Antiplatelet effect and selective binding to cyclooxygenase by molecular docking analysis of 3-alkylaminopropoxy-9,10-anthraquinone derivatives

作者：Gan Kim Hong; Teng Chi Huang; Lin Hsien Cheng; Chen Kun Tze; Chen Yu Chian^*; Hsu Mei Feng; Wang Jih Pyang; Teng Che Ming; Lin Chun Nan

来源：Biological & Pharmaceutical Bulletin, 2008, 31(8): 1547-1551.

DOI：10.1248/bpb.31.1547

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

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 mu M). 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)H, in the active site of COX-1.

• 出版日期2008-8
• 单位中国医科大学