Antiplatelet Effect and Selective Binding to Cyclooxygenase by Molecular Docking Analysis of 3-Alkylaminopropoxy-9,10-anthraquinone Derivatives

• Gan Kim-Hong

  School of Pharmacy, Kaohsiung Medical University

• Teng Chi-Huang

  School of Pharmacy, Kaohsiung Medical University

• Lin Hsien-Cheng

  School of Technology for Medical Sciences, Kaohsiung Medical University

• Chen Kun-Tze

  Department of Biological Science and Technology, China Medical University

• Chen Yu-Chian

  Department of Biological Science and Technology, China Medical University

• Hsu Mei-Feng

  Department of Biochemistry, China Medical University

• Wang Jih-Pyang

  Department of Education and Research, Taichung Veterans General Hospital

• Teng Che-Ming

  Pharmacological Institute, College of Medicine, National Taiwan University

• Lin Chun-Nan

  School of Pharmacy, Kaohsiung Medical University Institute of Life Science, National Taitung University

Abstract

In an effort to develop potent cytotoxic inhibitors of cyclooxygenase (COX), a series of cytotoxic 3-alkylaminopropoxy-9,10-anthraquinone derivatives was screened to evaluate their antiplatelet effect on washed rabbit platelets and human platelet-rich plasma (PRP). Thrombin, arachidonic acid (AA), collagen, and platelet-activating factor (PAF) induced platelet aggregations were potently inhibited by compounds 1, 2, and 3 (each at 300 μM). Of the compounds tested in human PRP, compounds 1, 8, and 10 showed significant inhibition of primary and secondary aggregation induced by epinephrine and had a weak inhibitory effect on cyclooxygenase-1 (COX-1). Molecular docking studies revealed that compounds, 1, 8, and 10 were bound in the active sites of COX-1. This indicated that the antiplatelet effect of these three compounds was partially mediated through the suppression of COX-1 activity and reduced thromboxane formation. It is concluded that the cytotoxic compounds 1, 8, and 10 may interfere the conversion of arachidonic acid to prostaglandin (PG)H₂ in the active site of COX-1.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 31 (8), 1547-1551, 2008

  The Pharmaceutical Society of Japan

Keywords

• antiplatelet effect
• cyclooxygenase
• 3-alkylaminopropoxy-9,10-anthraquinone

Details

• CRID: 1390282679601537024
• NII Article ID: 110006839016
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.31.1547
• COI: 1:STN:280:DC%2BD1cvovF2itg%3D%3D
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 9587459
• PubMed: 18670087
• Web Site: http://id.ndl.go.jp/bib/9587459
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9587459
• Web Site: http://www.jstage.jst.go.jp/article/bpb/31/8/31_8_1547/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2008364724
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed