ObjectivesMatrix 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.MethodsMolecular docking and network analysis were studied using AutoDock and Cytoscape software, respectively. Pharmacokinetic and toxicity characteristics of compounds were predicted using bioinformatics web tools.ResultsThe 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.ConclusionsThe 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.

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

Background: Matrix metalloproteinase-8 (MMP-8) is the most abundant member of the MMP family in human dentin. It takes a part in the normal physiology of tissue remodeling and wound healing, while the overexpression/hyperactivity of this protein leads to several oral disorders, including dental caries and peri-implant inflammation/diseases, and therefore, MMP-8 inhibition may have therapeutic effects. Accordingly, the current study aimed to identify potential MMP-8 inhibitors from cinnamic acid derivatives. Methods: The binding affinity of cinnamic acid and its several derivatives to the MMP-8 active site were estimated using the AutoDock 4.0 software. The pharmacokinetics, toxicity, and bioavailability of top-ranked MMP-8 inhibitors were also predicted by utilizing bioinformatics web tools. Results: Five of the studied components, including chlorogenic acid (CGA), caffeic acid 3-glucoside, rosmarinic acid, N-p-Coumaroyltyramine, and caffeic acid phenethyl ester (CAPE) demonstrated a salient affinity of binding to the MMP-8 catalytic site (∆Gbinding<-10 kcal/mol). It was estimated that these compounds can inhibit the MMP-8 at the nanomolar concentration, and therefore, were considered as top-ranked MMP-8 inhibitors. Finally, none of the top-ranked components revealed a considerable side effect and thus were found to be suitable for oral use. Conclusions: The results of the present study suggested that CGA, caffeic acid 3-glucoside, rosmarinic acid, N-p-coumaroyltyramine, and CAPE might have protective effects on tooth decay and peri-implant inflammation/diseases.