Antioxidant Activity of Coumarins

Al-Majedy, Al-Amiery, Kadhum, and BakarMohamad: Antioxidant Activity of Coumarins

Authors

INTRODUCTION

Antioxidants in food play an important role as a health-protecting factor. Scientific evidence suggests that antioxidants reduce the risk for chronic diseases including cancer and heart disease. Primary sources of naturally occurring antioxidants are whole grains, fruits and vegetables. Plant sourced food antioxidants like vitamin C, vitamin E, carotenes, phenolic acids, phytate and phytoestrogens have been recognized as having the potential to reduce disease risk. Most of the antioxidant compounds in a typical diet are derived from plant sources and belongs to various classes of compounds with a wide variety of physical and chemical properties. Some compounds, such as gallates have strong antioxidant activity, while others, such as the mono-phenols are weak antioxidants. Coumarin and its derivatives represent one of the most active classes of compound possessing a wide spectrum of biological activity.14 Many of these compounds have proven to be active as antibacterial,57 antifungal,8 anti-inflammatory,9 anticoagulant,10 anti-HIV11 and antitumor agents.12 Coumarins are widely used as additives in food, perfumes, cosmetics,13 pharmaceuticals and optical brighteners14 and would dispersed fluorescent and laser dyes.15 Coumarins also have the super thermal stability and outstanding optical properties including extended spectral response, high quantum yields and superior photo stability. Optical applications of these compounds, such as laser dyes, nonlinear optical chromophores, fluorescent whiteners, fluorescent probes, polymer science, optical recording and solar energy collectors have been widely investigated.1620 Classical routes to coumarins incorporate Pechmann, Knoevenagel, Perkin, Reformat sky, and Wittig condensation reactions.2124 To make these classical reactions efficacious, several variations in terms of catalyst and reaction conditions have been introduced.25,26 Now when coumarin ring fused with other rings showing a synergistic effect of both the rings in their biological activities are obtained. Such compounds are exploited in development of various important molecule which provides scaffolds for drug development. Various moieties when combined with coumarin can produces same or different effects but with different potencies.27 In continuation of previous studies2837 on coumarins, herein we are reporting a review for such recent derivatives of coumarins with antioxidant activities.

Antioxidant Activity

Singh OM et al. developed a facile, convenient and high yielding synthesis of a combinatorial library of 3-alkanoyl/aroyl/heteroaroyl-2H-chromene-2-thiones (1). The assessment of radical scavenging capacity of the compounds towards the stable free radical 2,2-diphenyl-1- picrylhydrazyl (DPPH) was measured and these compounds were found to scavenge DPPH free radicals efficiently. The newly synthesized compounds exhibited profound antioxidant activity. Five selected compounds were able to protect curcumin from the attack of sulphur free radical generated by radiolysis of glutathione (GSH).38

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg024.jpg

R1= substituted phenyls, hetrocyclic nuclei / R2= -H, -Br / R3= -H, -OCH3 Abdullah S et al. synthesized a series of coumarin derivatives (2,3) and these compounds were evaluated for their in-vitro antioxidant activity and in-vivo anti antibacterial activity. These derivatives were found to possess the mentioned activities and on the basis of results, structure activity relationships (SAR) were developed in order to define the structural features required for activity.39

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg024a.jpg

Ravi. S et al. synthesized three derivatives of 4-methyl chromen- 2-one-compounds (4,5,6). Their antioxidant activity were expressed as IC50 with different antioxidant. The calculated values for three 4- methyl chromen- 2-one derivatives and using callic acid as reference were (2.04 μg/ ml,1.98 μg/ml, 15.0698 μg/ml, 0.0298 μg/ml for DPPH method), (3.72 μg/ml, 43.57 μg/ml,40.13 μg/ml,0.28μg/ml for nitric oxide method).40 The antioxidant study was also carried out by using phosphor molybdenum assay method, showed that the test samples had good antioxidant activity. Free radical scavenging activity of the coumarin compounds is concentration dependent. The concentration of the test compounds increases, the radical scavenging activity also increases and lower IC50 value reflects better protective action. The anti-oxidant activity of these 4-methyl chromen-2-one derivatives could be attributed to electron donating nature of the substituents like -OH, -CH3, -C6H5 on coumarin scaffold, which reduce free radicals and prevent the damage of cell. The more the hydrogen donors, the stronger is the anti-oxidant activity.41,42

