Meiho University Institutional Repository:Item 987654321/4138
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    jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.meiho.edu.tw/ir/handle/987654321/4138


    题名: Novel Aporphine- and Proaporphine-Clerodane Hybrids Identifiedfrom the Barks of Taiwanese Polyalthia longifolia (Sonn.)Thwaites var. pendula with Strong Anti-DENV2 Activity
    作者: 林昀生
    贡献者: 健康暨護理學院
    关键词: Polyalthia longifolia var. pendula;clerodane;aporphine;proaporphine;anti-DENV2;NS2B-NS3 protease
    日期: 2023-08
    上传时间: 2023-08-30T06:05:12Z (UTC)
    摘要: Hybrid natural products produced via mixed biosynthetic pathways are unique andoften surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C-C or N-C covalent linkage. Here, we report four structurally attractive diterpene-alkaloid conjugates polyalongarins A-D (1-4), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula. Inaddition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed tode termine the chemical structures and stereo-configurations of 1. Compounds 1-4 were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of theNS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2activity with superb EC50 (2.8-6.4 uM) and CCso values (50.4-200 uM). The inhibitory mechanismof 1-4 on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of 1-4 and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane-
    aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors.
    显示于类别:[生物科技系] 期刊論文

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