RESUMEN
Hinokitiol, the major component of Aomori Hiba (Thujopsis dolabrata Sieb. et Zucc. var. hondai M(AKINO)) has already been found to show strong antibacterial activity. In this study, its mechanism of action was examined using Escherichia coli IFO 3301 and Staphylococcus aureus IFO 12732. As a result, it was suggested that at least a part of the mechanism of the bactericidal action of hinokitiol was due to the metabolic inhibition of the cell membrane in connection with the permeability of the cell membrane and respiration from the following three points. Firstly, from examination of the portraits of electron micrograph of E. coli IFO 3301 and S. aureus IFO 12732, no morphological change was found in the group treated hinokitiol as compared with the control group. Secondly, the respiration of both bacteria was remarkably suppressed by the addition of hinokitiol. Thirdly, incorporation of [U-14C]-labeled adenine into low molecular and nucleic acid moiety of cell bodies of both bacteria was strongly inhibited by the addition of hinokitiol. Strong suppression was also found in the incorporation of [U-14C] -labeled amino acid mixtures into low molecular and protein moieties of cell bodies of both bacteria treated with hinokitiol.
Asunto(s)
Antiinfecciosos/farmacología , Escherichia coli/efectos de los fármacos , Monoterpenos/farmacología , Staphylococcus aureus/efectos de los fármacos , Tropolona/análogos & derivados , Adenina/metabolismo , Permeabilidad de la Membrana Celular/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Consumo de Oxígeno/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/metabolismo , Tropolona/farmacologíaRESUMEN
Five hinokitiol-related compounds (hinokitiol (beta-thujaplicin), beta-dolabrin, gamma-thujaplicin, 4-acetyltropolone and alpha -thujaplicin) isolated from the acid oil of Aomori Hiba (Thujopsis dolabrata Sieb. et Zucc. var hondai MAKINO) showed clear antifungal activity against wood-rotting fungi. These compounds have obvious insecticidal effects on termites. They also exhibited potent acaricidal activity against mites. The above-mentioned features suggest that Konjiki-do, a well known national treasure, one of the buildings in Chuson-ji Temple of Iwate Prefecture, Japan, which was built of wood from the tree containing these five compounds, was kept from harm against noxious insects and wood-rotting fungi for a long time of about 840 years, until it was extensively repaired in 1962. In addition to Konjiki-do, there are some old famous Buddhist temples and Shinto shrines using Aomori Hiba. From the results, it was found that Aomori Hiba (Hinokiasunaro) is excellent for use as building materials.
Asunto(s)
Budismo , Cupressaceae/química , Madera , Fungicidas Industriales/química , Fungicidas Industriales/aislamiento & purificación , Insecticidas/química , Insecticidas/aislamiento & purificación , Japón , Estructura Molecular , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Aceites de Plantas/aislamiento & purificación , Tropolona/análogos & derivados , Tropolona/química , Tropolona/aislamiento & purificaciónRESUMEN
Beta-dolabrin, gamma-thujaplicin, and 4-acetyltropolone, the components of Aomori Hiba (Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO), showed antifungal activity on seven kinds of plant-pathogenic fungi, antibacterial activity against two kinds of Legionella sp., and in vitro cytotoxic effect on murine P388 lymphocytic leukemia cell line. Firstly, beta-dolabrin, gamma-thujaplicin and 4-acetyltropolone had clear antifungal activity against seven kinds of plant-pathogenic fungi tested. In particular, beta-dolabrin and 4-acetyltropolone showed strong antifungal activity against Pythium aphanidermatum IFO 32440, with minimum inhibitory concentration (MIC) values of 6.0 microg/ml. Secondly, beta-dolabrin, gamma-thujaplicin and 4-acetyltropolone had obvious growth-inhibitory effect on two kinds of Legionella sp. 4-Acetyltropolone especially had strong antibacterial activity toward Legionella pneumophila SG 1, and its MIC value was 3.1 microg/ml. These three compounds showed cytotoxic effects against murine P388 lymphocytic leukemia cell line in vitro. The cytotoxic effect of three compounds in the murine P388 lymphocytic leukemia cell line were clear when cell growth was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. At 48 h after treatment, gamma-thujaplicin and 4-acetyltropolone at 0.63 microg/ml inhibited cell growth of murine P388 lymphocytic leukemia by 85% and 65%, respectively. At the same time after treatment, the growth of the murine P388 lymphocytic leukemia cell line was completely suppressed by the three compounds at concentrations higher than 5.0 microg/ml. Among these three compounds, gamma-thujaplicin had the strongest cytotoxic activity on the growth of this tumor cell line in vitro.
