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

Synthesis and SQAR of DNA-Cleaving Propargylic Sulfones

Research Project

Project/Area Number 08044141
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field 工業物理化学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NISHIMOTO Sei-ichi  KYOTO UNIVERSITY Graduate School of Engineering, Professor, 工学研究科, 教授 (10115909)

Co-Investigator(Kenkyū-buntansha) DAI Wei-Min  Hong Kong Univ.Science & Technology, Chemistry, Associate Professor, 化学科, 助教授
ZHOU Ling  KYOTO UNIVERSITY Graduate School of Engineering, Assistant, 工学研究科, 助手 (50293890)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsDNA Cleavage / Propargylic Sulfones / Anti-tumor Compounds / Prodrug / Intercalation / Molecular Recognization / Cytotoxicity / Structure-Activity Relationship
Research Abstract

New class of propargylic sulfones, that are activated to possess alkylating reactivity toward a specific DNA-base sequence and thereby result in DNA-strand breaks, were designed and synthesized. The following results were obtained through the joint research for 2 years.
(1) The head investigator or the investigator of Kyoto University visited the Hong Kong University of Science and Technology, 2 times in 1996 and 3 times in 1997, investigating the molecular design and synthesis of propargylic sulfone compounds, and the structure-reactivity relationship of DNA-cleaving compounds including natural products.
(2) The investigator of the Hong Kong University of Science and Technology was invited once every year to investigate the research trends on the mechanism by which propargylic sulfones are activated to possess anti-tumor activity and cytotoxicity.
(3) 45 kinds of cis-enediyne type propargylic sulfones, mono-propargylic sulfones and bis-propargylic sulfones were synthesized to quantify th … More e structure-activity relationship on DNA cleavage and cytotoxicity. 1,5-Diyne compounds were identified to generate cis-enediyne structure by rearrangement of an allylic double bond.
(4) For a series of propargylic sulfone compounds, the DNA-cleaving activity was correlated to the intercalating ability to DNA double strand, indicating a trend that mono-propargylic sulfones cause DNA double-strand breaks more readily than bis-analogs. While napthalene and anthracene moieties are efficient function for DNA intercalation, effective DNA cleavage can not be achieved unless the active allenic sulfone moiety is located at the right sites for DNA base alkylation.
(5) A model reaction of propargylic sulfone with guanosine in aqueous solution demonstrated that the active allenic slufone moiety formed in situ alkylates the N7 position of guanosine, followed by hydrolytic release of ribose to give an adduct with guanine. This reaction pathway accounts for the DNA-cleaving activity of propargylic sulfones. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 戴 偉民: "Synthesis of cis-Enediynes from 1,5-Diynes by Rearrangement of an Allylic Double Bond" Angewandte Chemie International Edition in English. 35・7. 779-781 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 戴 偉民: "DNA Cleavage of Novel Propargylic Sulfones.Enhancement of Potency via Intercalating Interaction" Bioorganic & Medicinal Chemistry Letter. 6・10. 1093-1098 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 戴 偉民: "First Synthesis of cis-Enediynes from 1,5-Diynes by Rearrangement of an Allylic Double Bond." Tetrahedron Letters. 37. 8413-8416 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 西本 清一: "Hydroxyl Radical-Induced Cross-Linking of Thymine and Lysine:Identification of the Primary Structure and Mechanism" Bioorganic & Medicinal Chemistry Letter. 8(印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 戴 偉民: "Remarkable Tethering Effect on DNA Cleavage of Propargylic Sulfone Conjugates with Intercalating Moieties" Bioorganic & Medicinal Chemistry Letter. 8・2. 169-174 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dai, W.-M. ; Fong, K.C. ; Danjo, H. ; Nishimoto, S.: "Synthesis of cis-Enediynes from 1,5-Diynes by Rearrangement of an Allylic Double Bond" Angew.Chem.Int.Ed.Engl.35(7). 779-781 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dai, W.-M. ; Fong, K.C. ; Danjo, H. ; Nishimoto, S. ; Solow, M. ; Mak, W.L. ; Yeung, L.: "DNA Cleavage of Novel Propargylic Sulfones. Enhancement of Potency via Intercalating Interaction" BioMed.Chem.Lett.6(10). 1093-1098 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dai, W.-M.: "First Synthesis of cis-Enediynes from 1,5-Diynes by Rearrangement of an Allylic Double Bond." Tetrahedron Lrtt.37. 8413-8416 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morimoto, S. ; Hatta, H. ; Fujita, S. ; Matsuyama, T. ; Ueno, T. ; Nishimoto, S.: "Hydroxyl Radical-Induced Cross-Linking of Thymine and Lysine : Identification of the Primary Structure and Mechanism" BioMed.Chem.Lett.8 (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Dai, W.-M. ; Li, Q. ; Fong.K.C. ; Chow, C.W. ; Zhou, L. ; Nishimoto, S.: "Remarkable Tethering Effect on DNA Cleavage of Propargylic Sulfone Conjugates with Intercalating Moieties" BioMed.Chem.Lett.8(2). 169-174 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 西本 清一: "Hydroxyl Radical-Induced Cross-Linking of Thymine and Lysine:Identification of the Orimary Structure and Mechanism" Bioorganic & Medicinal Chemistry Letter. 8(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 戴 偉民: "Remarkable Tethering Effect on DNA Cleavage of Propargylic Sulfone Conjugates with Intercalating Moieties" Bioorganic & Medicinal Chemistry Letter. 8・2. 169-174 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 戴偉民: "Synthesis of cis-Endiynes from 1,5-Diynes by Rearrangement of an Allylic Double Bond" Angewandte Chemie International Edition in English. 35・7. 779-781 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 戴偉民: "DNA Cleavage of Novel Propargylic Sulfones.Enhancement of Potency via Intercalating Interaction" Bioorganic & Medicinal Chemistry Letters. 6・10. 1093-1098 (1996)

    • Related Report
      1996 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi