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Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy
Taking berberine (BBR) as the lead, 23 new BBR derivatives were synthesized and examined for their antiviral activities against four different genotype enterovirus 71 (EV71) strains with a cytopathic effect (CPE) assay. Structure-activity relationship (SAR) studies indicated that introduction of a s...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222558/ https://www.ncbi.nlm.nih.gov/pubmed/30127288 http://dx.doi.org/10.3390/molecules23082084 |
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author | Wang, Yan-Xiang Yang, Lu Wang, Hui-Qiang Zhao, Xiao-Qiang Liu, Ting Li, Ying-Hong Zeng, Qing-Xuan Li, Yu-Huan Song, Dan-Qing |
author_facet | Wang, Yan-Xiang Yang, Lu Wang, Hui-Qiang Zhao, Xiao-Qiang Liu, Ting Li, Ying-Hong Zeng, Qing-Xuan Li, Yu-Huan Song, Dan-Qing |
author_sort | Wang, Yan-Xiang |
collection | PubMed |
description | Taking berberine (BBR) as the lead, 23 new BBR derivatives were synthesized and examined for their antiviral activities against four different genotype enterovirus 71 (EV71) strains with a cytopathic effect (CPE) assay. Structure-activity relationship (SAR) studies indicated that introduction of a suitable substituent at the 9-position might be beneficial for potency. Among them, compound 2d exhibited most potent activities with IC(50) values of 7.12–14.8 μM, similar to that of BBR. The effect of 2d was further confirmed in a dose-dependent manner both in RNA and protein level. The mechanism revealed that 2d could inhibit the activation of MEK/ERK signaling pathway. Meanwhile, it could suppress the EV71-induced autophagy by activating AKT and inhibiting the phosphorylation of JNK and PI3KIII proteins. We consider BBR derivatives to be a new family of anti-EV71 agents through targeting host components, with an advantage of broad-spectrum anti-EV71 potency. |
format | Online Article Text |
id | pubmed-6222558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62225582018-11-13 Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy Wang, Yan-Xiang Yang, Lu Wang, Hui-Qiang Zhao, Xiao-Qiang Liu, Ting Li, Ying-Hong Zeng, Qing-Xuan Li, Yu-Huan Song, Dan-Qing Molecules Article Taking berberine (BBR) as the lead, 23 new BBR derivatives were synthesized and examined for their antiviral activities against four different genotype enterovirus 71 (EV71) strains with a cytopathic effect (CPE) assay. Structure-activity relationship (SAR) studies indicated that introduction of a suitable substituent at the 9-position might be beneficial for potency. Among them, compound 2d exhibited most potent activities with IC(50) values of 7.12–14.8 μM, similar to that of BBR. The effect of 2d was further confirmed in a dose-dependent manner both in RNA and protein level. The mechanism revealed that 2d could inhibit the activation of MEK/ERK signaling pathway. Meanwhile, it could suppress the EV71-induced autophagy by activating AKT and inhibiting the phosphorylation of JNK and PI3KIII proteins. We consider BBR derivatives to be a new family of anti-EV71 agents through targeting host components, with an advantage of broad-spectrum anti-EV71 potency. MDPI 2018-08-20 /pmc/articles/PMC6222558/ /pubmed/30127288 http://dx.doi.org/10.3390/molecules23082084 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Yan-Xiang Yang, Lu Wang, Hui-Qiang Zhao, Xiao-Qiang Liu, Ting Li, Ying-Hong Zeng, Qing-Xuan Li, Yu-Huan Song, Dan-Qing Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy |
title | Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy |
title_full | Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy |
title_fullStr | Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy |
title_full_unstemmed | Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy |
title_short | Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy |
title_sort | synthesis and evolution of berberine derivatives as a new class of antiviral agents against enterovirus 71 through the mek/erk pathway and autophagy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222558/ https://www.ncbi.nlm.nih.gov/pubmed/30127288 http://dx.doi.org/10.3390/molecules23082084 |
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