Molecular docking study of flavonoid compounds for possible matrix metalloproteinase-13 inhibition

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.

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.

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.

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.