Affiliation:
1. Department of Oral and Maxillofacial Medicine , School of Dentistry, Hamadan University of Medical Sciences , Hamadan , Iran
2. Research Center for Molecular Medicine , Hamadan University of Medical Sciences , Hamadan , Iran
Abstract
Abstract
Objectives
Mitogen-activated protein kinase-3 (MAPK3) is the upstream regulator in the MAPK cascade and is involved in many critical signaling pathways and biological processes, such as cell proliferation, survival, and apoptosis. MAPK3 overexpression is linked to onset, development, metastasis, and drug resistance in several human cancers. Thus, identifying novel and effective MAPK3 inhibitors is highly demanded. Herein, we aimed to discover organic compounds from cinnamic acid derivatives as potential MAPK3 inhibitors.
Methods
The binding affinity of 20 cinnamic acids to the MAPK3 active site was tested using the AutoDock 4.0 software. Top-ranked cinnamic acids were ranked based on the ΔG
binding values between the ligands and the receptor’s active site. Interaction modes between top-ranked cinnamic acids and MAPK3 catalytic site were indicated using the Discovery Studio Visualizer tool. Molecular dynamics (MD) simulation was carried out to study the stability of the docked pose for the most potent MAPK3 inhibitor in this study.
Results
Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate exhibited a salient binding affinity to the MAPK3 active site with the criteria of ΔG
binding <−10 k cal/mol. Further, the inhibition constant value for cynarin was calculated at the picomolar concentration. The docked pose of cynarin within the MAPK3 catalytic domain was stable in 100 ns simulation.
Conclusions
Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate might be helpful in cancer therapy by inhibiting MAPK3.
Subject
Complementary and alternative medicine
Cited by
1 articles.
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