Bergapten – a phototoxic furanocoumarin – University of Copenhagen

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NaToxAq > Toxin of the week > Bergapten

13 November 2017

Bergapten – a phototoxic furanocoumarin

Natural toxin

Furanocoumarins are common in the Rutaceae (e.g. citrus fruits) and Umbelliferae (e.g. fennel, dill, parsley, celery, wild carrot, cow parsnip, giant hogweed) plant families. Many furanocoumarins are phototoxic and can cause phytophotodermatitis (skin inflammation and burns) upon exposure to light

Bergapten structure. Click image for 3D structure

The chemical structure of the parent furanochemicals consists of a furan ring fused with coumarin either linearly, producing psoralen, or angularly, producing angelicin. Bergapten (5-methoxypsoralen) is a psoralen derivative with an attached methoxy-group.

Both linear and angular furanocoumarins are toxic to herbivorous insects. However, particularly linear furanocoumarins show high phototoxicity resulting from crosslinking DNA pyrimidine bases in the presence of UV light. Already a very early study defined the criteria for coumarins to be phototoxic: 1) only coumarins with a furanocoumarin structure are phototoxic. Coumarin is not, 2) Linear furanocoumarins are much more active than angular ones, 3) The introduction of a OH group for example in psoralen removes activity, a methoxy-group does not remove activity, 4) Methyl groups reduce activity, 5) Introduction of nitro-, amino- and acetylamin groups cancel the activity.

In addition furanocoumarins react with oxygen generating singlet oxygen, hydroxy radicals and superoxide anion radicals. Furanocoumarins also bind to unsaturated fatty acids and proteins inhibiting enzymes.

Bergapten is found in large amounts in bergamot essential oil – used in perfumes – and giant hogweed. In total, furanocoumarins can constitute up to 4% dry weight of giant hogweed.

SMILES: COC1=C2C=CC(=O)OC2=CC3=C1C=CO3

References:

  • Hattendorf, J., Hansen, S. O. & Nentwig, W. in Ecology and Management of Giant Hogweed (Heracleum mantegazzianum  (eds P. Pysek, M.J.W. Cock, W. Nentwig, & H.P. Ravn) 209-225 (CAB International, 2007).
  • Moulton-Levy, N.M. & Maibach, H.I.. In Dermatotoxicology (eds. Wilhelm, K., Zhai, H., Maibach, H.I.) 209-213 (CRC Press, Taylor & Francis Group).
  • Musajo, L. & Rodighiero, G. SKIN-PHOTOSENSITIZING FUROCOUMARINS. Experientia 18, 153-&, doi:10.1007/bf02151700 (1962).
  • Rzymski, P., Klimaszyk, P. & Poniedzialek, B. Invasive giant hogweeds in Poland: Risk of burns among forestry workers and plant distribution. Burns 41, 1816-1822, doi:10.1016/j.burns.2015.06.007 (2015).
  • National Center for Biotechnology Information. PubChem Compound Database; CID=2355, https://pubchem.ncbi.nlm.nih.gov/compound/2355 (accessed Nov. 9, 2017).