Inhibition of MMPs by alcohols

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 moles/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).

Dentin Bonding: Can We Make it Last?

“…1,5,6 Infiltration of hydrophobic monomers decreases water sorption and solubility and resin plasticization and may prevent or at least reduce enzymatic hydrolysis of collagen. [144][145][146][147] Together, these would lead to improved bond durability. 1,6 Currently, however, technique sensitivity and generally long treatment times prohibit ethanol-wet bonding in clinical settings, and more user-friendly and reproducible techniques or materials need to be developed for everyday use.…”

Effect of solvents on inhibition of collagen-bound proteases by chlorhexidine

“…The measurement of the loss of dry mass after 30-day incubation was used as an indirect measure of the proteases activity [25][26][27]. The dry mass of each beam was measured at the beginning and at the end of the 30-day incubation period.…”

“…Tezvergil-Mutluay et al [25] have shown that both soluble and dentine-matrix bound MMPs could be inhibited by alcohols; hence, the solvents used in the delivery of CHX during the dentine bonding procedure may be more crucial than that was thought. The solubility of CHX may also be different in different solvents.…”

Protocatechuate 3,4-Dioxygenase: A Wide Substrate Specificity Enzyme Isolated from <b><i>Stenotrophomonas maltophilia</i></b> KB2 as a Useful Tool in Aromatic Acid Biodegradation

“…The inhibitor may act as an allosteric one and interacts with the protein at a region different from the active site of the enzyme, or it may interact directly with the active site. Aliphatic alcohols are competitive inhibitors of metalloenzymes since they coordinate the metal ion in the enzyme's active site [Tezvergil-Multuay et al, 2011;Wójcik et al, 2011]. None of the studied aliphatic alcohols inhibited enzyme activity at any of the tested concentrations ( table 3 ).…”

“…Bertini et al [1994] observed a similar effect for catechol 2,3-dioxygenase. Methanol, as a lowmolecular alcohol, did not activate the examined enzyme due to its strong hydrogen interaction with the enzyme [Tezvergil-Multuay et al, 2011]. The enzyme with iron ion located in the active site of the enzyme can be inhibited by chelators [Gopalan et al, 1989].…”