471-05-6

Basic information

• Product Name: zerumbone
• Synonyms: zerumbone;(2E,6E,10E)-2,6,9,9-Tetramethyl-2,6,10-cycloundecatrien-1-one;ZeruMbone (6CI,7CI);(2E,6E,10E)-2,6,9,9-tetramethylcycloundeca-2,6,10-trien-1-one;GIHNTRQPEMKFKO-SKTNYSRSSA-N
• CAS NO: 471-05-6
• Molecular Formula: C₁₅H₂₂O
• Molecular Weight: 218.33
• Mol File: 471-05-6.mol

Chemical Properties

• Melting Point: 67-69℃
• Boiling Point: 321.611 °C at 760 mmHg
• Flash Point: 133.945 °C
• Appearance: white to off-white/
• Density: 0.888 g/cm³
• Vapor Pressure: 0.000295mmHg at 25°C
• Refractive Index: 1.468
• Storage Temp.: 2-8°C
• Solubility: DMSO: ≥10mg/mL
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: zerumbone(CAS DataBase Reference)
• NIST Chemistry Reference: zerumbone(471-05-6)
• EPA Substance Registry System: zerumbone(471-05-6)

Safety Data

• Hazard Codes: Xi,N
• Statements: 43-50
• Safety Statements: 36/37-60-61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 471-05-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
Zerumbone is used as a potential therapeutic agent for the prevention and treatment of esophageal squamous cell carcinomas (ESCC). It has been investigated through liquid chromatography with mass spectrometry (LC-MS-MS) to assess its effectiveness in this application.
Used in Cancer Research:
Zerumbone is utilized as a compound that induces apoptosis in T-acute lymphoblastic leukemia cells. Importantly, it demonstrates no cytotoxic effects on normal cells, making it a promising candidate for targeted cancer therapies.
Used in Drug Delivery Systems:
Similar to gallotannin, zerumbone's potential applications and efficacy against cancer cells could be enhanced through the development of novel drug delivery systems. Utilizing various organic and metallic nanoparticles as carriers for zerumbone delivery may improve its bioavailability and therapeutic outcomes.

Biochem/physiol Actions

Zerumbone is a TRAIL-induced apoptosis potentiator. It potentiates TRAIL-induced apoptosis through the up-regulation of DR4 and DR5 expression and the down-regulation of cFLIP. Zerumbone has very little or no cytotoxic effect on the normal human endothelial cells and dermal fibroblasts. Zerumbone is a sesquiterpene isolated from in Zingiber zerumbet Smith (wild ginger).

Anticancer Research

Zerumbone is isolated from the rhizomes of the wild ginger Zingiber zerumbet. It isfound to suppress the proliferation of breast cancer and colon cancer cells and alsoto prevent initiation and promotion of skin cancer in mice. It also suppresses theNF-κB activation and its sequential suppression of IκBα kinase activity, IκBαphosphorylation, IκBα degradation, p65 phosphorylation, nuclear translocation,and acylation. It downregulates the NF-κB-regulated gene products like FLIP, cyclinD1, TRAF1, COX2, Bfl-1/A1, MMP-9, Bcl-xL, ICAM-1, Bcl-2, c-myc, XIAP,survivin, IAP1, and IAP2, and thus, it potentiates apoptosis (Murakami et al. 2002;Sakinah et al. 2007).

References

1) Leu et al. (2009), A small molecule inhibitor of inducible heat shock protein 70; Mol. Cell, 36 15 2) Abdelwahab et al. (2011), Zerumbone induces apoptosis in T-acute lymphoblastic leukemia cells; Leuk. Res., 35 268

InChI:InChI=1/C15H22O/c1-12-6-5-7-13(2)14(16)9-11-15(3,4)10-8-12/h7-9,11H,5-6,10H2,1-4H3/b11-9+,12-8+,13-7+

Upstream product

• 108101-44-6 (1S,2S)-1,2-epoxyhumulene 
• 17678-70-5 zerumbol 
• 17678-70-5 Zerumbol 
• 79729-85-4 (5E,9E)-(1S,11S)-1,5,8,8-Tetramethyl-12-oxa-bicyclo[9.1.0]dodeca-5,9-dien-2-one 
• 79729-84-3 (5E,9E)-(1R,2S,11S)-1,5,8,8-Tetramethyl-12-oxa-bicyclo[9.1.0]dodeca-5,9-dien-2-ol 
• 79729-83-2 (2Z,4E,8E)-(S)-2,6,6,9-Tetramethyl-cycloundeca-2,4,8-trienol 

Relevant articles and documents

Br?nsted acid-induced transannulation of the phytochemical zerumbone

The sesquiterpene zerumbone was treated with HCl in ethyl acetate under the light-protected condition, and the time-dependent conversions were analyzed by gas chromatography. Nine products were isolated, and their structures were revealed by several NMR m

A short-chain dehydrogenase involved in terpene metabolism from Zingiber zerumbet

The rhizome oil of Zingiber zerumbet Smith contains an exceptionally high content of sesquiterpenoids with zerumbone, a predominating potential multi-anticancer agent. Biosynthetic pathways of zerumbone have been proposed, and two genes ZSS1 and CYP71BA1 that encode the enzymes catalyzing the first two steps have been cloned. In this paper, we isolated a cDNA clone (ZSD1) that encodes an alcohol dehydrogenase capable of catalyzing the final step of zerumbone biosynthesis. ZSD1 has an open reading frame of 804 bp that encodes a 267-residue enzyme with a calculated molecular mass of 28.7 kDa. After expression in Escherichia coli, the recombinant enzyme was found to catalyze 8-hydroxy-α-humulene into zerumbone. ZSD1 is a member of the short-chain dehydrogenase/reductase superfamily (SDR) and shares high identities with other plant SDRs involved in secondary metabolism, stress responses and phytosteroid biosynthesis. In contrast to the transcripts of ZSS1 and CYP71BA1, which are almost exclusively expressed in rhizomes, ZSD1 transcripts are detected in leaves, stems and rhizomes, suggesting that ZSD1 may also be involved in other biological processes. Consistent with its proposed flexible substrate-binding pocket, ZSD1 also converts borneol to camphor with Km and k cat values of 22.8 μm and 4.1 s-1, displaying its bisubstrate feature.

The chemistry of zerumbone. Part 5: Structural transformation of the dimethylamine derivatives

Zerumbone (1) and its 6,7-epoxide (2) react with ammonia and dimethylamine regio- and stereospecifically, affording monoamines 3, 4, 7 and 8. All adducts have the same relative configuration at C2 and C3. The conjugate amination is thermodynamically controlled to arrive at a single diastereomer. At 15°C 7 reacts with cyanide to give aminonitrile 10 as the single product, while at 30°C, acyclic aminonitrile 11 is also formed. The reaction with 8 affords at 0°C bicyclic aminonitrile 12 of the asteriscane skeleton, while at 30°C or higher temperature, mixtures of 12 and tricyclic nitriles 13 and 13′ are obtained. Refluxing of 7, 8 and 10 in aqueous acetonitrile promotes scission of the zerumbone ring by retro-Mannich reaction to provide acyclic aldehydes 16-18, respectively. The dimethylamino group of 7, 8 and 10 is eliminated stereospecifically by Cope- and base-catalyzed eliminations to regenerate the zerumbone skeleton in the products 1, 2 and 21. Cope elimination of 12 results in a mixture of 13 and 13′ by deaminative transannular etherification.

CONVERSION OF HUMULENE TO ZERUMBONE

Humulene was first converted to zerumbone through a sequence of chemical reactions.