66-81-9

Basic information

• Product Name: Actidione
• Synonyms: Cycloheximide solution,CHX;Cycloheximide 100mg [66-81-9];Cycloheximide Solution 100ug/ml in Acetonitrile;CYCLOHEXIMIDE READY MADE;CyclohexiMide(CHX),Actidione;4-[(2R)-2-[(1S,3S,5S)-3,5-DiMethyl-2-oxocyclohexyl]-2-hydroxyethyl]-2,6-piperidinedione;FT 3422-2;NaraMycin Microcapsule D 80
• CAS NO: 66-81-9
• Molecular Formula: C15H23NO4
• Molecular Weight: 281.34742
• EINECS: 200-636-0
• Product Categories: Amines, Chiral Reagents, Heterocycles, Pharmaceuticals, Intermediates & Fine Chemicals;ERGAMISOL;antibiotic;Miscellaneous;Antibiotic Explorer;Antifungal;Signalling;Antibiotics
• Mol File: 66-81-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 111-116 °C
• Boiling Point: 492℃
• Flash Point: 87°0°(230°F)
• Appearance: White/Glassy Irregular Shaped Granules
• Density: 1.0867 (rough estimate)
• Vapor Pressure: 9.81E-12mmHg at 25°C
• Refractive Index: 1.5000 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Soluble in Ethanol (up to 14 mg/ml) or in Water (up to 7 mg/ml).
• PKA: 11.61±0.40(Predicted)
• Water Solubility: 2.1 g/100 mL (2 ºC)
• Stability: Stable. Combustible. Incompatible with strong oxidizing agents, acid chlorides, acid anhydrides, alkali.
• BRN: 88868
• CAS DataBase Reference: Actidione(CAS DataBase Reference)
• NIST Chemistry Reference: Actidione(66-81-9)
• EPA Substance Registry System: Actidione(66-81-9)

Safety Data

• Hazard Codes: Xn,T,N,T+
• Statements: 22-68-61-51/53-28-38-52/53
• Safety Statements: 53-45-61-36/37-28
• RIDADR: UN 2811 6.1/PG 1
• WGK Germany: 3
• RTECS: MA4375000
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 66-81-9(Hazardous Substances Data)

Usage

Description

Actidione, also known as Cycloheximide, is a glutarimide-type antibiotic produced by Streptomyces griseus. It is a colorless crystalline substance with the chemical formula C15H23NO4 and a molecular weight of 281.4. Actidione is a weakly acidic compound with a pKa value of 11.2 and is soluble in chloroform, isopropanol, and methanol, as well as in water at concentrations greater than 21 g/L at 2°C. It is stable in acidic pH conditions (3-5) but is rapidly destroyed in alkaline solutions.

Uses

Used in Molecular Biology Research:
Actidione is used as a tool in molecular biology research for ribosome profiling and translational profiling, as well as to determine the half-life of proteins. It inhibits protein synthesis in eukaryotes by interfering with translational elongation, which can either induce or inhibit apoptosis depending on the cell type.
Used in Pharmaceutical Industry:
Actidione is used as an immunomodulator in the pharmaceutical industry, helping to modulate the immune response in various conditions.
Used in Agriculture:
Actidione is used as a fungicide in agriculture, specifically as an antifungal agent to protect crops from fungal infections. It is a potent and broad-spectrum antifungal that inhibits protein synthesis by interfering with translocation.
Used in Neuropharmacology:
Actidione is used as a potent and selective 5-HT (serotonin) uptake inhibitor in neuropharmacology research, helping to study the role of serotonin in various neurological and psychiatric disorders.

Air & Water Reactions

Water soluble.

Reactivity Profile

Actidione is an imide. Actidione is incompatible with strong oxidizing agents, acid chlorides and acid anhydrides. Actidione decomposes rapidly in alkali at room temperature.

Health Hazard

Actidione is extremely toxic; the probable oral lethal dose in humans is 5-50 mg/kg, or 7 drops to 1 teaspoonful for a 150-lb. person.

Fire Hazard

When exposed to heat, Actidione emits toxic fumes, including nitrogen oxides.

Trade name

ACTI-AID?[C]; ACTIDIONE?[C]; ACTIDIONE? TGF[C]; ACTIDONE?; ACTIDONE? PM; ACTIDONE? TGF; ACTISPRAY; HIZAROCIN?; KAKEN?; NARAMYCIN?; NARAMYCIN A?; NEOCYCLOHEXIMIDE?; U-4527

Biological Activity

Selective inhibitor of eukaryotic (over prokaryotic) protein synthesis, blocking tRNA binding and release from ribosomes. Induces apoptosis in a variety of transformed and normal cell lines, including T-cells. Competitively inhibits the PPIase hFKBP12 (K i = 3.4 μ M). Antifungal antibiotic.

