Cycloheximide

Cycloheximide
Names
IUPAC name
4-[(2R)-2-[(1S,3S,5S)-3,5-Dimethyl-2-oxocyclohexyl]-2-hydroxyethyl]piperidine-2,6-dione
Other names
Naramycin A, hizarocin, actidione, actispray, kaken, U-4527
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.578
KEGG
RTECS number MA4375000
UNII
Properties
C15H23NO4
Molar mass 281.35 g·mol−1
Appearance Colorless crystals
Melting point 119.5 to 121 °C (247.1 to 249.8 °F; 392.6 to 394.1 K)
Hazards
Safety data sheet Oxford MSDS
Toxic (T)
R-phrases (outdated) R26 R27 R28
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Cycloheximide is a eukaryote protein synthesis inhibitor, produced by the bacterium Streptomyces griseus. Cycloheximide exerts its effect by interfering with the translocation step in protein synthesis (movement of two tRNA molecules and mRNA in relation to the ribosome), thus blocking translational elongation. Cycloheximide is widely used in biomedical research to inhibit protein synthesis in eukaryotic cells studied in vitro (i.e. outside of organisms). It is inexpensive and works rapidly. Its effects are rapidly reversed by simply removing it from the culture medium.[1]

Due to significant toxic side effects, including DNA damage, teratogenesis, and other reproductive effects (including birth defects and toxicity to sperm[2]), cycloheximide is generally used only in in vitro research applications, and is not suitable for human use as a therapeutic compound. Although it has been used as a fungicide in agricultural applications, this application is now decreasing as the health risks have become better understood.

Because cycloheximide is degraded by alkaline conditions (pH > 7), decontamination of work surfaces and containers can be achieved by washing with a non-harmful alkali solution such as soap.

It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.[3]

Discovery

Cycloheximide was reported in 1946 by Alma Joslyn Whiffen-Barksdale at the Upjohn Company.[4]

Experimental applications

Cycloheximide can be used as an experimental tool in molecular biology to determine the half-life of a protein. Treating cells with cycloheximide in a time-course experiment followed by Western blotting of the cell lysates for the protein of interest can show differences in protein half-life. Cycloheximide treatment provides the ability to observe the half-life of a protein without confounding contributions from transcription or translation.

It is used as a plant growth regulator to stimulate ethylene production. It is used as a rodenticide and other animal pesticide. It is also used in media to detect unwanted bacteria in beer fermentation by suppressing yeasts and molds growth in test medium.

The translational elongation freezing properties of cycloheximide are also used for ribosome profiling / translational profiling. Translation is halted via the addition of cycloheximide, and the DNA/RNA in the cell is then nuclease treated. The ribosome-bound parts of RNA can then be sequenced.

Cycloheximide has also been used for its antifungal properties to make isolation of bacteria from mixed samples easier.[5]

Spectrum of fungal susceptibility

Cycloheximide has been used to isolate dermatophytes and inhibit the growth of fungi in brewing test media. The following represents susceptibility data for a few commonly targeted fungi:[6]

Biological activity

Cycloheximide is a highly effective antibiotic with activity against mold, yeast, and phytopathogenic fungi, with lower activity against bacteria. It has been reported to inhibit the synthesis of both proteins and macromolecules, as well as affect apoptosis in eukaryotes. Inhibition of protein synthesis is believed to be mediated through RNA translation arrest, as demonstrated in rat thymocytes. Cycloheximide has also been reported to inhibit FKBP12 (peptidylprolylisomerase hFKBP12, PPIase hFKBP12) via competitive inhibition. Cycloheximide exerts its effect by interfering with the translocation step in protein synthesis (movement of two tRNA molecules and mRNA in relation to the ribosome) thus blocking translational elongation.[7]

See also

References

  1. ↑ Franz Müller, Peter Ackermann, Paul Margot (2012). "Fungicides, Agricultural, 2. Individual Fungicides". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.o12_o06.
  2. ↑ "TOXNET". toxnet.nlm.nih.gov.
  3. ↑ "40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities" (PDF) (July 1, 2008 ed.). Government Printing Office. Retrieved October 29, 2011.
  4. ↑ New York Botanical Gardens. "Alma Whiffen Barksdale Records (RG5)". nybg.org. Retrieved 1 March 2017.
  5. ↑ Sands, DC; Rovira AD. "Isolation of Fluorescent Pseudomonads with a Selective Medium". Applied Microbiology, 1970, Vol 20 No. 3, p513-514
  6. ↑ "Cycloheximide – The Antimicrobial Index Knowledgebase – TOKU-E". antibiotics.toku-e.com.
  7. ↑ "Cycloheximide-Naramycin A;Actidione-CAS 66-81-9 Buy Cycloheximide from supplier medchemexpress.com". MedchemExpress.com.
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