title: Inhibition of MMPs by alcohols.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Department of Restorative Dentistry and Endodontics, University of Turku, School of Dentistry, Turku, Finland.
authors.forename: Arzu
authors.initials: A
authors.lastname: Tezvergil-Mutluay
authors.forename: Kelli A
authors.initials: KA
authors.lastname: Agee
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hoshika
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Leo
authors.initials: L
authors.lastname: Tjäderhane
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Breschi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mazzoni
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Courtney E
authors.initials: CE
authors.lastname: McCracken
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Looney
authors.forename: Franklin R
authors.initials: FR
authors.lastname: Tay
authors.forename: David H
authors.initials: DH
authors.lastname: Pashley
mesh_terms: D000293:Adolescent; D000438:Alcohols / Q000737:chemistry / Q000494:pharmacology*; D003804:Dentin / Q000201:enzymology*; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins; D012044:Regression Analysis; D012995:Solubility; D017001:Tooth Demineralization; D055815:Young Adult
chemical_list: D000438:Alcohols; D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D011994:Recombinant Proteins