Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents

In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and d...

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Autores principales: Wang, Chao, Zhang, Hao, Xu, Fengrong, Niu, Yan, Wu, Yun, Wang, Xin, Peng, Yihong, Sun, Jing, Liang, Lei, Xu, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269873/
https://www.ncbi.nlm.nih.gov/pubmed/23698055
http://dx.doi.org/10.3390/molecules18056057
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author Wang, Chao
Zhang, Hao
Xu, Fengrong
Niu, Yan
Wu, Yun
Wang, Xin
Peng, Yihong
Sun, Jing
Liang, Lei
Xu, Ping
author_facet Wang, Chao
Zhang, Hao
Xu, Fengrong
Niu, Yan
Wu, Yun
Wang, Xin
Peng, Yihong
Sun, Jing
Liang, Lei
Xu, Ping
author_sort Wang, Chao
collection PubMed
description In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71) replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC(50) value of 54.57 nM in the MEK1 binding assay.
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spelling pubmed-62698732018-12-14 Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents Wang, Chao Zhang, Hao Xu, Fengrong Niu, Yan Wu, Yun Wang, Xin Peng, Yihong Sun, Jing Liang, Lei Xu, Ping Molecules Article In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71) replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC(50) value of 54.57 nM in the MEK1 binding assay. MDPI 2013-05-21 /pmc/articles/PMC6269873/ /pubmed/23698055 http://dx.doi.org/10.3390/molecules18056057 Text en © 2013 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 license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Wang, Chao
Zhang, Hao
Xu, Fengrong
Niu, Yan
Wu, Yun
Wang, Xin
Peng, Yihong
Sun, Jing
Liang, Lei
Xu, Ping
Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents
title Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents
title_full Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents
title_fullStr Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents
title_full_unstemmed Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents
title_short Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents
title_sort substituted 3-benzylcoumarins as allosteric mek1 inhibitors: design, synthesis and biological evaluation as antiviral agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269873/
https://www.ncbi.nlm.nih.gov/pubmed/23698055
http://dx.doi.org/10.3390/molecules18056057
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