Coumarin derivatives are derivatives of

coumarin Coumarin () or 2''H''-chromen-2-one is an aromatic organic chemical compound with formula . Its molecule can be described as a benzene molecule with two adjacent hydrogen atoms replaced by an unsaturated lactone ring , forming a second six-me ...

and are considered

phenylpropanoids The phenylpropanoids are a diverse family of organic compounds that are biosynthesized by plants from the amino acids phenylalanine and tyrosine in the shikimic acid pathway. Their name is derived from the six-carbon, aromatic phenyl group and ...

. Among the most important derivatives are the 4-hydroxycoumarins, which exhibit

anticoagulant An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...

properties, a characteristic not present for coumarin itself. Some naturally occurring coumarin derivatives include

umbelliferone Umbelliferone, also known as 7-hydroxycoumarin, hydrangine, skimmetine, and ''beta''-umbelliferone, is a natural product of the coumarin family. It absorbs ultraviolet light strongly at several wavelengths. There are some indications that this c ...

(7-hydroxycoumarin),

aesculetin Aesculetin (also known as esculetin, 6,7-dihydroxycoumarin and cichorigenin) is a derivative of coumarin. It is a natural lactone that derives from the intramolecular cyclization of a cinnamic acid derivative. It is present in chicory and in many ...

(6,7-dihydroxycoumarin),

herniarin Herniarin is a natural chemical compound. Chemically, it can be considered a methoxy derivative of coumarin or a methyl derivative of umbelliferone. Herniarin is found in ''Herniaria glabra'', ''Ayapana triplinervis ''Ayapana triplinervis'' ( ...

(7-methoxycoumarin),

psoralen Psoralen (also called psoralene) 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 a ...

and

imperatorin Imperatorin is a furocoumarin and a phytochemical that has been isolated from ''Urena lobata'' L. (Malvaceae), ''Angelica archangelica'', ''Angelica dahurica'', '' Glehnia littoralis'', ''Saposhnikovia divaricata'', '' Cnidium monnieri'', '' Incarv ...

. 4-Phenylcoumarin is the backbone of the neoflavones, a type of neoflavonoids. Coumarin pyrazole hybrids have been synthesized from hydrazones, carbazones and thiocarbazones via Vilsmeier Haack formylation reaction. Compounds derived from coumarin are also called coumarins or coumarinoids; this family includes: *

brodifacoum Brodifacoum is a highly lethal 4-Hydroxycoumarins, 4-hydroxycoumarin vitamin K antagonist anticoagulant poison. In recent years, it has become one of the world's most widely used pesticides. It is typically used as a rodenticide, but is also used ...

bromadiolone Bromadiolone is a potent anticoagulant rodenticide. It is a second-generation 4-hydroxycoumarin derivative and vitamin K antagonist, often called a "super- warfarin" for its added potency and tendency to accumulate in the liver of the poisone ...

difenacoum Difenacoum is an anticoagulant of the 4-hydroxycoumarin vitamin K antagonist type. It has anticoagulant effects and is used commercially as a rodenticide Rodenticides are chemicals made and sold for the purpose of killing rodents. While commo ...

auraptene Auraptene is a natural bioactive monoterpene coumarin ether. It was first isolated from members of the genus ''Citrus ''Citrus'' is a genus of flowering trees and shrubs in the family Rutaceae. Plants in the genus produce citrus fruits, in ...

ensaculin Ensaculin (KA-672) is a drug from the coumarin family, which has been researched as a potential treatment for dementia. It acts on a number of receptor systems, being both a weak NMDA antagonist and a 5HT1A agonist. Animal studies have shown pro ...

phenprocoumon Phenprocoumon (marketed under the brand names Marcoumar, Marcumar and Falithrom) is a long-acting anticoagulant to be taken by mouth, and a coumarin derivative. It acts as a vitamin K antagonist and inhibits blood clotting (coagulation) by blocki ...

(Marcoumar) *

PSB-SB-487 PSB-SB-487 is an experimental drug which is used as a pharmacological research tool. It is a coumarin derivative which is an antagonist at the former orphan receptor GPR55. Unlike older GPR55 antagonists such as O-1918, PSB-SB-487 has good se ...

