Novel Aporphine- and Proaporphine-Clerodane Hybrids Identifiedfrom the Barks of Taiwanese Polyalthia longifolia (Sonn.)Thwaites var. pendula with Strong Anti-DENV2 Activity

MUIR > Graduate Institute of Health Care > Department of Biological Science and Technology > Papers > Item 987654321/4138

Please use this identifier to cite or link to this item: http://ir.meiho.edu.tw/ir/handle/987654321/4138

Title:	Novel Aporphine- and Proaporphine-Clerodane Hybrids Identifiedfrom the Barks of Taiwanese Polyalthia longifolia (Sonn.)Thwaites var. pendula with Strong Anti-DENV2 Activity
Authors:	林昀生
Contributors:	健康暨護理學院
Keywords:	Polyalthia longifolia var. pendula;clerodane;aporphine;proaporphine;anti-DENV2;NS2B-NS3 protease
Date:	2023-08
Issue Date:	2023-08-30T06:05:12Z (UTC)
Abstract:	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.
Appears in Collections:	[Department of Biological Science and Technology] Papers

Files in This Item:

File	Description	Size	Format
pharmaceuticals-15-01218.pdf		1958Kb	Adobe PDF	154	View/Open

View Licence

Loading...