Pharmacology

Strongly inhibits the growth of pathogenic fungi but no effects on bacterial growth, even at 100 mg/ml. Inhibits protein synthesis by interfering with the translocation step in eukaryotes, but not in prokaryotes. When ingested by animals, the agent causes excitement, tremors, salivation, diarrhea, and melena.

in vitro

cycloheximide blocks the movement of peptidyl-trna from acceptor site to the donor site on reticulocyte ribosomes. this translocation reaction is dependent on the transfer enzyme, tf-ii, and gtp hydrolysis. cycloheximide has no effect on the ribosome dependent gtpase activity of tf-ii or peptidyl transferase reaction by which peptides on trna in the donor ribosomal site are transferred to an amino acid on trna in the acceptor site [1].

in vivo

cycloheximide treatment was effective in attenuating rat brain injury within a 6 hr therapeutic window after hypoxia-ischemia in a newborn rat pup model. these data support the possibility that protein synthesis inhibitors, as well as other anti-apoptotic strategies, may have therapeutic utility in hypoxic-ischemic (hi) events of the developing newborn brain even when treatment is delayed for up to 6 hr after the primary asphyxial insult [2].

Carcinogenicity

Cycloheximide is genotoxic in Escherichia coli with metabolic activation and in the mouse sperm morphology assay. Carcinogenicity bioassays in the mouse and rat are inconclusive.

Environmental Fate

CHX is a potent inhibitor of protein synthesis in animals. It binds to E-site of 70S ribosome-mRNA complex, blocking the translational step of protein biosynthesis. It causes an increase in adrenal RNA and increased production of glucocorticoids.

Metabolism

Rapidly inactivated at room temperature by diluted alkali with the formation of a volatile, fragrant ketone, 2,4- dimethylcyclohexanone. Hazardous to fish and wildlife.

Purification Methods

It crystallises from H2O /MeOH (4:1), amyl acetate, isopropyl acetate/isopropyl ether or H2O. [Beilstein 21/13 V 434.]

Toxicity evaluation

Skin irritant. LD50 2 mg/kg (rat, orl); 133 mg/kg (mice, Ipr); 65 mg/kg (guinea pig); 60 mg/kg (monkey). Teratogenic effects.To remove toxicant from gut, activated charcoal and a catharitic dose of sodium sulfate are effective. Mechanisms of toxicity are not well defined, but hydrocortisone is antidotal, particularly in combination with the adrenergic agent methoxyphenamine.

References

1) Merck 14:2728

InChI:InChI=1/C15H23NO4/c1-8-3-9(2)15(20)11(4-8)12(17)5-10-6-13(18)16-14(19)7-10/h8-12,17H,3-7H2,1-2H3,(H,16,18,19)/t8-,9-,11-,12+/m0/s1

Upstream product

• 3428-71-5 C₁₆H₂₆N₄O₄ 
• 2066-88-8 (2,6-dioxo-piperidin-4-yl)-acetaldehyde 
• 93921-42-7 (+)-(2S,4R)-trans-2,4-dimethyl-1-cyclohexanone 
• 1001-75-8 4-methyl-4-pentenoic acid 
• 1149347-46-5 3-[(dodecylthio-carbonyl)-methyl]-glutarimide 
• 1154-58-1 dehydrocycloheximide 

Downstream Products

• 94130-63-9 (2S,4S,6R,αS)-cycloheximide 
• 66-81-9 (2S,4S,6S,αS)-cycloheximide 
• 642-81-9 Cycloheximide 
• 523-86-4 streptovitacin A 
• 69256-18-4 (-)-(2R,4R)-cis-2,4-Dimethyl-1-cyclohexanone 
• 100201-04-5 5-(2-Methylamino-4-nitro-phenoxy)-pentanoic acid (R)-1-((1S,3S,5S)-3,5-dimethyl-2-oxo-cyclohexyl)-2-(2,6-dioxo-piperidin-4-yl)-ethyl ester 
• 6746-42-5 (+)-(2R,4S,6R,αR)-Isocycloheximide 
• 526-02-3 3-[2-(2-hyroxy-3,5-dimethylphenyl)-2-oxoethyl] glutarimide 
• 102598-39-0 3-(2-benzylimino-ethyl)-glutaric acid amide-benzylamide 
• 246257-13-6 {4-[(R)-2-((1S,3S,5S)-3,5-Dimethyl-2-oxo-cyclohexyl)-2-hydroxy-ethyl]-2,6-dioxo-piperidin-1-yl}-acetic acid ethyl ester 

Relevant articles and documents

Versatile Synthetic Route to Cycloheximide and Analogues That Potently Inhibit Translation Elongation

Cycloheximide (CHX) is an inhibitor of eukaryotic translation elongation that has played an essential role in the study of protein synthesis. Despite its ubiquity, few studies have been directed towards accessing synthetic CHX derivatives, even though such efforts may lead to protein synthesis inhibitors with improved or alternate properties. Described here is the total synthesis of CHX and analogues, and the establishment of structure–activity relationships (SAR) responsible for translation inhibition. The SAR studies aided the design of more potent compounds, one of which irreversibly blocks ribosomal elongation, preserves polysome profiles, and may be a broadly useful tool for investigating protein synthesis.

KINETICALLY AND THERMODYNAMICALLY CONTROLLED SYNTHESIS OF 2,6-DISUBSTITUTED CYCLOHEXANONE SEMICARBAZONES. A MOLECULAR MECHANICS STUDY OF A1,3-STRAIN

Reasonable values for Me-Me, H-Me and Me-H A1,3-strain have been evaluated by molecular mechanics calculations on differently substituted methylenecyclohexanes (5.46-6.75, 1.03 and 0.71 kcal/mol, respectively).The chair-to-chair inversion barri

Cycloheximide transformations. I. Kinetics and mechanisms in aqueous acid.

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