PSB-SB-1202 PSB-SB-1202 is a coumarin derivative which is an agonist at the cannabinoid receptors CB1 and CB2, with a CB1 Ki of 32nM and a CB2 Ki of 49nM. It is also a weak antagonist at the related receptor GPR55, with an IC50 of 6350nM, but has no signif ...

scopoletin Scopoletin is a coumarin found in the root of plants in the genus '' Scopolia'' such as ''Scopolia carniolica'' and '' Scopolia japonica'', in chicory, in '' Artemisia scoparia'', in the roots and leaves of stinging nettle (''Urtica dioica''), in t ...

can be isolated from the bark of ''Shorea pinanga'' *

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

(Coumadin) Coumarin is transformed into the natural

dicoumarol Dicoumarol ( INN) or dicumarol ( USAN) is a naturally occurring anticoagulant drug that depletes stores of vitamin K (similar to warfarin, a drug that dicoumarol inspired). It is also used in biochemical experiments as an inhibitor of reductase ...

by a number of species of

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

. This occurs as the result of the production of

4-hydroxycoumarin 4-Hydroxycoumarin is a coumarin derivative with a hydroxy group at the 4-position. Occurrence 4-Hydroxycoumarin is an important fungal metabolite from the precursor coumarin, and its production leads to further fermentative production of the n ...

, then further (in the presence of naturally occurring

formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...

) into the actual anticoagulant

, a fermentation product and

mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξικός , "poisonous") is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually rese ...

. Dicoumarol was responsible for the bleeding disease known historically as "

sweet clover ''Melilotus'', known as melilot or sweet clover is a genus of legumes in the family Fabaceae, native to Europe, Asia, and Africa. The genus is closely related to ''Trifolium'' (clovers). Several species are common grassland plants and weeds of ...

disease" in cattle eating moldy sweet clover

silage Silage is fodder made from green foliage crops which have been preserved by fermentation (food), fermentation to the point of souring. It is fed to cattle, sheep and other ruminants. The fermentation and storage process is called ''ensilage'', ' ...

. In

basic research Basic research, also called pure research, fundamental research, basic science, or pure science, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenome ...

, preliminary evidence exists for coumarin having various biological activities, including

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

anti-tumor Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a cu ...

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

, and

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

properties, among others.

Uses

Medicine

Warfarin – a coumarin – with

brand name A brand is a name, term, design, symbol or any other feature that distinguishes one seller's goods or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create and ...

, ''Coumadin'', is a prescription drug used as an anticoagulant to inhibit formation of blood clots, and so is a

therapy A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx. As a rule, each therapy has indications a ...

for

deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enl ...

and

pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain ...

. It may be used to prevent recurrent blood clot formation from

atrial fibrillation Atrial fibrillation (AF, AFib or A-fib) is an Heart arrhythmia, abnormal heart rhythm (arrhythmia) characterized by fibrillation, rapid and irregular beating of the Atrium (heart), atrial chambers of the heart. It often begins as short periods ...

, thrombotic stroke, and transient ischemic attacks. Coumarins have shown some evidence of biological activity and have limited approval for few medical uses as pharmaceuticals, such as in the treatment of

lymphedema Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized edema, swelling caused by a compromised lymphatic system. The lymphatic system functions as a critical portion of the body's immune system and returns inters ...

. Both coumarin and 1,3-indandione derivatives produce a

uricosuric Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule of the kidney. ...

effect, presumably by interfering with the

renal tubular The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...

reabsorption of

urate Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown of ...

Laser dyes

Coumarin dyes are extensively used as gain media in blue-green tunable organic

dye lasers A dye laser is a laser that uses an organic dye as the lasing medium, usually as a liquid solution. Compared to gases and most solid state lasing media, a dye can usually be used for a much wider range of wavelengths, often spanning 50 to 100 n ...

. Among the various coumarin

laser dye file:Coherent 899 dye laser.jpg, Close-up of a table-top dye laser using Rhodamine 6G as active medium. file:rhodamine 6G.svg, Molecular structure of Rhodamine 6G, perhaps the best known laser dye. A Laser dye is a dye used as laser medium in a dy ...

s are coumarins 480, 490, 504, 521, 504T, and 521T. Coumarin tetramethyl laser dyes offer wide tunability and high laser gain, and they are also used as active medium in coherent

OLED An organic light-emitting diode (OLED), also known as organic electroluminescent (organic EL) diode, is a type of light-emitting diode (LED) in which the emissive electroluminescent layer is an organic compound film that emits light in respon ...

emitters. and as a sensitizer in older

photovoltaic Photovoltaics (PV) is the conversion of light into electricity using semiconducting materials that exhibit the photovoltaic effect, a phenomenon studied in physics, photochemistry, and electrochemistry. The photovoltaic effect is commercially ...

technologies.

References

{{reflist Coumarins Phenylpropanoids