Identification of Potential Anti-tooth-decay Compounds From Organic Cinnamic Acid Derivatives by Inhibiting Matrix Metalloproteinase-۸: An In Silico Study

Background: Matrix metalloproteinase-۸ (MMP-۸) is the most abundant member of the MMP family inhuman dentin. It takes a part in the normal physiology of tissue remodeling and wound healing, whilethe overexpression/hyperactivity of this protein leads to several oral disorders, including dental cariesand peri-implant inflammation/diseases, and therefore, MMP-۸ inhibition may have therapeutic effects.Accordingly, the current study aimed to identify potential MMP-۸ inhibitors from cinnamic acid derivatives.Methods: The binding affinity of cinnamic acid and its several derivatives to the MMP-۸ active site wereestimated using the AutoDock ۴.۰ software. The pharmacokinetics, toxicity, and bioavailability of toprankedMMP-۸ inhibitors were also predicted by utilizing bioinformatics web tools.Results: Five of the studied components, including chlorogenic acid (CGA), caffeic acid ۳-glucoside,rosmarinic acid, N-p-Coumaroyltyramine, and caffeic acid phenethyl ester (CAPE) demonstrated asalient affinity of binding to the MMP-۸ catalytic site (ΔGbinding < -۱۰ kcal/mol). It was estimated that thesecompounds can inhibit the MMP-۸ at the nanomolar concentration, and therefore, were considered astop-ranked MMP-۸ inhibitors. Finally, none of the top-ranked components revealed a considerable sideeffect and thus were found to be suitable for oral use.Conclusions: The results of the present study suggested that CGA, caffeic acid ۳-glucoside, rosmarinicacid, N-p-coumaroyltyramine, and CAPE might have protective effects on tooth decay and peri-implantinflammation/diseases.

Keywords:

Cinnamic acid , Inhibitor , Matrix metalloproteinase-۸ , Molecular docking , Tooth caries , Tooth decay