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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Detalles Bibliográficos
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
Descripción
Sumario: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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