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    Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/50859

    Title: Coumarin-Purine Ribofuranoside Conjugates as New Agents against Hepatitis C Virus
    Authors: Hwu,JR;Lin,SY;Tsay,SC;De Clercq,E;Leyssen,P;Neyts,J
    Contributors: 化學學系
    Date: 2011
    Issue Date: 2012-03-27 18:11:33 (UTC+8)
    Publisher: 國立中央大學
    Abstract: About 3% of world's population is infected by the hepatitis C virus (HCV), for which prophylactic vaccine is not available yet. Nowadays, pegylated interferon-a and ribavirin are commonly used to treat HCV; unfortunately these drugs often produce significant side effects. Upon the desperate need of anti-HCV drugs, a plan to establish a new compound library was set that included leads with high antiviral activity, good hydrophilicity, yet low toxicity. Accordingly, 26 new conjugated compounds were synthesized through the chemical coupling of various 9-(beta-D-ribofuranosyl)purine-8-thiones with 3-(chloromethyl)coumarins bearing various substitucnts. A -SCH(2)- unit was used to link the coumarin and the purine moieties. The three hydroxyl groups at the 2'-, 3'-, and 5'-positions were selectively protected with an acyl or acetal group in these coumarin-purine ribofuranosides. Their anti-HCV and cytostatic determination assays were performed, and the structure activity relationship was established. Three conjugates in the family of 8-(coumarin-3'-yl)methylthio-9-(beta-D-ribofuranos-1 ''-yl)purine possessed an appealing ability to inhibit HCV replication with EC(50) between 5.5 and 6.6 mu M and EC(90) of similar to 20 mu M. These data in the new compound library provide clues for the future in the development of anti-HCV leads for viral eradication.
    Appears in Collections:[化學學系] 期刊論文

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