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg025.jpg

Maja. M et al. synthesized a series of coumarin derivatives compounds (7,8,9,10). These compounds were evaluated for their in-vitro antioxidant activity.43 These compounds contain 3,4-dihydroxyphenyl and 2,5-dihidroxyphenyl ring with these substituents. The compounds was expected to possess antioxidant activity since hydrogen donation leads to formation of a stable quinoid structure. It has been reported that two hydroxyl groups in ortho position are important for antioxidant activity.44-46

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg025a.jpg

Melagraki .G et al. synthesizeda series of novel coumarin-3-carbox-amides (11) and the synthesis compounds were evaluated for their in-vitro antioxidant activity and in-vivo anti-inflammatory activity. These derivatives were found to possess the mentioned activities and on the basis of results, structure activity relationships (SAR) were developed in order to define the structural features required for activity.47

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg025b.jpg

Roussaki M et al. Synthesized a series of coumarin analogues (12) bearing a substituted phenyl ring on position 3. In vitro antioxidant activity of the synthesized compounds was evaluated using two different anti-oxidant assays. Ability of the compounds to inhibit soybean lipoxygenase was also determined as an indication of potential anti-inflammatory activity.48

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg025c.jpg

Stanchev S et al. synthesized four 4-hydroxycoumarin derivatives (13,14,15,16). These compounds were tested for in vitro antioxidant activity in hypochlorous system. The assay was based on the luminal-dependent chemiluminescence of free radicals, which decreased in the presence of 4-hydroxycoumarin derivative compound (16) expressed the best scavenger activity at the highest concentration (10–4 molL-1).49

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg025d.jpg

Per-oxidation activity, substituent on the aromatic ring of the benzopyranone moiety, the presence of electron-withdrawing groups on the phenyl ring of position 3 favours activity. The best combined pharmacological profile is exhibited by compound 17.50

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg025e.jpg

Substituted hydroxycoumarins and 7- or 8-hydroxybenzo (f) coumarins were prepared by the treatment of phenols and naphtha lenediols, respectively, with malic acid and H2SO4 under microwave irradiation. It has been identified that phenolic compounds present antioxidant activity. The presence of the phenolic hydroxyl group (6-, 7- or 8- ) seems to support the antioxidant activity but the effect on activity is independent of the position of hydroxyl group. It is generalized that the benzo derivative compound 2 is more potent than any of the cyclohexyl derivatives. Compound (18) shows higher antioxidant activity among various hydroxybenzo coumarins being synthesized.51

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg026.jpg

Different substituted 3, 3’-arylidenebis-4-hydroxycoumarins and tetrakis-4-hydroxycoumarin derivative (compound 3) were synthesized by 4-hydroxycoumarin and aromatic aldehydes containing different groups in ortho, Meta or para positions and condensing them in boiling ethanol or acetic acid. A possible relationship between intermolecular hydrogen-bonded structures and the antioxidant activities of these compounds are analyzed. The compounds which contain intermolecular hydrogen bonds is uncoupler and inhibitor of mitochondrial oxidative phosphorylation, while compounds which can only form intermolecular hydrogen bonds, is only uncoupler of oxidative phosphorylation. Thus, the formation of hydrogen bonds may be an important factor in assisting the synthesized dicoumarols (specifically compound 19) to attain the correct configuration for antioxidant activities.52

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg026a.jpg

Rajesh net al. Synthesized a series of coumarin derivatives and these compounds were evaluated for their in-vitro antioxidant activity and in-vivo anti anticancer activity, The newly synthesized compounds exhibited profound antioxidant activity and The presence of the phenolic hydroxyl group seems to support the antioxidant activity.53

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg026b.jpg

Shivani Ch et al. Synthesized new coumarin substituted derivatives of benzothiazole and they were evaluated for antioxidant activity by DPPH radical scavenging activity. The test compound (24) showed good in-vitro antioxidant activity.54

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg026c.jpg

Milan Ca et al. Synthesized a series of newly di-substituted and trisubstituted 1,3,4-thiadiazines with various substituents was prepared utilizing different thiosemicarbazides and 3-a-bromoacetylcoumarins as starting compounds. All of the new thiadiazine derivatives were tested for their antioxidant activity, employing different antioxidant assays (DPPH scavenging activity, iron chelating activity, power reducing activity). Compounds 25,26,27 and 28 were proven to be the best DPPH radical scavengers.55

