Actidione

Description

Cycloheximide is a glutarimide-type antibiotic produced by Streptomyces griseus. Colorless crystals, C15H23NO4 (281.4), melting point: 115.5–117 ?C, weak acidic substance (pKa 11.2), Soluble in chloroform, isopropanol and methanol; water > 21 g/L (2 ?C). Stable in pH 3–5, but rapidly destroyed in alkaline solutions.

Description

Cycloheximide is a glutarimide antibiotic produced by S. griseus that inhibits protein synthesis in eukaryotes (IC₅₀ = 5-50 μM) by interfering with translational elongation. Its effects on protein synthesis can either induce or inhibit apoptosis depending on cell type. Cycloheximide is widely used as a tool in molecular biology research for ribosome profiling and translational profiling as well as to determine the half-life of a protein.

Chemical properties

Off-white to light tan powder

Chemical properties

Cycloheximide is a colorless crystalline sub- stance.

The Uses of Actidione

immunomodulator

The Uses of Actidione

Cycloheximide is an antibiotic substance isolated from the beers of streptomycin-producing strains of Streptomyces griseus. Cycloheximide is used as fungicide.

The Uses of Actidione

Cycloheximide is the most recognised member of the glutarimide microbial metabolites. Cycloheximide was isolated from Streptomyces griseus in the late 1940s as a potent and broad spectrum antifungal. Cycloheximide inhibits protein synthesis by interfering with translocation. Cycloheximide is an established bioprobe and widely-used antifungal reagent in research with over 25,000 literature citations.

The Uses of Actidione

potent and selective 5-HT uptake inhibitor

The Uses of Actidione

immunosuppressant

What are the applications of Application

Cycloheximide is a highly effective antibiotic. It inhibits the synthesis of proteins and macromolecules.

Definition

ChEBI: Cycloheximide is a dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus. It has a role as a bacterial metabolite, a protein synthesis inhibitor, a neuroprotective agent, an anticoronaviral agent and a ferroptosis inhibitor. It is a member of piperidones, a piperidine antibiotic, an antibiotic fungicide, a dicarboximide, a secondary alcohol and a cyclic ketone. It is functionally related to a piperidine-2,6-dione.

General Description

Colorless crystals. Used as a fungicide and as a anticancer drug.

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.

Agricultural Uses

Fungicide; plant growth regulator: A U.S. EPA restricted Use Pesticide (RUP). Used as an antibiotic, plant growth regulator, and protein synthesis inhibitor. Inhibits growth of many plant pathogenic fungi. Effective for control of powdery mildew on roses and many other ornamentals, rusts and leaf spots on lawn grasses, and azalea petal blight. Also used as a repellent for rodents and other animal pests and in cancer therapy. Not listed for use in EU countries

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.

Potential Exposure

A potential danger to those involved in the manufacture, formulation, or application of this fun- gicide and pesticide. Used as an antibiotic, plant growth regulator, and protein synthesis inhibitor. Used on oranges for processing and to inhibit growth of many pathogenic plant fungi. Also used as a repellent for rodents and other animal pests; and in cancer therapy.

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].

First aid

If this chemical gets into the eyes, remove anycontact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts theskin, remove contaminated clothing and wash immediatelywith soap and water. Seek medical attention immediately. Ifthis chemical has been inhaled, remove from exposure,begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR ifheart action has stopped. Transfer promptly to a medicalfacility. When this chemical has been swallowed, get medical attention. Give large quantities of water and inducevomiting. Do not make an unconscious person vomit.Medical observation is recommended for 24-48 h following skin contact.

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.

storage

room temperature

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.

Incompatibilities

Incompatible with oxidizers, acid anhy- drides; strong bases.

Waste Disposal

High-temperature incinerator with flue gas scrubbing equipment.

References

1) Merck 14:2728