Hinokitiol

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of β-thujaplicin
General
Surname Hinokitiol
other names
  • 2-Hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one
  • β-thujaplicin
  • HINOKITIOL ( INCI )
Molecular formula C 10 H 12 O 2
Brief description

white solid

External identifiers / databases
CAS number 499-44-5
EC number 207-880-7
ECHA InfoCard 100.007.165
PubChem 3611
ChemSpider 3485
Wikidata Q2705171
properties
Molar mass 164.20 g mol −1
Physical state

firmly

density

1.06 g cm −3

Melting point

50-52 ° C

boiling point

140 ° C (10 mmHg )

solubility

slightly soluble in water and benzene

safety instructions
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Hinokitiol ( β-thujaplicin ) is a natural monoterpenoid that occurs in the wood of trees belonging to the cypress family . Hinokitiol is used in oral care and treatment products because of its broad spectrum of antimicrobial and anti-inflammatory effects. It is also approved in Japan as a food additive for food preservation .

Chemically, hinokitiol belongs to the thujaplicine group and is structurally derived from 1,2-tropolone , from which it differs through an isopropyl substituent. Tropolones are known as chelating agents .

Hinoki cypress ( Chamaecyparis obtusa )

The name Hinokitiol is derived from the Taiwanese Hinoki false cypress ( Chamaecyparis obtusa var. Formosana ), from which it was first isolated in 1939. In fact, it is almost non-existent in Japanese Hinoki ( Ch. O. Var. Obtusa ), while it is present in high concentrations (about 0.04% of the heartwood mass) in Canary juniper (Juniperus cedrus) , Hiba arborvitae ( Thujopsis dolabrata ) and giant arborvitae ( Thuja plicata ) occurs. It can be easily extracted from cedar wood using organic solvents .

properties

A wide range of biological activities have been described in the literature. The first to be discovered and best known is the strong antimicrobial effect against many bacteria and fungi , regardless of antibiotic resistance. Hinokitiol has proven to be effective in vitro against Streptococcus pneumoniae , Streptococcus mutans and Staphylococcus aureus , common human pathogens. In addition, hinokitiol showed an inhibitory effect on Chlamydia trachomatis . An antiviral effect against human rhinoviruses , coxsackieviruses and mengoviruses results from its effect as a zinc ionophore . As such, it allows zinc ions to flow into cells, thereby inhibiting the replication machinery of RNA viruses and, as a result, virus replication. The study also provided evidence that hinokitiol inhibits picornavirus replication by interfering with the processing of the viral polyprotein , and that hinokitiol's antiviral activity is dependent on the availability of zinc ions. This mechanism is supported by research results with the chemically related zinc ionophore pyrithione .

In addition to broad spectrum antimicrobial activity, hinokitiol also has anti-inflammatory and anti - tumor activities, which have been described in a number of in vitro cell studies and in vivo animal studies. Hinokitiol inhibits key markers and pathways of inflammation, such as TNF-α and NF-κB , and the potential for the treatment of chronic inflammatory or autoimmune diseases is currently being investigated. Hinokitiol has been found to be cytotoxic to several known cancer cell lines by inducing autophagic processes .

use

Hinokitiol is used in a number of consumer products, including cosmetics , toothpaste , oral spray , sunscreen, and hair restorer . One of the leading brands is Hinoki Clinical from Hinoki Shinyaku, founded in 1956. Shortly before, in 1955, the industrial production of hinokitiol had started. Other cosmetic brands such as Relief Life (toothpaste) and others are sold by Japanese companies. Outside of Asia, companies like Swanson Vitamins are starting to use hinokitiol in consumer products in markets like the US and Australia.

On April 2, 2020, the Australian companies Advance Nanotek and AstiVita Limited applied for a patent for an antiviral composition containing hinokitiol for use in various oral care products ( DrZinx ).

history

discovery

Hinokitiol was discovered in 1936 by Tetsuo Nozoe in the Taiwan cypress essential oil . Compounds with a heptagonal molecular structure were previously considered not to occur in nature.

The main research interest of Nozoe, born in Sendai (Japan) in 1902 , who studied chemistry at Tohoku Imperial University and left Formosa (now known as Taiwan ) in 1926 , was the study of natural products, especially those from the Formosa region. Nozoe's documented work in Formosa was about the chemical constituents of Taiwanhinoki, a native conifer that grows in mountainous areas. Nozoe isolated a new compound from this species, the hinokitiol, and reported on it for the first time in 1936 in a special edition of the Bulletin of the Chemical Society of Japan .