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg026d.jpg

Y. Sri Ranganath et al .synthesized coumarine derivatives by reacting different para substituted acyl bromides with 4-methyl-7-hydroxy coumarin followed by cyclization in acidic medium. These compounds were screened for free radical scavenging activity by DPPH method and preliminary cytotoxic activity by using Ehrlich Ascites Carcinoma cells and Tryptan blue dye exclusion method. Among the compounds tested for radical scavenging and cytotoxic studies, 29 and 30 showed appreciable results when compared with the standard drugs ascorbic acid and 5- fluorouracil respectively.56

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg026e.jpg

Patel R. et al. Synthesized a series of coumarin derivatives compounds (31,32,33)these compounds were evaluated for their in-vitro antioxidant activity by DPPH free radical scavenging method, Super oxide method and Nitric oxide method. The value was determined for each compound From results of DPPH, Super oxide and Nitric oxide methods, it found that compound 31 and 32 displayed strong antioxidant activity compared to the ascorbic acid and compound 33 is also showed good anti-oxidant activity.57

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg027.jpg

Mahmoud M et al. Synthesizeda novel series of compounds containing coumarinyl moiety derivatives from 2-(2-oxo-4-phenyl- 2H-chromen-7-yloxy)-acetohydrazide and evalution the antioxidant activity. The effect of the different synthetic compounds on DPPH radical scavenging was compared to ascorbic acid using as positive control and appreciated by the determination of the IC 50 values, it found that compound 34 displayed strong antioxidant activity.58

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg027a.jpg

Abdul A. et al. Synthesized 3-Aminocoumarin as aligand ( L)for the formation of Cr(III), Ni(II), and Cu(II) complexes. Then determined the free radical scavenging activity of metal complexes by measuring their interaction with the stable free radical DPPH and all the compounds have shown encouraging antioxidant activities. Compound (35) is also found to be a superior antioxidant complex as compared to ascorbic acid.59

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg027b.jpg

Rajasekaran S. et al. A series of some coumarinyl and chromensulfanyl derivatives have been synthesized by conventional methods and in vitro antioxidant activity by 1,1- Diphenyl-2,2-picryl hydrazyl free radical (DPPH) method and compounds 36,37 were proven to be the best DPPH radical scavengers.60

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg027c.jpg

Abdul A.et al. synthesized two coumarins namely, N-(4,7-dioxo-2-phenyl-1,3-oxazepin-3(2H,4H,7H)-yl)-2-(2-oxo-2H-chromen-4-yloxy) acetamide(38) and N-(4-oxo-2-phenylthiazolidin-3-yl)-2-(2-oxo-2H-chromen-4-yloxy)acetamide (39) then study the compounds with the DPPH, hydrogen peroxide and nitric oxide radical methods and compared with the known antioxidant ascorbic acid. Compounds (38) and (39) were displayed strong antioxidant activity.61

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg027d.jpg

Nishiyama .T et al. Compared the antioxidative activities of seven hydrocoumarins with those of alphatocopherol for the oxidation of tetralin and linoleic acid in a homogeneous solution. Hydro coumarins exhibited a higher induction period than that of alpha-Toc in both systems. However, the rate of oxygen absorption during the induction period for alpha-Toc was slower than that of the hydro coumarins in both systems. In addition, 6,7-dihydroxy-4,4-dimethylhydrocoumarin (40) showed less cytotoxicity toward human fibroblasts than did 2, 6-di-t-butyl-4-methylphenol.62

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg027e.jpg

Saleta V et al. we have confirmed the considerable antioxidant activity of new hydroxylated coumarin-chalcone hybrid compounds 41-44 Their antioxidant activity is affected by the introduction of a benzoyl moiety at the C3 position regarding to the coumarin ring. A very interesting finding is that compound 41 is very reactive and presents good antioxidant capacity against hydroxyl and peroxyl radicals as well as low oxidation potential. In spite of the moderate trypanocidal activity of coumarin-chalcone hybrids, they have been proved to be very good antioxidants. Based on these results, we can conclude that compounds 42 and 43 are potential candidates for in vitro studies of their antioxidant activity.63

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg027f.jpg

Jayashree B.S. et al. Synthesized novel coumarin analogues, the synthesized compounds have shown free radical scavenging activity by DPPH and Nitric oxide scavenging activity and none of the compounds shown effective antidiabetic activity.64

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg028.jpg

Witaicenis et al. showed that treatment with esculetin (compound 49) and 4-methylesculetin prevent the colonic damage induced by tri nitro benzene sulphonic acid (TNBS) in rats and also that the presence of methyl group at C-4 in the esculetin molecule improves its antioxidant and intestinal anti-inflammatory activities.65

