• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1989 Fiscal Year Final Research Report Summary

Search for antiviral agents based on the inhibition of viral specific enzymes

Research Project

Project/Area Number 63571044
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

INOUYE Yoshio  Hiroshima University School of Medicine, Associate Professor, 医学部, 助教授 (00136053)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Shoshiro  Hiroshima University School of Medicine, Professor, 医学部, 教授 (40013304)
Project Period (FY) 1988 – 1989
KeywordsReverse transcriptase / Retroviruses / Acquired immunodeficiency virus / Avian myeloblastosis virus / Streptonigrin / Quinone compounds / Polyoxometalates
Research Abstract

The inhibition of human immunodeficiency virus (HIV) reverse transcriptase by certain antibiotics and related compounds was studied in comparison with that of avian myeloblastosis virus (AMV) reverse transcriptase and cellular DNA polymerases. Antitumor antibiotic streptonigrin and synthetic quinone compounds were active against both HIV and AMV enzymes. MV enzyme was more sensitive than HIV enzyme to some antibiotics such as colistin and enduracidins A and B, whereas the streptonigrin alkyl esters inhibited HIV reverse transcriptase only. As for quinone compounds, we proposed the existence of a specific site of interaction, reffered to as a "quinone pocket", on AMV reverse transcriptase. This putative structure will be conserved on a wide range of reverse transcriptases, among which HIV enzyme is included. More than 100 quinone compounds, specially para- and iso-quinoline quinones, were synthesized to study the structure-activity correlationship. In general, ortho-quinoline quinones were found to be more active against AMV reverse transcriptase and less toxic toward mouse lymphoblastoma L5178Y cells, suggesting the superiority of the former to the latter as a specific inhibitor of replication of retroviruses.
Among heteropolyoxometalates, Keggin-type heteropolyoxotungstates represented by PM-19 K_7[PTi_2W_<10>O_<40>]-6H_2O proved to be potent inhibitors of HIV replication in vitro. HPA 23 has been known to be an inhibitor of reverse transcriptase. HPA 23 was applied to clinical cases for the first time in this group of compounds. However, the effect of HPA 23 on the the replication of HIV in vitro was negligible as compared to that of PM-19. The blocked viral adsorption to host cells is critical to the inhibition of HIV replication by PM-19.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 祝幸雄: "Mechanism of inhibition of reverse transcriptase by quinon antibiotics II.Dependence on putavtive quinone pocket on the enzyme molecule" J.Antibiotics. 41. 1474-1478 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武之令: "Comparative studies of the inhibitory properties of antibiotics on human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases and cellular DNA olymerases" J.Antibiotics. 42. 107-115 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中村昭四郎: "Reverse transciptase inhibitors" Novel Microbial Products for Medicine and Agriculture(Society for Industrial Microbiology). 91-99 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武之令: "Bilogical properties of streptonigrin derivatives III.In vitro and in vivo antiviral and antitumor activities" J.Antibiotics. 42. 968-976 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井上義雄: "Inhibition of avian myeloblastosis virus reverse transcriptase by flavones and isoflavones" J.Antibiotics. 42. 1523-1525 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井上義雄: "Inhibition of replication of human immunodeficiency virus by a heteropolyoxotungstate(PM-19)" Chem.Pharm.Bull.38. 285-287 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 武之令: "Novel in vitro anti-human immunodeficiency virus compounds:Keggin heteropolyoxotungstates."

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 井上義雄: "Inhibition of avian myeloblastosis virus reverse transcriptase by various quinone compounds:Structureactivity relationship"

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yukio Hafuri: "Mechanism of inhibition of reverse transcriptase by quinone antibiotics II. Dependence on putative quinone pocket on the enzyme molecule" J. Antibiotics. 41(10). 1471-1478 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yukinori Take: "Comparative studies of the inhibitory properties of antibiotics on human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases and cellular DNA" J. Antibiotics, 42(1), 107-115, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shoshiro Nakamura: "Reverse transcriptase inhibitors" Novel Microbial Products for Medicine and Agriculture (Society for Industrial Microbiology), 91-99, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yukinori Take: "Biological properties of streptonigrin derivatives III. In vitro and in vivo antiviral and antitumor activities" J. Antibiotics, 42(6), 968-976, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshio Inouye: "Inhibition of avian myeloblastosis virus reverse transcriptase by flavones and isoflavones" J. Antibiotics, 42(10), 1523-1525, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshio Inouye: "Inhibition of replication of human immunodeficiency virus by a heteropolyoxotungstate (PM-19)" Chem. Pharm. Bull. 38(1), 285-287, 1990.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yukinori Take: "Novel in vitro anti-human immunodeficiency virus compounds: Keggin heteropolyoxotungstates"

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshio Inouye: "Inhibition of avian myeloblastosis virus reverse transcriptase by various quinone compounds: Structure-activity relationship"

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1993-03-26  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi