Furanocoumarin

Phytoalexins are low molecular weight compounds produced in plants as a defense mechanism against microorganisms. They do, however, exhibit toxicity to humans and other animals in addition to microbes (30). Coumarins, glycoalkaloids, isocoumarins, isoflavonoids, linear furanocoumarins, stilbenes, and terpenes aU. fall into the category of phytoalexins (31). Because phytoalexins are natural components of plants, and because their concentration may increase as a response to production and management stimuli, it is useful to recogni2e the possible effects of phytoalexins in the human diet. 

Fig. 4. Comparison of the two signal-reaction chains leading either to the UV light-induced formation of flavonoids or to the elicitor-induced formation of furanocoumarins and related compounds with antimicrobial activity. From Hahlbrock et al. (1985). PR -proteins are pathogenesis-related proteins.

CYP6D1 of the housefly (Musca domestica) has been found to hydroxylate cyper-methrin and thereby provide a resistance mechanism to this compound and other pyrethroids in this species (Scott et al. 1998 see also Chapter 12). Also, this insect P450 can metabolize plant toxins such as the linear furanocoumarins xanthotoxin and bergapten (Ma et al. 1994). This metabolic capability has been found in the lepi-dopteran Papilio polyxenes (black swallowtail), a species that feeds almost exclusively on plants containing furanocoumarins. 

Ma, R., Cohen, M.B., and Berenbaum, M.R. et al. (1994). Black swallowtail alleles encode cytochrome P450s that selectively metabolise linear furanocoumarins. Archives of Biochemistry and Biophysics 310, 332-340. 

The availability of North American specimens of Glehnia made it possible to compare coumarin and acetylene profiles of this widely disjunct system (Hiraoka et al., 2002). Analysis of plant material collected from four widely separated sites, that is, northern California, central Oregon, northern Washington, and northeastern Queen Charlotte Islands, British Columbia, revealed a profile characterized by low levels of furanocoumarins and a comparatively high level of panaxynol. The results are similar to those that characterize the southern Japanese form. The North American... 

Hiraoka, N., Chang, J.-L, Bohm, L. R. and Bohm, B. A. 2002. Furanocoumarin and polyacety-lenic compound composition of wild Glehnia littoralis in North America. Biochem. Syst. Ecol. 30 321-325. 

Itoh, A., Sasaki, K., Mizukami, H., Ohashi, H., Sakurai, T. and Hiraoka, N. 1997. Geographical variation in the furanocoumarin and polyacetylenic compound compositions of wild Glehnia littoralis plants. Nat. Med. 51 50-55. 

FIGURE 11.8 Correlation of R, values of selected furanocoumarins meassured on Florisil and silica layers developed with 5% diisopropyl ether in CH2CI2 + H (7 3) solid circles and with 15% AcOEt in B (open circles). For abbreviations see Figure 11.5. (For details, see Waksmundzka-Hajnos, M. and Wawrzynowicz, T., 7. Planar Chromatogr., 5, 169-174, 1992.)... 

P Schmeidlin-Ren, DJ Edwards, ME Fitzsimmons, K He, KS Lown, PM Woster, A Rahman, KE Thummel, JM Fisher, PF Hollenberg, PB Watkins. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab Dispos 25 1228-1233, 1997. 

Diawara M M, Trumble J T, Quiros C F and Hansen R (1995), Implications of distributions of linear furanocoumarins within celery , J Agric Food Chem, 43, 723-727. 

Nigg H N, Strandberg J O, Beier R C, Petersen H D and Harrison J M (1997), Furanocoumarins in Florida celery varieties increased by fungicide treatment , J Agric Food Chem, 45, 1430-1436. 

Figure 3.4. Synthesis of coumarin and furanocoumarin from p-coumaric acid.

Stanjek V, Piel J, Boland W (1999) Biosynthesis of furanocoumarins melvalonate-independent prenylation of umbelliferone in Apium graveolens (Apiaceae). Phytochemistry 50 1141-1146 Steinberg PD (1992) Geographical variation in the interaction between marine herbivores and brown algal secondary metabolites. In Paul V (ed) Ecological roles of marine natural products. Comstock, Ithaca, pp 51-92... 

The potent carcinogen aflatoxin B1 is activated by generation of an epoxide on a dihydrofuran moiety [43]. The potent MBIs contained in grapefruit juice and in the herbal medication St J ohn s Wort are furanocoumarin compounds [44—46]. A similar moiety is also incorporated in the HIV protease inhibitor L-754,394, a potent CYP3A4 MBI [47]. 

Other coumarin-related compounds include furans, found in moldy sweet potatoes, and the furan coumarin complexes (furanocoumarins) found in parsnip leaves (psoralens). They are photoreactive compounds (primary photosensitizers) that exacerbate sunburn to psoralen exposed skin. 

Larbat R, Kellner S, Specker S, Hehn A, Gontier E, Hans J, Bourgaud F, Matern U (2007) Molecular cloning and functional characterization of psoralen synthase, the first committed monooxygenase of furanocoumarin biosynthesis. J Biol Chem 282 542-554... 

Imperatorin (Fig. 4), a furanocoumarin produced hy Angelika dahurica var. formosana plants, is traditionally used in China for treating headaches and psoriasis. The combined treatment of A. dahurica cell cultures with 30-mg/L vanadyl sulphate and 20-g/L adsorvent amberlite XAD-7 resin provided -0.5 mg of imperatorin/g dw. ... 

There is some evidence for induction in pasture plants. A furanocoumarin, isopimpinellin, increases in floral stands of wild parsnip, Pastinaca sattva, after clipping that simulates herbivory (Nitao, 1988). 

Berenbaum, M. (1981). Patterns of furanocoumarin production and insect herbivory in a population of wild parsnip Pastinaca sativa L.). Oecologia 49,236-244. 

Nitao, J. K. (1988). Artificial defloration and furanocoumarin induction inPastinacasativa ( JmheWiferz.e). Journal of ChemicalEcology 14,1515. 

Zobel, A. M. and Brown, S. A. (1990). Dermatitis-inducing furanocoumarins on leaf surfaces of eight species of rutaceous and umbelliferous phms. Journal of ChemicalEcology 16,693-700. 

---