The furanocoumarins, or furocoumarins, are a class of organic chemical compounds produced by a variety of plants. Most of the plant species found to contain furanocoumarins belong to a handful of plant families. The families Apiaceae and Rutaceae (citrus family) include the largest numbers of plant species that contain furanocoumarins [1] . The families Moraceae and Fabaceae include a few widely distributed plant species that contain furanocoumarins. [2]
Generally, furanocoumarins are most abundant in plants that have flowered and in ripe seeds and fruits. [2] (An exception is the common fig where furanocoumarins are found chiefly in the milky sap of the leaves and shoots but not the fruits. [3] ) During the early stages of plant growth, their presence is not easily detected.
The chemical structure of furanocoumarins consists of a furan ring fused with a coumarin. The furan ring may be fused in various ways, producing several different isomers. The parent compounds of the most common isomers are psoralen and angelicin. Derivatives of these two compounds are referred to respectively as linear and angular furanocoumarins, [4] so called since they exhibit a linear or angular chemical structure.
The compounds are biosynthesized partly through the phenylpropanoid pathway and the mevalonate pathway, which is biosynthesized by a coupling of dimethylallyl pyrophosphate (DMAPP) and 7-hydroxycoumarin (umbelliferone).
Many furanocoumarin compounds are toxic. The phytochemicals enter the nucleus of epithelial cells and form a bond (cross-linking) with the DNA when exposed to UV, which causes cell death and causes inflammation via activation of the arachidonic acid cascade. The result is known as phytophotodermatitis, a serious skin inflammation. [5]
Furanocoumarins produced by plants may serve as a defense mechanism against predators such as insects and mammals. [6] [7] It is also likely that furanocoumarins are related to a plant's natural defense against fungal attack. [8] In particular, the linear furanocoumarins (psoralen, bergapten, and methoxsalen), which occur naturally in Apiaceae, Rutaceae, and other plant families, are known to be toxic to fungi. [9] Plants that cause phytophotodermatitis usually contain linear furanocoumarins. [8]
Furanocoumarins are found in the sap of plants such as Ammi majus , parsnip, and giant hogweed. At least 36 species of the genus Heracleum in the family Apiaceae are known to contain one or more furanocoumarin compounds. [10]
The toxin can sometimes be found even in the most common foods, including carrots, parsley, limes, and lemons, as reported in the New England Journal of Medicine in the case of a man who manually squeezed a dozen limes and then inadvertently exposed his hand directly to the sunlight without precaution, triggering a severe phytophotodermatitis for several months. [11] The identified culprit was the prolonged exposure of his both hands to lime juice followed by that of sunlight UV. [11]
Furanocoumarins have other biological effects as well. For example, in humans, bergamottin and 6',7'-dihydroxybergamottin are responsible for the "grapefruit juice effect", in which these furanocoumarins affect certain P450 liver and gut enzymes, such as the inhibition of CYP3A4 which either activates or deactivates many drugs, thus leading to higher or lower levels in the bloodstream. [12] Furanocoumarins have various effects which can specifically increase or decrease (depending on the drug) the blood levels of many pharmaceuticals in ways that can be life-threatening, so FDA-approved drugs include warnings for grapefruit.
Apiaceae or Umbelliferae is a family of mostly aromatic flowering plants named after the type genus Apium, and commonly known as the celery, carrot or parsley family, or simply as umbellifers. It is the 16th-largest family of flowering plants, with more than 3,800 species in about 446 genera, including such well-known, and economically important plants as ajwain, angelica, anise, asafoetida, caraway, carrot, celery, chervil, coriander, cumin, dill, fennel, lovage, cow parsley, parsley, parsnip and sea holly, as well as silphium, a plant whose exact identity is unclear and may be extinct.
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of organic heterocycles.
Citrus is a genus of flowering trees and shrubs in the family Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, mandarins, lemons, grapefruits, pomelos, and limes.
Citrus hystrix, called the kaffir lime, Thai lime or makrut lime, is a citrus fruit native to tropical Southeast Asia.
A lime is a citrus fruit, which is typically round, green in color, 3–6 centimetres (1.2–2.4 in) in diameter, and contains acidic juice vesicles.
In chemistry, an open-chain compound or acyclic compound is a compound with a linear structure, rather than a cyclic one. An open-chain compound having no side groups is called a straight-chain compound. Many of the simple molecules of organic chemistry, such as the alkanes and alkenes, have both linear and ring isomers, that is, both acyclic and cyclic. For those with 4 or more carbons, the linear forms can have straight-chain or branched-chain isomers. The lowercase prefix n- denotes the straight-chain isomer; for example, n-butane is straight-chain butane, whereas i-butane is isobutane. Cycloalkanes are isomers of alkenes, not of alkanes, because the ring's closure involves a C-C bond. Having no rings, all open-chain compounds are aliphatic.
Heracleum is a genus of biennial and perennial herbs in the carrot family Apiaceae. They are found throughout the temperate northern hemisphere and in high mountains as far south as Ethiopia. Common names for the genus or its species include hogweed and cow parsnip.