When the Chemical Society of London organized a symposium entitled "Tropolone and Allied Compounds" in November 1950, Nozo's work on hinokitiol was recognized as an essential contribution to tropolone chemistry and helped his research gain recognition in the West. Thanks to JW Cook, chairman of the symposium, Nozoe was able to publish his work on hinokitiol and its derivatives in natural products in 1951. Nozoe's work, which began with the study of natural products in Taiwan and expanded in Japan in the 1950s and 60s, introduced a new field in organic chemistry, namely the chemistry of non-benzene aromatic compounds, which led Nozoe to 1958 at the age of 56 Imperial Order of Culture , the highest honor for contributing researchers and artists, was bestowed.

Younger research

From the 2000s onwards, researchers began to realize that hinokitiol could be of value as an antimicrobial agent, particularly for inhibiting the bacterium Chlamydia trachomatis .

The chemist Martin Burke and colleagues at the University of Illinois at Urbana-Champaign and other institutions discovered a special pharmacological property of hinokitiol in connection with iron transport in the animal organism. Disturbances in the iron metabolism can lead to an iron deficiency in cells ( anemia ) or the opposite effect, hemochromatosis . Using gene-depleted yeast cultures as a surrogate, the researchers examined a library of small biomolecules for signs of iron transport and thus for cell growth. Hinokitiol turned out to be what restored the cell's functionality. Further work by the team defined the mechanism by which hinokitiol restores or reduces iron in the cells. In a study on mammals, they found that rodents that were deficient in “iron proteins” resumed iron absorption in the intestine when they were fed hinokitiol. In a similar study on zebrafish, the molecule restored hemoglobin production. A comment on the work by Burke et al. gave Hinokitiol the nickname "Iron Man Molecule", which is ambiguous in that the first name of the discoverer Nozoe can be translated into English as "iron man".

Further research has been carried out on the application of hinokitiol to the oral cavity and upper respiratory tract in response to increased demand. One of the studies showed that hinokitiol has antibacterial activity against a wide range of pathogenic bacteria and is low in cytotoxicity to human epithelial cells.

