Abstract
Objectives
Matrix metalloproteinase-13 (MMP-13) has been reported to be involved in different biological processes such as degradation of extracellular matrix proteins, activating or degrading some significant regulatory proteins, wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization, ossification, cell migration, and tumor cell invasion. Further, MMP-13 participates in many oral diseases such as tooth decay, gingivitis, and degradation of enamel and tissue around the implant. In addition, inhibition of MMP-13 has shown therapeutic properties for Alzheimer’s disease (AD). We performed molecular docking to assess the binding affinity of 29 flavonoid compounds with the MMP-13. Additionally, pharmacokinetic and toxicity characteristics of the top-ranked flavonoids were studied. The current study also intended to identify the most important amino acids involved in the inhibition of MMP-13 based on topological feature (degree) in the ligand-amino acid network for MMP-13.
Methods
Molecular docking and network analysis were studied using AutoDock and Cytoscape software, respectively. Pharmacokinetic and toxicity characteristics of compounds were predicted using bioinformatics web tools.
Results
The results revealed that nine of the studied flavonoids had considerable estimated free energy of binding and inhibition constant: Rutin, nicotiflorin, orientin, vitexin, apigenin-7-glucoside, quercitrin, isoquercitrin, quercitrin-3-rhamnoside, and vicenin-2. Proline-242 was found to be the most important amino acid inhibiting the enzyme.
Conclusions
The results of the current study may be helpful in the prevention and therapeutic procedures of many disorders such as cancer, tooth caries, and AD. Nevertheless, validation tests are required in the future.
Acknowledgments
The authors would like to appreciate the Deputy of Research and Technology, Dental Research Center and Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan – Iran, for their supports.
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Research funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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Author contributions: AT, ZKH, and SHM designed the study. Energy minimization of the protein and small molecules was performed by AT and AO, respectively. Docking operations were conducted by AT. Molecular dynamics simulations were performed by AJ and AT. The ADME and toxicity studies were conducted by AT, ZKH, AO, SHM, and AJ. The network analysis was conducted and interpreted by AT. The results were analyzed and discussed by AT, ZKH, AO, SHM, and AJ. AT and SHM wrote the manuscript. All authors read and approved the final version of the manuscript.
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Competing interests: The authors declare that they have no competing interests.
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Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Ethics approval and consent to participate: The present study was approved by the Ethics Committee of Hamadan University of Medical Sciences, Hamadan, Iran (ethics no. IR.UMSHA.REC.1398.576).
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Consent for publication: Not applicable.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jbcpp-2020-0036).
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