Inhibitory effects of lignans on the activity of human matrix metalloproteinase 7 (Matrilysin)

Inhibitory effects of nine dibenzylbutyrolactone lignans on a human matrix metalloproteinase, matrilysin, were examined. All of the lignans examined inhibited matrilysin with the IC50 values ranging from 50 to >280 muM. Matairesinol, which has the basic structure of the other lignans, showed the weakest inhibition. Lignans with methylenedioxy ring(s) or a hydroxyl group at the C5-position inhibited matrilysin more strongly than matairesinol. 5-Hydroxypluviatolide, which has both a methylenedioxy ring and a hydroxyl group at the C5-position, was the most potent inhibitor (IC50 = 50 muM), suggesting that the introduction of these two elements might enhance synergistically the inhibitory activity of lignans. 5-Hydroxypluviatolide inhibited matrilysin in a competitive manner, and its inhibitory effect was greatly suppressed by the presence of another competitive inhibitor, dimethyl sulfoxide. The precursors of matairesinol, coniferyl alcohol and secoisolariciresinol, had no inhibitory activity, indicating that the dibenzylbutyrolactone structure is essential for the inhibition. It has been shown that lignans have the potential to inhibit matrilysin, and the knowledge of their structure-activity relationship might be beneficial to developing selective inhibitors for matrix metal loproteinases.