A new substance (Yoshixol) with an interesting antibiotic mechanism from wood oil of Japanese traditional tree (Kiso-Hinoki), Chamaecyparis obtusa

1. A neutral wood oil was extracted from Chamaecyparis obtusa (Kiso-Hinoki), which has been trusted nationally and preserved historically in the central part of Japan (Kiso, Nagano). 2. Hinokitiol, or thujaplicin (C10H12O2), which has been believed to exist in Cupressaceae, was not found in this neutral wood oil. Some differences between the extracting processes of the natural products are discussed. 3. A new chemical substance (Yoshixol, 4,4-dimethyl-6-methylene-2-cycrohexen-1-one) was simulated by several criteria (details in the text) as a major candidate of the neutral wood oil from Chamaecyparis obtusa. Thus, Yoshixol was newly synthesized. 4. The antibiotic effects of hinokitiol, the neutral wood oil and Yoshixol on methicillin-resistant Staphylococcus aureus (MRSA) were examined bacteriologically and morphologically. 5. All of the aforementioned three test materials showed complete antibiotic effects on MRSA by the bacteriological examination. However, the morphological findings showed entirely different aspects of cell death. 6. Hinokitiol caused an aggregative, degenerative and/or necrotic aspect, but the neutral wood oil and Yoshixol produced characteristic aspects: separation of contacted cells, blebbing, bugging-like eruption, formation of granules and an extensive reduction of individual cell size of MRSA. 7. Yoshixol was able to enhance those antibiotic effects on MRSA distinctly more than the neutral wood oil. 8. Yoshixol also showed a strong antibiotic effect on Escherichia coli, Mycobacterium chelonei, Pseudomonas aureginosa and Candida albicans. Morphological observations of those bacilli after Yoshixol revealed characteristic aspects of separation of contacted cells, bugging-like swelling, granulation, ballooning and reduction of cell size. 9. A possible mechanism of Yoshixol is discussed in regard to a molecular orbital theory on the basis of its electron orbits and to a thermodynamic interaction with the prokaryotic cell membrane. On the basis of the molecular properties of Yoshixol, future biological interests and possible biological effects of Yoshixol are suggested. (C) 1997 Elsevier Science Inc.