Academic Journal
Novel Aporphine- and Proaporphine–Clerodane Hybrids Identified from the Barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula with Strong Anti-DENV2 Activity
| Title: | Novel Aporphine- and Proaporphine–Clerodane Hybrids Identified from the Barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula with Strong Anti-DENV2 Activity |
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| Authors: | I-Wen Lo, Geng-You Liao, Jin-Ching Lee, Chi-I Chang, Yang-Chang Wu, Yen-Yu Chen, Shang-Pin Liu, Huey-Jen Su, Chih-I Liu, Chia-Yi Kuo, Zheng-Yu Lin, Tsung-Lin Li, Yun-Sheng Lin, Chia-Ching Liaw |
| Source: | Pharmaceuticals, Vol 15, Iss 10, p 1218 (2022) |
| Publisher Information: | MDPI AG, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Medicine LCC:Pharmacy and materia medica |
| Subject Terms: | Polyalthia longifolia var. pendula, clerodane, aporphine, proaporphine, anti-DENV2, NS2B-NS3 protease, Medicine, Pharmacy and materia medica, RS1-441 |
| More Details: | Hybrid natural products produced via mixed biosynthetic pathways are unique and often 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. In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine 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 the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC50 (2.8–6.4 μM) and CC50 values (50.4–200 μM). The inhibitory mechanism of 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1424-8247 |
| Relation: | https://www.mdpi.com/1424-8247/15/10/1218; https://doaj.org/toc/1424-8247 |
| DOI: | 10.3390/ph15101218 |
| Access URL: | https://doaj.org/article/f14b68fe1d1e4f3198e43145edb49511 |
| Accession Number: | edsdoj.f14b68fe1d1e4f3198e43145edb49511 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 14248247 |
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| DOI: | 10.3390/ph15101218 |
| Published in: | Pharmaceuticals |
| Language: | English |