Menadione

Menadione[1]
Names
IUPAC name
2-Methylnaphthalene-1,4-dione
Other names
Menaphthone; Vitamin K3; β-Methyl-1,4-naphthoquinone; 2-Methyl-1,4-naphthodione; 2-Methyl-1,4-naphthoquinone
Identifiers
58-27-5 YesY
ChEBI CHEBI:28869 N
ChEMBL ChEMBL590 YesY
ChemSpider 3915 YesY
DrugBank DB00170 N
Jmol interactive 3D Image
KEGG D02335 YesY
PubChem 4055
UNII 723JX6CXY5 YesY
Properties
C11H8O2
Molar mass 172.18 g·mol−1
Appearance Bright yellow crystals
Density 1.225g/cm3
Melting point 105 to 107 °C (221 to 225 °F; 378 to 380 K)
Boiling point 304.5 °C (580.1 °F; 577.6 K) @ 760mmHg
Insoluble
Pharmacology
ATC code B02BA02
Hazards
Flash point 113.8 °C (236.8 °F; 386.9 K)
Lethal dose or concentration (LD, LC):
0.5 g/kg (oral, mouse)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Menadione is a synthetic chemical compound sometimes used as a nutritional supplement because of its vitamin K activity. It is an analog of 1,4-naphthoquinone with a methyl group in the 2-position.[2]

Terminology

It is sometimes called vitamin K3,[3] although derivatives of naphthoquinone are not naturally occurring chemicals and therefore do not qualify as vitamins, and without the side chain in the 2-position they cannot exert all the functions of the K vitamins. Menadione is metabolized by the human body into K2 which uses alkylation to yield menaquinones (MK-n, n=1-13; K2 vitamers), hence is better classified as a provitamin.

It is also known as "menaphthone".[4]

Uses

Despite the fact that it can serve as a precursor to various types of vitamin K, menadione is generally not used as a nutritional supplement in economically developed countries. Menadione for human use at pharmaceutical strength is available in some countries with large lower income populations. It is used in the treatment of hypoprothrombinemia outside of the United States.

Toxicity

Large doses of menadione have been reported to cause adverse outcomes including hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency, neonatal brain or liver damage, or neonatal death in some rare cases. In the United States, menadione supplements are banned by the U.S. Food and Drug Administration because of their potential toxicity in human use.

Low-dose menadione is still used as an inexpensive micronutrient for livestock in many countries. Forms of menadione are also included in some pet foods in developed countries as a source of vitamin K. These doses have yielded no reported cases of toxicity from menadione in livestock or pets.

Experimental research

Recently, menadione in combination with vitamin C is being studied as a potential treatment for prostate cancer.[5][6]

A menadione topical lotion was recently developed to reduce epidermal growth factor receptor inhibitor-related side effects, by the prevention of skin toxicities that result from inhibition of protein kinases by drugs such as erlotinib (Tarceva) and cetuximab (Erbitux).[7][8]

References

  1. ↑ The Merck Index, 11th Edition, 5714
  2. ↑ Castro FA, Mariani D, Panek AD, Eleutherio EC, Pereira MD (2008). Fox, Debbie, ed. "Cytotoxicity Mechanism of Two Naphthoquinones (Menadione and Plumbagin) in Saccharomyces cerevisiae". PLoS ONE 3 (12): e3999. doi:10.1371/journal.pone.0003999. PMC 2600608. PMID 19098979.
  3. ↑ Scott GK, Atsriku C, Kaminker P, et al. (September 2005). "Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation and histone H3 arylation". Mol. Pharmacol. 68 (3): 606–15. doi:10.1124/mol.105.013474. PMID 15939799.
  4. ↑ "Vitamin K". Retrieved 2009-03-18.
  5. ↑ James M. Jamison, Jacques Gilloteaux, Henryk S. Taper and Jack L. Summers (2001). "Evaluation of the In Vitro and In Vivo Antitumor Activities of Vitamin C and K-3 Combinations against Human Prostate Cancer" (PDF). J. Nutr. 131 (1): 158S–160S. PMID 11208954.
  6. ↑ Tareen B, Summers JL, Jamison JM, Neal DR, McGuire K, Gerson L, Diokno A (2008). "A 12 Week, Open Label, Phase I/IIa Study Using Apatone® for the Treatment of Prostate Cancer Patients Who Have Failed Standard Therapy". Int J Med Sci 5 (2): 62–67. doi:10.7150/ijms.5.62. PMC 2288789. PMID 18392145.
  7. ↑ R. Perez-Soler, Y. Ling, Y. Zou, S.R. Deitcher (2008). "Local Rescue of Skin Toxicities Secondary to Kinase Inhibitor (KI) Therapy with Topical Menadione" (PDF). Annals of Oncology. doi:10.1093/annonc/mdn346.
  8. ↑ Tianhong Li and Roman Perez-Soler (2009). "Skin toxicities associated with epidermal growth factor receptor inhibitors". Targeted Oncology 4 (2): 107–119. doi:10.1007/s11523-009-0114-0. PMID 19452131.

External links

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