Asunto(s)
Cicloheptanos/farmacología , Monoterpenos/química , Monoterpenos/farmacología , Tropolona/análogos & derivados , Tropolona/química , Tropolona/farmacología , Animales , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Cicloheptanos/aislamiento & purificación , Hongos/efectos de los fármacos , Fungicidas Industriales/aislamiento & purificación , Fungicidas Industriales/farmacología , Legionella/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Monoterpenos/aislamiento & purificación , Plantas/microbiología , Thuja , Tropolona/aislamiento & purificaciónRESUMEN
alpha-Thujaplicin, a minor component of Aomori Hiba (Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO), showed rather strong antifungal activity against seven kinds of plant-pathogenic fungi, their minimum inhibitory concentrations (MICs) being in the range of 12.0-50.0 microg/ml. alpha-Thujaplicin and hinokitiol (the major component of Aomori Hiba) also showed clear antibacterial activity against Legionella pneumophila SG 1 and L. pneumophila SG 3, and their MICs are in the range of 6.25-50 microg/ml. This compound showed strong insecticidal activity against Reticulitermes speratus [50%-lethal concentration (LC(50)): 0.02 g/m(2)], and it also had clear acaricidal activity against Dermatophagoides farinae (LC(50): 0.66 g/m(2)). At 24 h after treatment, alpha-thujaplicin at 0.63 microg/ml inhibited the cell growth of murine P388 lymphocytic leukemia by 78%, and its cytotoxic activity at a concentration higher than 0.63 microg/ml was as high as that of vincristine, used as a positive control. On the other hand, the cytotoxic effect of alpha-thujaplicin at 0.63 microg/ml was weaker than that of vinblastine. In this respect, the strong cytotoxic effect of alpha-thujaplicin on murine P388 lymphocytic leukemia cell line should be emphasized, considering that it has recently been found to be low in toxicity to mice.
Asunto(s)
Monoterpenos/farmacología , Tropolona/análogos & derivados , Tropolona/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Leucemia P388 , Ratones , Monoterpenos/química , Estereoisomerismo , Tropolona/químicaRESUMEN
Tropolone (1). showed strong insecticidal activity on Tyrophagus putrescentiae and Dermatophagoides farinae. The insecticidal effect of 1 on both insects was stronger than that of hinokitiol (2, 4-isopropyltropolone: major component of Thujopsis dolabrata SIEB. et ZUCC. hondai MAKINO). The insecticidal activity of both compounds was higher than that of N,N-diethyl-m-toluamide (DEET), used as a positive control. Compound 1 had potent insecticidal activity against Coptotermes formosanus, although its activity was much lower than that of commercial chloropyrifos. Like 2, 1 showed the inhibitory activity toward metalloproteases such as carboxypeptidase A, collagenase and thermolysin and their inhibitory activities were much higher than that of 1,10-phenanthroline, used as a positive control. The inhibitory activity of 1 on carboxypeptidase A was especially high, its 50% inhibitory concentrations (IC(50)) being 2.73 x 10(-6) M. This inhibitory activity was as high as that of 2 (IC(50): 2.76 x 10(-6) M). Compound 1 inhibited the growth of seven kinds of plant-pathogenic fungi and their minimum inhibitory concentration (MIC) values were in the range of 6.0-50.0 microg/ml. In particular, 1 showed strong antifungal activity on Pythium aphanidermatum IFO-32440 (MIC: 6.0 microg/ml).
Asunto(s)
Antifúngicos/farmacología , Insecticidas/farmacología , Tropolona/farmacología , Animales , Antifúngicos/química , Insectos/efectos de los fármacos , Insectos/fisiología , Insecticidas/química , Pythium/efectos de los fármacos , Pythium/fisiología , Tropolona/químicaRESUMEN
4-Acetyltropolone, a minor component of Thujopsis dolabrata SIEB. et Zucc. hondai MAKINO, showed antimicrobial activity against various microorganisms including wood-rotting fungi, a phytogrowth-inhibitory effect with chlorophyll biosynthesis inhibition, cytotoxic effect and inhibitory activity on metalloproteases. This compound had strong antifungal activity on Daedalea dickinsii IFO-4979 [minimum inhibitory concentration (MIC): 0.2 microg/ml] and Coriolus versicolor IFO-4940 (MIC: 0.39 microg/ml). Its cytotoxic effect at 20.0/microg/ml on human stomach cancer KATO-III and Ehrich's ascites carcinoma was stronger than those of podophyllotoxin, vincristine and vinblastine, the anticancer agents isolated from higher plants and used clinically. This compound also had potent antibacterial activity against Staphylococcus epidermidis IFO-12993, its MIC being 1.56 microg/ml. However, other biological activities of 4-acetyltropolone were lower than those of hinokitiol which is the main component of this plant, suggesting that the contribution of the acetyl group at C-4 to biological activity is smaller than that of the isopropyl group at that position. The acute toxicity of 4-acetyltropolone (LD50: 335.2 mg/kg) to mice was much lower than that of hinokitiol (LD50: 191 mg/kg).