Biological Activity of .ALPHA.-Thujaplicin, the Isomer of Hinokitiol

Abstract

In our previous paper, 1) antimicrobial activity, phytogrowth-inhibitory effect, cytotoxic activity and metalloprotease inhibition have been found as biological activities of athujaplicin (Chart 1), a minor component of Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO. At the same time, as the yield of a-thujaplicin was too small to permit examination of various biological activities, it was also reported to be chemically synthesized.1) As reported already, in addition to a-thujaplicin, hinokitiol-related compounds such as 4-acetyltropolone, hinokitiol (b-thujaplicin), b-dolabrin and g-thujaplicin have also been isolated from this plant. 2)As regards the biological activities of hinokitiol-related compounds, it has previously been reported by the authors that hinokitiol, b-dolabrin, g-thujaplicin and 4-acetyltropolone have antimicrobial activity, 1,3,4) metalloprotease inhibition, 1,3,4) cytotoxic effect, 1,4,5) phytogrowth-inhibitory activity 6,7) and an insecticidal effect. 8) However, no work has yet been done on other biological tests, except for the abovementioned activities of a-thujaplicin, because of its low yield.In this work, to determine the range of biological activity of hinokitiol-related compounds, the antifungal activity on plant-pathogenic fungi, antibacterial effect on Legionella species and acaricidal and insecticidal activities against Dermatophagoides farinae and Reticulitermes speratus of a-thujaplicin were investigated. The cytotoxic effect on the murine P388 lymphocytic leukemia cell line in vitro of a-thujaplicin was also examined. MATERIALS AND METHODSChemicals a-Thujaplicin, which was synthesized according to the method of the previous paper, 1) was used for various biological activities. Hinokitiol, isolated from T. dolabrata SIEB. et ZUCC. var. hondai MAKINO, was used for tests of insecticidal and acaricidal effects and antifungal activity on plant-pathogenic fungi as a comparative agent. N,NDiethyl-m-toluamide (DEET, a positive control for insecticidal activity testing on Dermatophagoides farinae) was obtained from Yoshitomi Pharmaceutical Industries, Ltd., Osaka, Japan. Chloropyrifos (a positive control for insecticidal activity testing on Reticulitermes speratus) was purchased from Hoechst Schering Agro Evo, Japan, Ltd., Osaka, Japan. Vinblastine and vincristine were also obtained from Sigma Chemical Co. (U.S.A. Sciences; 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan: c Aomori Industrial Research Center; 4-11-6 Daini-tonyamachi, Aomori 030-0113, Japan: d Japan: e Fumakilla Ltd.; Japan: f Osaka Municipal Technical Research Institute; Japan: and g The Sendai Institute of Microbiology; ICR Building 2F, ). At 24 h after treatment, a a-thujaplicin at 0.63 m mg/ml inhibited the cell growth of murine P388 lymphocytic leukemia by 78%, and its cytotoxic activity at a concentration higher than 0.63 m mg/ml was as high as that of vincristine, used as a positive control. On the other hand, the cytotoxic effect of a a-thujaplicin at 0.63 m mg/ml was weaker than that of vi...

The Antibacterial Activity of Fragrance Ingredients against Legionella pneumophila

“…10) Morita et al reported that hinokitiol and its related compounds exhibit high antibacterial activities against two strains of L. pneumophila. 6,7) The MIC for these compounds against the L. pneumophila strain SG 3 was assayed by the agar dilution method and was demonstrated to be in the range of 12.5 to 25.0 mg/ml. These values are similar to those for OM and BT (22.3 and 27.2 mg/ml, respectively) obtained in this study even though the actual method of MIC estimation differed.…”

“…Aliquots of 100 ml of the culture before (0 h, positive control) and after (1,3,6,12,24, 48 h) the addition of fragrance ingredient were used to estimate CFU on BYE-a plates with adequate dilution using buffered saline supplemented with 0.01% gelatin. Three plates were used for one sample and the estimation of CFU was repeated separately.…”

“…However, antibacterial activity against Legionella pneumophila, a causative agent of water-born, severe pneumonia has not been extensively investigated. [6][7][8] In our ongoing research into the antimicrobial activity of fragrance ingredients, we have established an improved method for the estimation of antimicrobial activity of volatile and hydrophobic fragrance ingredients. 9) Through this method, we have identified 101 of the 999 kinds of fragrance ingredients tested that demonstrate potent antimicrobial activity against representative strains of Gram-negative and Gram-positive bacteria and fungi.…”

Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

“…11 Hinokitiol is a natural component isolated from Chamaecyparis taiwanensis that exhibits antibacterial, antifungal, antiviral, antitumor, and insecticidal activities, with insignificant cytotoxicity. [12][13][14][15] Recent studies reported that Hinokitiol displayed a significant antiinflammatory activity in a series of cells through different mechanisms. 16,17 Owing to the intense research interest surrounding new therapies for DES and the previous promising activity of hinokitiol in inflammatory conditions, it is of great interest to assess whether hinokitiol can display an anti-inflammatory effect on the ocular surface.…”

Biological Activity of β-Dolabrin, γ-Thujaplicin, and 4-Acetyltropolone, Hinokitiol-Related Compounds

“…On the other hand, g-thujaplicin, a-thujaplicin, and 4-acetyltropolone, the minor components, were chemically synthesized [1][2][3] for various biological activity tests. It has been found by authors that these five compounds showed antimicrobial activity, [1][2][3][4] metalloprotease inhibition, [1][2][3][4] phytogrowth-inhibitory effects, 1,2,5) insecticidal activity, 4,6,7) and in vitro cytotoxic effect on human and murine tumor cell lines. 1,2,8,9) Among these five compounds, hinokitiol has also been used as a preservative for vegetabls, 10) flowers, 11) and mushrooms 12) as well as a plant growth stimulator 13) because of its strong antibacterial activity.…”