Photodermatitis, sometimes referred to as sun poisoning or photoallergy, is a form of allergic contact dermatitis in which the allergen must be activated by light to sensitize the allergic response, and to cause a rash or other systemic effects on subsequent exposure. The second and subsequent exposures produce photoallergic skin conditions which are often eczematous. It is distinct from sunburn.
Methoxsalen sold under the brand name Oxsoralen among others, is a medication used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas in conjunction with exposing the skin to ultraviolet (UVA) light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. Levels of individual patient PUVA exposure were originally determined using the Fitzpatrick scale. The scale was developed after patients demonstrated symptoms of phototoxicity after oral ingestion of methoxsalen followed by PUVA therapy. Chemically, methoxsalen is a derivative of psoralen and belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan. It can also be injected and used topically.
Psoralen is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered as a derivative of umbelliferone. Psoralen occurs naturally in the seeds of Psoralea corylifolia, as well as in the common fig, celery, parsley, West Indian satinwood, and in all citrus fruits. It is widely used in PUVA treatment for psoriasis, eczema, vitiligo, and cutaneous T-cell lymphoma; these applications are typically through the use of medications such as Methoxsalen. Many furanocoumarins are extremely toxic to fish, and some are deposited in streams in Indonesia to catch fish.
Ammi majus, commonly called bishop's flower, false bishop's weed, laceflower, bullwort, etc., is a member of the carrot family Apiaceae. The plant, which has white lace-like flower clusters, has a large distribution through Southern Europe, North Africa and West and Central Asia, though it is hypothesized to be native to the Nile River Valley.
Bergamottin (5-geranoxypsoralen) is a natural furanocoumarin found in the pulp of pomelos and grapefruits. It is also found in the peel and pulp of the bergamot orange, from which it was first isolated and from which its name is derived.
Phytophotodermatitis, also known as berloque dermatitis, margarita photodermatitis, lime disease or lime phytodermatitis is a cutaneous phototoxic inflammatory reaction resulting from contact with a light-sensitizing botanical agent followed by exposure to ultraviolet A (UV-A) light. Symptoms include erythema, edema, blisters, and delayed hyperpigmentation. Heat and moisture tend to exacerbate the reaction.
Heracleum persicum, commonly known as Persian hogweed or by its native name golpar, is a species of hogweed, a perennial herbaceous plant in the carrot family Apiaceae. It grows wild in humid mountainous regions in Iran and some adjacent areas. Having been introduced in the 1830s, it has spread across Scandinavia. It is now very common in northern Norway, where one of its names is Tromsø palm. The plant has also been spotted in Sweden. In Finland, it has been declared an invasive species.
Bergapten (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot family Apiaceae and the citrus family Rutaceae. For example, bergapten has been extracted from 24 species of the genus Heracleum in the family Apiaceae. In the family Rutaceae, various Citrus species contain significant amounts of bergapten, especially the bergamot orange, the micrantha, and certain varieties of lime and bitter orange.
In coordination chemistry, denticity refers to the number of donor groups in a given ligand that bind to the central metal atom in a coordination complex. In many cases, only one atom in the ligand binds to the metal, so the denticity equals one, and the ligand is said to be unidentate or monodentate. Ligands with more than one bonded atom are called multidentate or polydentate. The denticity of a ligand is described with the Greek letter κ ('kappa'). For example, κ6-EDTA describes an EDTA ligand that coordinates through 6 non-contiguous atoms.
Angelicin is the parent compound in a family of naturally occurring organic compounds known as the angular furanocoumarins. Structurally, it can be considered as benzapyra-2-one fused with a furan moiety in the 7,8-position. Angelicin is commonly found in certain Apiaceae and Fabaceae plant species such as Bituminaria bituminosa. It has a skin permeability coefficient (LogKp) of -2.46. The maximum absorption is observed at 300 nm. The 1HNMR spectrum is available; the infrared and mass spectra of angelicin can be found in this database. The sublimation of angelicin occurs at 120 °C and the pressure of 0.13 Pa. Angelicin is a coumarin.
The micrantha is a wild citrus from the papeda group, native to southern Philippines, particularly islands of Cebu and Bohol. Two varieties are recognized: small-flowered papeda, locally known as biasong, and small-fruited papeda or samuyao.
Bergamot essential oil is a cold-pressed essential oil produced by cells inside the rind of a bergamot orange fruit. It is a common flavouring and top note in perfumes. The scent of bergamot essential oil is similar to a sweet light orange peel oil with a floral note.
6',7'-Dihydroxybergamottin is a natural furanocoumarin found in pomelos, grapefruits, and sour oranges, in both the peel and the pulp. Along with the chemically related compound bergamottin, it is believed to be responsible for a number of grapefruit–drug interactions, in which the consumption of citrus containing one or both of these compounds affects the metabolism of a variety of pharmaceutical drugs.