Sursa: therapeutic-role-of-coumarins-and-coumarinrelated-

compounds-2157-7544-5-130

Therapeutic Role of Coumarins and Coumarin-Related

Compounds
Rohini K1* and Srikumar PS2
1 Unit of Biochemistry, Faculty of Medicine, AIMST University, Bedong, 08100, Malaysia
2 Unit of Psychiatry, Faculty of Medicine, AIMST University, Bedong, 08100, Malaysia

Rolul therapeutic al cumarinelor si a compusilor inruditi

cu acestea (autor Rohini K1* si Srikumar PS2)
Coumarins are a group of polyphenolic compounds isolated
from plant product Tonka bean, coumarou in 1820. Coumarins are
colorless and crystalline phytochemical substances [1]. It is an oxygen
heterocycle, which occurs either in free or combined form with
glucose. They belong to the family of benzopyrones, which consists
of benzene ring joined by a pyrone ring Figure 1 [2,3]. Benzopyrones
are subdivided into benzo--pyrones and benzo--pyrones of which
coumarins and flavonoids are prime members of benzo--pyrones and
benzo- pyrones class respectively. The biochemical, pharmacological
and therapeutic applications of simple coumarins could be influenced
by the substitution pattern. Studies have proven that coumarins act as
competitive inhibitors of vitamin K. Other intricate compounds are
based on the coumarin nucleus which comprises of the anticoagulants
like warfarin, aflatoxins and the psoralens [4]. Studies have also
shown that they function as blood diluting agent and also exhibits
anti-fungicidal property. Researches have also proved the selective
cytotoxicity of coumarins for tumor cells and also the effect of
coumarins in the regulation of immune response, cell growth and
differentiation [5]. Nowadays, coumarins are also used as additives in
food and cosmetic industry, as laser dyes, agrochemical industries and
also as optical brightening agents. Studies have proven that it possesses
anti-aging, and cardioprotective function.

Traducere: Cumarine sunt un grup de compui polifenolici izolai

de produs vegetal Tonka fasole, coumarou n Cumarinele sunt 1820
Substane fitochimice incolore i cristaline [1]. Este un atom de oxigen
heterociclu, care are loc fie n form liber, fie combinat cu
glucoz. Acestea fac parte din familia lui benzopyrones, care const
de inel benzen unite printr-un inel de piron Figura 1 [2,3]. Benzopyrones
sunt subdivizate n benzo-a-pirone i benzo-y-pirone din care
cumarine i flavonoide sunt membri principali ai benzo-a-pirone i
benzo- -pyrones clasa respectiv. Efectele biochimice, farmacologice
si aplicatii terapeutice ale cumarine simple pot fi influenate
prin modelul de substituie. Studiile au demonstrat c acioneaz ca cumarine
inhibitori competitivi ai vitaminei K. Ali compui sunt complicate
bazat pe nucleul cumarina, care cuprinde anticoagulante
cum ar fi warfarina, aflatoxine i psoralens [4]. Studiile au, de asemenea,
artat c acestea funcioneaz ca agent de diluare de snge i, de asemenea, prezint
proprietate anti-fungic. Cercetrile au demonstrat, de asemenea, selective
citotoxicitatea cumarine pentru celulele tumorale i, de asemenea, efectul

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cumarine n reglarea rspunsului imun, creterea celular i
difereniere [5]. In prezent, cumarine sunt de asemenea utilizate ca aditivi n
industria alimentar i cosmetic, ca i colorani cu laser, industriile agro-chimice i
De asemenea, ca ageni optici de albire. Studiile au demonstrat c posed
anti-mbtrnire, i funcia cardioprotectoare.

The four main classifications of coumarins are simple coumarins,

furanocoumarins, pyrano coumarins and pyrone substituted
coumarins [6]. The features of four main coumarin subtypes are
listed in the Table 1 and Figure 1. Coumarin covers a very wide range
of compounds throughout the plant kingdom and are found rich in
fruits, roots, stems and leaves. They are rich in cassia leaf oil, lavender
oil and cinnamon bark oil. Richest sources are found in Rutaceae and
Umbelliferone. Coumarins are also found in selective microorganisms.
Members of coumarins isolated from microbial sources are novobiocin
from Streptomycin and aflatoxin from Aspergillus species. They are also
used as enhancing agent in cosmetic products like perfumes, soap,
detergents, toothpaste and alcoholic beverages [7]. It is also used as a
neutralizer in rubber and plastic materials and also in paints and sprays
to dilute the unpleasant odors [8].

