Inhibition of MMPs by alcohols

• Published in: Dental materials 2011-09, Vol.27 (9), p.926-933
• Main Authors: Tezvergil-Mutluay, Arzu, Agee, Kelli A, Hoshika, Tomohiro, Uchiyama, Toshikazu, Tjäderhane, Leo, Breschi, Lorenzo, Mazzoni, Annalisa, Thompson, Jeremy M, McCracken, Courtney E, Looney, Stephen W, Tay, Franklin R, Pashley, David H
• Format: Article
• Language: English
• Subjects: Adolescent; Advanced Basic Science; Alcohol; Alcohols; Alcohols - chemistry; Alcohols - pharmacology; Collagen; Dentin; Dentin - enzymology; Dentin matrix; Dentistry; Dipeptides - pharmacology; Dose-Response Relationship, Drug; Ethanol; Ethyl alcohol; HEMA; Humans; Hydrophobic and Hydrophilic Interactions; Inhibition; Inhibitors; Inhibitory Concentration 50; Matrix Metalloproteinase Inhibitors; Methyl alcohol; Methylene; MMPs; Protease Inhibitors - pharmacology; Recombinant Proteins; Regression Analysis; Solubility; Tooth Demineralization; Young Adult
• ISSN: 0109-5641; 1879-0097
• DOI: 10.1016/j.dental.2011.05.004

Abstract Objectives While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols. Methods The possible inhibitory activity of a series of alcohols was measured against soluble rhMMP-9 and insoluble matrix-bound endogenous MMPs of dentin in completely demineralized dentin. Increasing concentrations (0.17, 0.86, 1.71 and 4.28 mol/L) of a homologous series of alcohols (i.e. methanol, ethanol, propanols, butanols, pentanols, hexanols, the ethanol ester of methacrylic acid, heptanols and octanol) were compared to ethanediol, and propanediol by regression analysis to calculate the molar concentration required to inhibit MMPs by 50% (i.e. the IC50 ). Results Using two different MMP models, alcohols were shown to inhibit rhMMP-9 and the endogenous proteases of dentin matrix in a dose-dependent manner. The degree of MMP inhibition by alcohols increased with chain length up to 4 methylene groups. Based on the molar concentration required to inhibit rhMMP-9 fifty percent, 2-hydroxyethylmethacrylate (HEMA), 3-hexanol, 3-heptanol and 1-octanol gave the strongest inhibition. Significance The results indicate that alcohols with 4 methylene groups inhibit MMPs more effectively than methanol or ethanol. MMP inhibition was inversely related to the Hoy's solubility parameter for hydrogen bonding forces of the alcohols (i.e. to their hydrophilicity).