Individual evidence

  1. ↑ Entry on HINOKITIOL in the CosIng database of the EU Commission, accessed on June 15, 2020.
  2. ↑ a b c d e f data sheet β-thujaplicin, 99% from Sigma-Aldrich , accessed on June 14, 2020 ( PDF ).
  3. ↑ a b David R. Lide: CRC Handbook of Chemistry and Physics A Ready-reference Book of Chemical and Physical Data . CRC Press, 1995, ISBN 978-0-8493-0595-5 , pp. 320 ( limited preview in Google Book search).
  4. ^ Effects of leaching on fungal growth and decay of western redcedar . In: Canadian Journal of Microbiology . tape 55 , no. 5 , May 2009, p. 578-86 , doi : 10.1139 / W08-161 , PMID 19483786 .
  5. ^ Tetsuo Nozoe: chemistry and life . In: Chemical Record . tape 12 , no. 6 , December 2012, p. 599-607 , doi : 10.1002 / tcr.201200024 , PMID 23242794 .
  6. ↑ Screening fungi tolerant to Western red cedar (Thuja plicata Donn) extractives. Part 1. Mild extraction by ultrasonication and quantification of extractives by reverse-phase HPLC . In: wood research . tape 61 , no. 2 , p. 190-194 , doi : 10.1515 / HF.2007.033 .
  7. ↑ In vitro antimicrobial and anticancer potential of hinokitiol against oral pathogens and oral cancer cell lines . In: Microbiological Research . tape 168 , no. 5 , June 2013, p. 254-62 , doi : 10.1016 / j.micres.2012.12.007 , PMID 23312825 .
  8. ↑ The mechanism of the bactericidal activity of hinokitiol . In: Biocontrol Science . tape 12 , no. 3 , September 2007, pp. 101-10 , doi : 10.4265 / bio.12.101 , PMID 17927050 .
  9. ^ Evaluation of the Antibacterial Potential of Liquid and Vapor Phase Phenolic Essential Oil Compounds against Oral Microorganisms . In: PLOS ONE . tape 11 , no. 9 , September 28, 2016, p. e0163147 , doi : 10.1371 / journal.pone.0163147 , PMID 27681039 .
  10. ↑ Antibacterial activity of hinokitiol against both antibiotic-resistant and -susceptible pathogenic bacteria that predominate in the oral cavity and upper airways . In: Microbiology and Immunology . tape 63 , no. 6 , June 2019, p. 213-222 , doi : 10.1111 / 1348-0421.12688 , PMID 31106894 .
  11. ↑ In vitro inhibitory effects of hinokitiol on proliferation of Chlamydia trachomatis . In: Antimicrobial Agents and Chemotherapy . tape 49 , no. 6 , June 2005, p. 2519-21 , doi : 10.1128 / AAC.49.6.2519-2521.2005 , PMID 15917561 .
  12. ↑ Russell Chedgy: Secondary metabolites of western red cedar (Thuja plicata): their biotechnological applications and role in conferring natural durability . Lambert Academic Publishing, Saarbrücken 2010, ISBN 978-3-8383-4661-8 (English).
  13. ↑ Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections . In: Journal of Virology . tape 83 , no. 1 , January 2009, p. 58-64 , doi : 10.1128 / JVI.01543-08 , PMID 18922875 .
  14. ↑ Zn (2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture . In: PLOS Pathogens . tape 6 , no. 11 , November 2010, p. e1001176 , doi : 10.1371 / journal.ppat.1001176 , PMID 21079686 .
  15. ↑ Can Hinokitiol Kill Cancer Cells? Alternative Therapeutic Anticancer Agent via Autophagy and Apoptosis . In: Korean Journal of Clinical Laboratory Science . tape 51 , no. 2 , June 30, 2019, p. 221–234 , doi : 10.15324 / kjcls.2019.51.2.221 .
  16. ↑ Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis . In: International Journal of Molecular Sciences . tape 19 , no. 4 , March 2018, p. 939 , doi : 10.3390 / ijms19040939 .
  17. ^ Hinoki Clinical History. Retrieved June 16, 2020 .
  18. ↑ Real Life Product Line. Retrieved June 16, 2020 .
  19. ^ Dental Series Product Page. Retrieved June 16, 2020 .
  20. ↑ Antioxidant Serum. Retrieved June 16, 2020 .
  21. ↑ Antioxidant Serum AU. Retrieved June 16, 2020 . }
  22. ↑ IP Australia: AusPat. Retrieved June 16, 2020 .
  23. ↑ Patent Upjahr AstiVita. Retrieved June 16, 2020 .
  24. ^ Zinc + hinokitiol. Retrieved June 16, 2020 .
  25. ↑ Hinokitiol Discovery. Retrieved June 16, 2020 .
  26. ↑ The Effect of Rice Husk Charcoal and Sintering Temperature on Porosity of Sintered Mixture of Clay and Zeolite . In: Indian Journal of Science and Technology . tape 11 , no. 8 , February 1, 2018, p. 1–12 , doi : 10.17485 / ijst / 2018 / v11i8 / 104310 .
  27. ↑ Tesuo Nozoe (1902-1996) . In: European Journal of Organic Chemistry . S. 899-928 .
  28. ↑ About the dyes in the wooden parts of the "Hinoki" tree. I. Hinokitin And Hinokitiol (Preliminary Notice) . In: Bulletin of the Chemical Society of Japan . tape 11 , no. 3 , March 1936, p. 295-298 , doi : 10.1246 / bcsj.11.295 .
  29. ^ Hinokitiol (β-Thujaplicin) from the Essential Oil of Hinoki [Chamaecyparis obtusa (Sieb. Et Zucc.) Endl.] In: Journal of Essential Oil Research . tape 10 , no. 6 , November 1998, pp. 711-712 , doi : 10.1080 / 10412905.1998.9701018 .
  30. ↑ substitution products of tropolones and allied compounds . In: Nature . tape 167 , no. 4261 , June 1951, p. 1055-7 , doi : 10.1038 / 1671055a0 , PMID 14843174 .
  31. ↑ Seth C. Rasmussen: Igniting the Chemical Ring of Fire. World Scientific Publishing, Singapore 2018, ISBN 978-1-78634-454-0 , doi : 10.1142 / 9781786344557_0012 (English).
  32. ^ Professor Tetsuo Nozoe and Taiwan . In: Chemical Record . tape 15 , no. 1 , February 2015, p. 373-82 , doi : 10.1002 / tcr.201402099 , PMID 25597491 .
  33. ↑ Hinokitiol. Retrieved June 16, 2020 .
  34. ↑ Anthony S. Grillo, Anna M. SantaMaria et al. a .: Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals. In: Science. 356, 2017, p. 608, DOI: 10.1126 / science.aah3862 . PMID 28495746 . PMC 5470741 (free full text).
  35. ^ Robert F. Service: Iron Man molecule restores balance to cells. Retrieved June 16, 2020 .
  36. ↑ Antibacterial activity of hinokitiol against both antibiotic-resistant and -susceptible pathogenic bacteria that predominate in the oral cavity and upper airways . In: Microbiology and Immunology . tape 63 , no. 6 , June 2019, p. 213-222 , doi : 10.1111 / 1348-0421.12688 , PMID 31106894 .