Traducere: Cele patru clasificri principale ale cumarine sunt simple, cumarine,
furanocumarinele, cumarine pirano i piron substituit
cumarine [6]. Caracteristicile patru subtipuri principale cumarinice sunt
prezentate n Figura 1 i Tabelul 1. cumarin acoper o gam foarte larg
de compui pe tot regnul vegetal i se gsesc bogate n
fructe, rdcini, tulpini i frunze. Ele sunt bogate in ulei de frunze de cassia, lavanda
i ulei de scorioar scoar de copac. Sursele se gsesc cele mai bogate n Rutaceae i
Umbeliferona. Cumarine sunt, de asemenea, gsite n microorganisme selective.
Membrii de cumarine izolate din surse microbiene sunt novobiocina
din streptomicin i aflatoxin din specii de Aspergillus. Ele sunt, de asemenea,
utilizat ca agent de cretere n produsele cosmetice, cum ar fi parfumuri, spun,
detergeni, past de dini i buturi alcoolice [7]. De asemenea, este utilizat ca
neutralizer din materiale din cauciuc i plastic i, de asemenea, n vopsele i spray-uri
pentru a dilua mirosurile neplcute [8].

Coumarins possess a wide range of pharmaceutical actions and

biological functions and has great importance in the use of medicine
and also used for treating various clinical conditions. They exhibit
significant pharmacokinetic activity due to its rapid absorption and
metabolism [9] in the body. Coumarins have a significant effect on
physiological, bacteriostatic and anti-tumor activity. Table 2 shows the
list of coumarins and its therapeutic functions.
Traducere: Cumarine posed o gam larg de proprietati farmaceutice i
funcii biologice i au o mare importan n utilitatea medicinei farmaceutice.
De asemenea, sunt folosite pentru tratarea diferitelor afeciuni clinice. Ele prezint
Activitatea farmacocinetic semnificativ datorit absorbiei sale rapide i
Metabolismul [9] n organism. Cumarine au un efect semnificativ asupra
activitatii fiziologice, bacteriostatice i antitumoral. Tabelul 2 prezint
List de cumarine i a funciilor sale terapeutice.

Coumarin derivatives are also prime oral anticoagulants. They

exhibit therapeutic effect by acting as competitive inhibitors in the
coagulation cascade pathway. They inhibit the function of vitamin K

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which is required for the biosynthesis of prothrombin. Thus, coumarins
exhibit a desired therapeutic effect of anticoagulation by controlling
blood fluidity and removal of toxic effect of bleeding [10].

Traducere: Derivaii de cumarine sunt, de asemenea, anticoagulante orale prime. ele

prezint un efect terapeutic prin care acioneaz ca inhibitori competitivi pe
de coagulare n cascad cale. Ele inhib funcia de vitamina K
care este necesar pentru biosinteza protrombinei. Astfel, cumarine
prezint un efect terapeutic dorit de anticoagulare prin controlul
fluiditatea sngelui i eliminarea efectului toxic al hemoragiilor [10].

The mechanism of action of anti-tumor drugs is basically to target

the dividing cells that disturb cell division. Although new techniques
like chemotherapy and radiotherapy provide best results for the
treatment for cancer it triggers various side effects. Coumarins are
effective not only for treatment of cancer, but also to treat the side
effects caused by radiotherapy. Coumarins are very significant in the
treatment of cancer and is used in the treatment of prostate cancer,
renal cell carcinoma and leukemia [11,12]. Coumarins have found to
have good maintenance therapy in case of melanoma and also found
to inhibit the spread of tumors. Coumarins are very significant in
the treatment of cancer due to its non- toxic, anticoagulant property.
Coumarins have a cytotoxic mechanism and used as cell lines and has a
potential therapeutic function in renal cell carcinoma [13]. Coumarin
due to its hormonal sensitivity and immune modulating effects is
significant in the treatment of prostate cancer. Coumarin derivatives
like furanocomarins, pyranocoumarins, isoflavones, benzopyrones
have a significant role in the treatment of different cancer conditions.

Traducere: Mecanismul de aciune al medicamentelor anti-tumorale este, menit n

principiu s vizeze
celulele de divizare care perturb diviziunea celular. Cu toate c noile tehnici
cum ar fi chimioterapia si radioterapia ofera cele mai bune rezultate pentru
tratament impotriva cancerului declanseaza diverse efecte secundare. Cumarinele sunt
eficiente nu numai pentru tratarea cancerului, dar, de asemenea, pentru a trata latura
Efectele cauzate de radioterapie. Cumarine sunt foarte semnificative n ceea ce
tratamentul cancerului i este utilizat n tratamentul cancerului de prostat,
carcinom cu celule renale i leucemia [11,12]. Cumarine s-au dovedit a
au o bun terapie de ntreinere n caz de melanom i, de asemenea, gsite
pentru a inhiba rspndirea tumorilor. Cumarinele sunt foarte semnificative n
tratamentul cancerului, datorit proprietii sale non-toxice, anticoagulant.
Cumarinele au un mecanism citotoxic i utilizate ca linii celulare i are o
poteniala funcie terapeutic n carcinomul cu celule renale [13]. Cumarinele
datorit sensibilitii sale hormonale i efectele modulatoare ale sistemului imunitar este
semnificative n tratamentul cancerului de prostat. derivai de cumarin
cum ar fi furanocomarins, pyranocoumarins, izoflavone, benzopyrones
au un rol semnificativ n tratamentul strilor de cancer diferite.

