Inhibition of MMPs by alcohols

Arzu Tezvergil-Mutluay, Kelli A. Agee, Tomohiro Hoshika, Toshikazu Uchiyama, Leo Tjäderhane, Lorenzo Breschi, Annalisa Mazzoni, Jeremy M. Thompson, Courtney E. McCracken, Stephen Warwick Looney, Franklin Chi Meng Tay, David Henry Pashley

Research output: Contribution to journalArticle

27 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)926-933
Number of pages8
JournalDental Materials
Volume27
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • Alcohol
  • Collagen
  • Dentin matrix
  • HEMA
  • MMPs

ASJC Scopus subject areas

  • Materials Science(all)
  • Dentistry(all)
  • Mechanics of Materials

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    Tezvergil-Mutluay, A., Agee, K. A., Hoshika, T., Uchiyama, T., Tjäderhane, L., Breschi, L., Mazzoni, A., Thompson, J. M., McCracken, C. E., Looney, S. W., Tay, F. C. M., & Pashley, D. H. (2011). Inhibition of MMPs by alcohols. Dental Materials, 27(9), 926-933. https://doi.org/10.1016/j.dental.2011.05.004