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg028a.jpg

Chang et al. demonstrated that 7- hydroxyl coumarin (umbelliferone) plays a very important role in XO inhibition. Furthermore, some 5,7-dihydroxycoumarins could significantly suppress signals generated by the X/XO system at a low concentration (20 mM) and, among them, the compound 5,7-dihydroxy-6-(3-methyl-butyryl)-4-ethyl- chromen-2-one (compound 50) was the best radical scavenger.66

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg028b.jpg

Yang et al. Reported that most hydroxylated 3- phenyl coumarins (stilbene-coumarin hybrids) are effective antioxidants against AAPH-induced pBR322 DNA strand breakage (compound 51).67

https://s3-us-west-2.amazonaws.com/jourdata/srp/SysRevPharm-8-24-pg028c.jpg

Natella et al. The presence of the ethoxy carbonylethyl group in DHMC at C-3 position significantly enhanced the antioxidant activity,68 while the introduction of an ethoxy carbonyl methyl had no influence on it. On the other hand, On the other hand, Kancheva et al.69 suggested that the substitution at the C-3 position did not have any effect either on the chain-breaking antioxidant activity or on the radical scavenging activity of the 7,8-dihydroxy- and 7,8- diacetoxy-4-methylcoumarins. Recently, Rodríguez et al.70 showed that the presence of the 3-aryl substituents is crucial for the increased activity and provides the most active radical scavengers.

CONCLUSION

Coumarin and coumarin-related compounds have proved for many years to have significant therapeutic potential. They come from a wide variety of natural sources and new coumarin derivatives are being discovered or synthesized on a regular basis. Coumarin is a simple molecule and many of its derivatives have been known for more than a century. However, their vital role in plant and animal biology has not been fully exploited. It is evident from the research described that coumarin and coumarin-related compounds are a plentiful source of potential drugs candidate in relation to its safety and efficacy. This review summarized the antioxidant activities of coumarin derivatives.

ACKNOWLEDGEMENT

This study was supported by the Universiti Kebangsaan Malaysia under the DIP-2012-02 Grant.

Notes

[1] Conflicts of interest CONFLICT OF INTEREST

The authors have declared that no competing interests exist.

ABBREVIATION USED

DPPH

2,2-diphenyl-1- picrylhydrazyl

HIV

human immunodeficiency virus

SAR

Structure activity relationships

IC50

The half maximal inhibitory concentration

L

Ligand; Chrome (Cr), Nickel (Ni), and Copper (Cu)

TNBS

Trinitrobenzene sulphonic acid (TNBS)

DNA

Deoxyribonucleic acid

X/XO

Xanthine oxidase

ROS

Reactive oxygen species

O2-

Superoxide.

REFERENCES

1. 

Abd El-All MM, Halawa AH, Hassan AH, El-Nassag MA, Abd El-Jaleel GE, et al. , authors. Synthesis and antioxidant activity of some derivatives of 2-(2-oxo-4-phenyl- 2H-chromen-7-yloxy)-acetohydrazide. J Atoms and Molecules. 2013;3:537–52

2. 

Al-Amiery A, Al-Majedy Y, Kadhum A , authors. Hydrogen Peroxide Scavenging Activity of Novel Coumarins Synthesized Using Different Approaches. PLoS ONE. 2015;10(7):e01321752015.

3. 

Al-Amiery AA, Al-Bayati R, Saour K, Radi M , authors. Cytotoxicity, Antioxidant and Antimicrobial activities of novel 2-quinolone derivatives derived from coumarins. Research on Chemical Intermediates. 2012;38(2):559–69

4. 

Al-Amiery AA, Al-Majedy Kadhum AAH, Mohamad A , authors. Novel macromolecules derived from coumarin: synthesis and antioxidant activity. Sci Rep. 2015;5:11825

5. 

Al-Amiery AA, Al-Majedy YK, Al-Duhaidahawi D, Kadhum AAH, Mohamad AB , authors. Green Antioxidants: Synthesis and Scavenging Activity of Coumarin-Thiadiazoles as Potential Antioxidants Complemented by Molecular Modeling Studies. Free Radicals and Antioxidants. 2016;6(2):173–7

6. 

Al-Amiery AA, Al-Majedy YK, Kadhum AA, Mohamad AB , authors. New coumarin derivative as an eco-friendly inhibitor of corrosion of mild steel in acid medium. Molecules. 2014;29;20(1):366–83

7. 

