Molecules 2013, 18(5), 6057-6091; doi:10.3390/molecules18056057
Article

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

1, 2, 1, 1,* email, 1, 2, 2, 1, 1 and 1,* email
Received: 25 April 2013; in revised form: 10 May 2013 / Accepted: 14 May 2013 / Published: 21 May 2013
(This article belongs to the Section Medicinal Chemistry)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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 IC50 value of 54.57 nM in the MEK1 binding assay.
Keywords: MEK1 inhibitor; coumarin; antiviral
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MDPI and ACS Style

Wang, C.; Zhang, H.; Xu, F.; Niu, Y.; Wu, Y.; Wang, X.; Peng, Y.; Sun, J.; Liang, L.; Xu, P. Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents. Molecules 2013, 18, 6057-6091.

AMA Style

Wang C, Zhang H, Xu F, Niu Y, Wu Y, Wang X, Peng Y, Sun J, Liang L, Xu P. Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents. Molecules. 2013; 18(5):6057-6091.

Chicago/Turabian Style

Wang, Chao; Zhang, Hao; Xu, Fengrong; Niu, Yan; Wu, Yun; Wang, Xin; Peng, Yihong; Sun, Jing; Liang, Lei; Xu, Ping. 2013. "Substituted 3-Benzylcoumarins as Allosteric MEK1 Inhibitors: Design, Synthesis and Biological Evaluation as Antiviral Agents." Molecules 18, no. 5: 6057-6091.

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