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

Biol Pharm Bull. 1999 Sep;22(9):990-3. doi: 10.1248/bpb.22.990.


Gamma-thujaplicin, beta-dolabrin and hinokitiol(beta-thujaplicin), hinokitiol-related compounds isolated from the wood of Thujopsis dolabrata S. and Z. hondai MAK have antimicrobial activity. In particular, strong antibacterial activity of hinokitiol and beta-dolabrin on Staphylococcus epidermidis IFO-12993 was found, with a minimum inhibitory concentration (MIC) of 0.2 microg/ml. This activity was higher than that of gentamicin, used as a positive control, and so the strong antibacterial activity of both compounds on this bacterium is of considerable interest. Of the three compounds, gamma-thujaplicin showed the strongest antifungal activity and its MIC was found to be around 1.5 microg/ml. The three compounds also inhibited metalloproteases. The inhibitory activity of hinokitiol on carboxypeptidase A was especially strong, its 50%-inhibitory concentration (IC50) being 2.76x10(-6) M. Considering that metalloproteases are involved in inflammation, the strong inhibitory activity of hinokitiol could be important. On the other hand, hinokitiol-acetate did not show any antimicrobial activity and metalloprotease inhibition, suggesting that at least part of the activity is due to metal chelation between the carbonyl group at C-1 and the hydroxyl group at C-2 in the tropolone skeleton.

MeSH terms

  • Anti-Bacterial Agents
  • Anti-Infective Agents / pharmacology*
  • Bacteria / drug effects
  • Carboxypeptidases / antagonists & inhibitors
  • Carboxypeptidases A
  • Cycadopsida / chemistry
  • Matrix Metalloproteinase Inhibitors
  • Metalloendopeptidases / antagonists & inhibitors*
  • Monoterpenes*
  • Penicillium / drug effects
  • Protease Inhibitors / pharmacology*
  • Thermolysin / antagonists & inhibitors
  • Tropolone / analogs & derivatives*
  • Tropolone / chemistry
  • Tropolone / pharmacology


  • 2-hydroxy-5-isopropyl- 2,4,6-cycloheptatrienone
  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Matrix Metalloproteinase Inhibitors
  • Monoterpenes
  • Protease Inhibitors
  • Tropolone
  • Carboxypeptidases
  • Carboxypeptidases A
  • Metalloendopeptidases
  • Thermolysin
  • beta-thujaplicin