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

2004 Fiscal Year Final Research Report Summary

Molecular design of anti-AIDS drugs targeting the viral and host zinc proteins

Research Project

Project/Area Number 15390038
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionKumamoto University

Principal Investigator

OTSUKA Masami  Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (40126008)

Co-Investigator(Kenkyū-buntansha) OKAMOTO Yoshinari  Kumamoto University, Faculty of Medical and Pharmaceutical Sciences, Research Associate, 大学院・医学薬学研究部, 助手 (20194409)
Project Period (FY) 2003 – 2004
KeywordsHIV / zinc protein / zinc complex / NFκB
Research Abstract

HIV RNA is reversetranscribed upon infection and subsequently integrated into the genome of the host cell. The provirus thus formed remains latent until certain stimuli activate the transcription of the integrated viral genes. Various viral and host proteins are involved in the transcription of viral genes and are regarded as significant, molecular targets for the treatment of AIDS.
In the present study, we are interested in integrase, HFκB, HIV-EP1, Sp1 and HIV Tat. All of them are zinc proteins or that closely related to zinc.
We have studied on the design and synthesis of zinc-binding artificial molecules containing a pyridine and two chelating side chains, aiming at the inhibition of the function of various zinc proteins. In 2003, we attempted the introduction of aromatic substituents onto the pyridine ring and examined hydroxamic acid in addition to cysteamine as the chelating side chains. We prepared pyridines bearing phenyl 2-tolyl, 3-tolyl, 4-tolyl, 3,5bis(trifluoromethyl)phenyl, 3,4-dimethoxyphenyl, 1-naphthyl,3-chlorophenyl substituents. A zinc chelator having 1-naphthyl group was found to be inhibitory against the farnesyltransferase, an important zinc protein in the signal transduction of Ras protein, with IC_<50> 1.9 μM. This compound induced morphological change in K-ras-NRK cells at.0.5 μg/ml and showed growth inhibition of K-ras-NRK cells with IC_<50> 0.32 μg/ml.
In 2004, the inhibitory effect of polyphenol carboxylic acids, such as aurintricarboxylic acid, gallic acid, and coumarin derivatives on the DNA binding of NFκB were studied. Evans blue was also found to be inhibitory against the DNA binding of NFκB. Molecular modeling studies suggest an explanation for the inhibition.
Thus, we are successful in the synthesis of novel compounds that inhibit function of zinc proteins related to AIDS.

  • Research Products

    (12 results)

All 2005 2004 2003

All Journal Article (12 results)

  • [Journal Article] Inhibitory activity of polyhydroxycarboxylate chelators against recombinant NF-κB p50 Protein-DNA binding2005

    • Author(s)
      Rakesh K.Sharma
    • Journal Title

      Bioorg.Chem 33(2)

      Pages: 67-81

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibitory activity of polyhydroxycarboxylate chelators against recombinant NF-κB p50 Protein-DNA binding2005

    • Author(s)
      Rakesh K.Sharma et al.
    • Journal Title

      Bioorg.Chem. 33(2)

      Pages: 67-81

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Evans Blue is an Inhibitor of Nuclear Factor kappa-B (NF-κB) DNA Binding2004

    • Author(s)
      Rakesh K.Sharma
    • Journal Title

      Bioorg.Med.Chem.Lett. 14(24)

      Pages: 6123-6127

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel Real-time Sensors to Quantitatively Assess In Vivo Inositol 1,4,5-Triphosphate Production in Intact Cells2004

    • Author(s)
      Kenji Sugimoto
    • Journal Title

      Chem.Biol. 11(4)

      Pages: 475-485

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Anthraquinone Polyamines : Novel Channel Blockers to Study NMDAReceptors2004

    • Author(s)
      Keiko Kashiwagi
    • Journal Title

      J.Pharmacol.Exp.Ther. 309(3)

      Pages: 884-893

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibitory Activities Against Topoisomerase I & II by Polyhydroxybenzoyl Amide Derivatives and their Structure-Activity Relationship2004

    • Author(s)
      Mohamed Abdel-Aziz
    • Journal Title

      Bioorg.Med.Chem.Lett. 14(7)

      Pages: 1669-1672

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Evans Blue is an Inhibitor of Nuclear Factor kappa-B(NF-κB)-DNA Binding2004

    • Author(s)
      Rakesh K.Sharma et al.
    • Journal Title

      Bioorg.Med.Chem.Lett. 14(24)

      Pages: 6123-6127

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel Real-time Sensors to Quantitatively Assess In Vivo Inositol 1,4,5-Triphosphate Production in Intact Cells2004

    • Author(s)
      Kenji Sugimoto et al.
    • Journal Title

      Chem.Biol. 11(4)

      Pages: 475-485

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Anthraquinone Polyamines : Novel Channel Blockers to Study NMDA Receptors2004

    • Author(s)
      Keiko Kashiwagi et al.
    • Journal Title

      J.Pharmacol.Exp.Ther. 309(3)

      Pages: 884-893

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibitory Activities Against Topoisomerase I & II by Poly-hydroxybenzoyl Amide Derivatives and their Structure-Activity Relationship2004

    • Author(s)
      Mohamed Abdel-Aziz et al.
    • Journal Title

      Bioorg.Med.Chem.Lett. 14(7)

      Pages: 1669-1672

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A Molecular Modeling Study of Inhibitors of Nuclear Factor Kappa-B (p50) - DNA Binding2003

    • Author(s)
      Vineet Pande
    • Journal Title

      J.Computer-Aided Molecular Design 17

      Pages: 825-836

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A Molecular Modeling Study of Inhibitors of Nuclear Factor Kappa-B(p50)-DNA Binding2003

    • Author(s)
      Vineet Pande et al.
    • Journal Title

      J,Computer-Aided Molecular Design 17

      Pages: 825-836

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

URL: 

Published: 2006-07-11  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi