Hamadan University of Medical Sciences Avicenna Journal of Dental Research 2423-7582 14 1 2022 03 29 Identification of Potential Anti-tooth-decay Compounds From Organic Cinnamic Acid Derivatives by Inhibiting Matrix Metalloproteinase-8: An In Silico Study 25 32 10.34172/ajdr.2022.05 EN Amir Taherkhani https://orcid.org/0000-0002-6546-8785 Athena Orangi https://orcid.org/0000-0003-0854-5868 Shirin Moradkhani https://orcid.org/0000-0002-5334-569X Alireza Jalalvand https://orcid.org/0000-0002-8863-5267 Zahra Khamverdi https://orcid.org/0000-0001-9623-5573 Journal Article 10.34172/ajdr.2022.05 2021 04 17 2021 10 13 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.