids Sympo.Series. 35. 55-56 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Kakutani: "Activation of c-fos and c-jun Genes and Protease Association in Cell Death Induced with 5-Fluoro-2′-deoxyuridine in Mouse Mammary Tumor FM3A Cell Line" Nucleic Acids Symp.Ser.35. 269-270 (1996)

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      1996 Annual Research Report
  • [Publications] S.Kankawa: "The Endonuclase S Relative to dNTP Imbalance Death" Nucleic Acids Symp.Ser.35. 271-272 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Arai: "A Colourimetric DNA Diagnotic method for Falciparum Malaria and Vivax Malaria : a Field Trial in the Solomon Islands" Nucleosides Nucleotides. 15. 719-731 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Kimura: "Cases of Ovale Malaria and Malariae Malaria Successfully Treated with Mefloquine" Jpn.J.Trop.Med.Hyg.24. 171-175 (1996)

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      1996 Annual Research Report
  • [Publications] M.Miyake: "PCR Diagnosis of Malaria at Convalescent Stage Post-Treatment" J.Travel.Med.3. 119-121 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] T.Toyoda: "New Inhibitors based on Dihydrofolate Reductase Domain of Plasmodium falciparum" Biochem.Biophys.Res.Comm.(in press). (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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