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) 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.
Objectives The new Coronavirus (SARS-CoV-2) created a pandemic in the world in late 2019 and early 2020. Unfortunately, despite the increasing prevalence of the disease, there is no effective drug for the treatment. A computational drug repurposing study would be an appropriate and rapid way to provide an effective drug in the treatment of the coronavirus disease of 2019 (COVID-19) pandemic. In this study, the inhibitory potential of more than 50 antiviral drugs on three important proteins of SARS-CoV-2, was investigated using the molecular docking method. Methods By literature review, three important proteins, including main protease, RNA-dependent RNA polymerase (RdRp), and spike, were selected as the drug targets. The three-dimensional (3D) structure of protease, spike, and RdRp proteins was obtained from the Protein Data Bank. Proteins were energy minimized. More than 50 antiviral drugs were considered as candidates for protein inhibition, and their 3D structure was obtained from Drug Bank. Molecular docking settings were defined using Autodock 4.2 software and the algorithm was executed. Results Based on the estimated binding energy of docking and hydrogen bond analysis and the position of drug binding, five drugs including, indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, had the highest inhibitory potential for all three proteins. Conclusions According to the results, among the mentioned drugs, saquinavir and lopinavir showed the highest inhibitory potential for all three proteins compared to the other drugs. This study suggests that saquinavir and lopinavir could be included in the laboratory phase studies as a two-drug treatment for SARS-CoV-2 inhibition.
ABSTRACT. The complex formation of anti-inflamatory drug piroxicam (PX, 4-hydroxy-2-methyl-N-2--pridyl-2H-1,2-benzothiazine-3-carboxadiamide-1,1-dioxide) with transition metal ions Co(II), Ni(II), Cu(II) and Zn(II) in methanol(MeOH)/water binary mixtures were studied by spectrophotometric method at 25 o C, constant pH = 5.0 and I = 0.1 M. The computer program SQUAD was used to extract the desired information from the spectral data. The outputs of the fitting processes were stability constants, standard deviations of the estimated stability constants, concentration distribution diagrams and spectral profiles of all species. The sequence of the stability constants of PX complexes with Co(II), Ni(II), Cu(II) and Zn(II) follow the Cu(II) > Co(II) > Ni(II) ≈ Zn(II) order. This may be due to different geometry tendencies of these metal ions. The acidity constants of the PX were also determined under above condition from its absorption spectra at different pH values. The computer program DATAN was used for determination of acidity constants of PX. The validity of the obtained acidity constants was checked by a well known computer program SPECFIT/32. The effects of the different parameters like solvent nature, cations characteristics on the stability and acidity constants were thoroughly discussed.
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