Literature DB >> 21676453

Inhibition of MMPs by alcohols.

Arzu Tezvergil-Mutluay1, Kelli A Agee, Tomohiro Hoshika, Toshikazu Uchiyama, Leo Tjäderhane, Lorenzo Breschi, Annalisa Mazzoni, Jeremy M Thompson, Courtney E McCracken, Stephen W Looney, Franklin R Tay, David H Pashley.   

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 IC(50)).
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).
Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

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Year:  2011        PMID: 21676453      PMCID: PMC3152585          DOI: 10.1016/j.dental.2011.05.004

Source DB:  PubMed          Journal:  Dent Mater        ISSN: 0109-5641            Impact factor:   5.304


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