Antimicrobial activity and metalloprotease inhibition of hinokitiol-related compounds, the constituents of Thujopsis dolabrata S. and Z-hondai MAK.

gamma-Thujaplicin, beta-dolabrin and hinakitiol(beta-thujaplicin), hinokiti ol-related compounds isolated from the wood of Thujopsis dolabrata S. and Z . hondai MAK have antimicrobial activity. In particular, strong antibacteri al activity of hinokitiol and beta-dolabrin on Staphylococcus epidermidis I FO-12993 was found, with a minimum inhibitory concentration (MIC) of 0.2 mu g/ml. This activity was higher than that of gentamicin, used as a positive control, and so the strong antibacterial activity of both compounds on thi s bacterium is of considerable interest. Of the three compounds, gamma-thuj aplicin showed the strongest antifungal activity and its MIC was found to b e around 1.5 mu g/ml. The three compounds also inhibited metalloproteases. The inhibitory activity of hinokitiol on carboxypeptidase A was especially strong, its 50%-inhibitory concentration (IC50) being 2.76 x 10(-6) M. Cons idering that metalloproteases are involved in inflammation, the strong inhi bitory activity of hinokitiol could be important. On the other hand, hinoki tiol-acetate did not show any antimicrobial activity and metalloprotease in hibition, suggesting that at least part of the activity is due to metal che lation between the carbonyl group at C-1 and the hydroxyl group at C-2 in t he tropolone skeleton.