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

Abstract

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.

Molecular Docking, Tyrosinase, Collagenase, and Elastase Inhibition Activities of Argan By-Products

“…They reported docking scores ranging between −8 and −10 Kcal/mol. In another study published by Taherkhani et al (2020) [56], isoquercetin and epicatechin showed respective scores of −8.96 and −6.4 Kcal/mol. These data are in perfect agreement with the results here obtained for isoquercetin and epicatechin.…”

Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach

“…erefore, it is suggested that targeting ECM-related genes may result in therapeutic effects in patients with ameloblastoma, although this needs confirmation in the future. Several flavonoids have shown inhibitory effects on MMP13 and MMP8 in previous studies [45,46]. However, the binding affinity of these natural compounds should be examined on other ECM-related genes such as MMP14.…”

Identification of Potential Glucosyltransferase Inhibitors from Cinnamic Acid Derivatives Using Molecular Docking Analysis: A Bioinformatics Study

“…Tooth decay is one of the most common chronic diseases worldwide (32). It is a multifactorial disorder in which matrix metalloproteinases and S. mutans are most responsible for degrading the organic and mineral texture of the teeth, respectively (33,34). GTFase of S. mutans plays an essential role in biofilm formation, leading to more bacterial cohesion, acid production, and dental caries (11)(12)(13)35).…”

“…A pi-charge was detected between caffeic acid 3-glucoside and Asp588 (5.86 Å). It is worth mentioning that the π-π stack pairing, pi-charge, and salt bridges are the most stabilizing connections among ligands and proteins (33).…”