Chronic infections
Coumarins are used as immunostimulatory drug for the treatment

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of chronic infections. The mechanism of action involves the activation
of macrophages inducing the cells of the immune response. Coumarins
are used in the treatment of chronic infections like mononucleosis,
toxoplasmosis, Q-fever, mycoplasmosis and chronic brucellosis [14].
Antiplasmodium drug isolated from the roots of Toddalia asiatica is
used in the treatment of malaria.
Inflammation
Inflammatory mechanism is due to an injury or effect of infectious
agents. Coumarins are potent anti-inflammatory drugs and it directs
against cell-adhesion molecules, thus highly significant in inflammatory
responses [10].
Edema
Coumarins have potent edema protective function and thus
involved in the treatment of lymphedema, elephantiasis and other high
protein edema conditions [15]. Edema results in the accumulation
of protein, resulting in delayed wound healing. Benzopyrones are
effective for the treatment of high protein edema. Several studies have
shown that coumarin reduces edema in rodents caused due to thermal
damage by effectively reducing the level of protein in the tissues [15,16].
Administration of coumarins along with vasoactive drugs has a very
high beneficial effect in the treatment of edema. Studies have reported
that the action of coumarin is by the binding to the plasma proteins and
thereafter activate the macrophage and proteolysis [17].

infeciile cronice
Cumarinele sunt utilizate ca medicament pentru tratamentul imunostimulator
infeciilor cronice. Mecanismul de aciune implic activarea
macrofagelor inductoare celulele rspunsului imun. Cumarinele
sunt utilizate n tratamentul infeciilor cronice cum ar fi mononucleoza,
toxoplasmoza, febra Q, micoplasmoze i bruceloza cronic [14].
Antiplasmodium de droguri izolat din rdcini de Toddalia Asiatica este
utilizat n tratamentul malariei.
Inflamaiile
Mecanismul inflamator se datoreaza unei leziuni sau a efectului de infecioase
ageni. Cumarine sunt medicamente anti-inflamatorii puternice i direcioneaz
mpotriva moleculelor de adeziune celular, fiind astfel extrem de semnificative n
inflamatorii
Rspunsurile [10].
Edem
Cumarine au funcia de protecie edem puternic i, prin urmare,
implicat n tratamentul limfedemul, elefantiazis i alte high?
Condiii Edem proteine [15]. Rezultatele Edem n acumularea
de proteine, ceea ce duce la vindecarea rnilor ntrziat. Benzopyrones sunt
eficace pentru tratamentul edemelor ridicat de proteine. Mai multe studii au
artat c cumarina reduce edemul la roztoare cauzate din cauza termice
daune prin reducerea n mod eficient nivelul de proteine n esuturi [15,16].
Administrarea de cumarine, mpreun cu medicamente vasoactive are o foarte
efect benefic ridicat n tratamentul edemelor. Studiile au raportat
c aciunea cumarinei este prin legarea la proteinele din plasm i
apoi activarea macrofagelor i proteoliza [17].

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Conclusion
The coumarins are of great attention due to their therapeutic
property. Their physiological, bacteriostatic and anti-tumor activity
marks coumarins as novel ones for therapeutic applications. Several
researchers have reported the clinical applications of coumarins and
coumarin derivatives in the treatment of several diseases. Several
studies have proven multiple potential role of coumarins which
includes disease spread and prevention, growth modulation, antioxidant
and anti-tumor effects.

Concluzii
Cumarinele sunt de o mare importanta datorit proprietatilor terapeutice ale acestora.
fiziologice Activitatea lor, bacteriostatice i anti-tumorale
Calificativele cumarine ca cele noi pentru aplicaii terapeutice. cteva
cercetatorii au raportat aplicaiile clinice ale cumarinicelor i
derivai de cumarin n tratamentul mai multor boli. cteva
Studiile au demonstrat multiple rolul potenial al cumarine, care
include rspndirea i prevenirea bolilor, modularea creterii, antioxidant
i efecte anti-tumorale.