Antimicrobial activity and metalloprotease inhibition of hinokitiol-related compounds, the constituents of Thujopsis dolabrata S. and Z. hondai MAK.
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.
Inamori
Y
Y
Osaka University of Pharmaceutical Sciences, Japan.
Shinohara
S
S
Tsujibo
H
H
Okabe
T
T
Morita
Y
Y
Sakagami
Y
Y
Kumeda
Y
Y
Ishida
N
N
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D043422:Carboxypeptidases A; D032462:Cycadopsida / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D039821:Monoterpenes; D010407:Penicillium / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology*; D013820:Thermolysin / Q000037:antagonists & inhibitors; D014334:Tropolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
C116333:2-hydroxy-5-isopropyl- 2,4,6-cycloheptatrienone; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D061965:Matrix Metalloproteinase Inhibitors; D039821:Monoterpenes; D011480:Protease Inhibitors; D014334:Tropolone; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D008666:Metalloendopeptidases; D013820:Thermolysin; C009479:beta-thujaplicin