Al-Amiery AA, Al-Majedy YK, Kadhum AAH, Mohamad AB , authors. Synthesis of new coumarins complemented by quantum chemical studies. Research on Chemical Intermediates. 2016;42(4):3905–18

8. 

Al-Amiery AA, Kadhum AAH, Mohamad AA , authors. Antifungal Activities of New Coumarins. Molecules. 2012;17(5):5713–23

9. 

Al-Amiery AA, Kadhum AAH, Mohamad AB, Musa AY, Li CJ , authors. Electrochemical study on newly synthesized chlorocurcumin as an inhibitor for mild steel corrosion in hydrochloric acid. Materials. 2013;6(12):5466–77

10. 

Al-Amiery AA, Musa AY, Kadhum A, Mohamad A , authors. The use of umbelliferone in the synthesis of new heterocyclic compounds. Molecules. 2011;16(8):6833–43

11. 

Al-Ayed AS , author. Synthesis, Spectroscopy and Electrochemistry of New 3-(5-Aryl-4,5-Dihydro-1H-Pyrazol-3-yl)-4-Hydroxy-2H- Chromene-2-One 4, 5 as a Novel Class of Potential Anti- bacterial and Antioxidant Derivatives International Journal of Organic Chemistry. 2011;1(03):87–96

12. 

Al-Azawi F, Al-Baghdadi S, Mohamed A, Al-Amiery A, Abed T, et al. , authors. Synthesis, inhibition effects and quantum chemical studies of a novel coumarin derivative on the corrosion of mild steel in. Chemistry Central Journal. 2016;10(1):1–9

13. 

Al-Majedy Y, Al-Amiery A, Kadhum A , authors. Efficient catalyst one-pot synthesis of 3 7-(aryl)-10,10-dimethyl-10,11-dihydrochromeno[4,3-b] 4 chromene-6,8(7H,9H)-dione derivatives 5 complemented by antibacterial activity. BioMed Research International. 2016;2016:1–7

14. 

Al-Majedy Y, Kadhum K, Al-Amiery AAH , authors. A synthesis and characterization of Ahmed et al: Coumarins, Based Antioxidants some new 4-Hydroxy-coumarin derivatives. Molecules. 2014;19(8):11791–9

15. 

Al-Majedy YK, Al-Amiery AA, Kadhum AAH, Mohamad AB , authors. Antioxidant Activities of 4-Methylumbelliferone Derivatives. PLoS ONE. 2016;11(5):1–13

16. 

Al-Majedy YK, Al-Duhaidahawi D, Al-Azawi K, Al-Amiery AA, Kadhum AAH, et al. , authors. Coumarins as Potential Antioxidant Agents Complemented with Suggested Mechanisms and Approved by Molecular Modeling Studies. Molecules. 2016;21:135–45

17. 

Azizian J, Mohammadi A, Bidar I, Mirazaei P , authors. KAl (SO4)2•12H2O (alum) a reusable catalyst for the synthesis of some 4-substituted coumarins via Pechmann reaction under solvent-free conditions. Montash Chem. 2008;139(7):805–8

18. 

Čačić M, Pavić V, Molnar M, Šarkanj B, Has-Schön E , authors. Design and Synthesis of Some New 1,3,4-Thiadiazines with Coumarin Moieties and Their Antioxidative and Antifungal Activity. Journal of Molecules. 2014;19(1):1163–77

19. 

Cao G, Sofic E, Prior R , authors. Antioxidant capacity of tea and common vegetables. J Agric Food Chem. 1996;44(11):3426–31

20. 

Chang WS, Chiang HC , authors. Structure-activity relationship of coumarins in xanthine oxidase inhibition. Anticancer Res. 1995;15(15B):1969–73

21. 

Chavan S, Shivasankara K, Sivappaa R, Kalea R , authors. Zinc mediated transesterification of β-ketoesters and coumarin synthesis. Tetrahedron Lett. 2002;43:8583–6

22. 

Choudhary S, Kini SG, Mubeen M , authors. Antioxidant activity of novel coumarin substituted benzothiazole derivatives. Der Pharma Chemica. 2013;5(4):213–22

23. 

El-Agrody A, Abd El-Latif M, El-Hady N, Fakery A, Bedair A , authors. Hetero aromatization with 4-ydroxycoumarin Part II: Synthesis of some new pyrano[2,3-d] pyrimidines, [1,2,4]triazolo [1,5-c]pyrimidines and Pyrimido[1,6-b] [1,2,4]triazine derivatives. Molecules. 2001;6:519–520

24. 

El-Saghier A, Khodairy A, Khodiyar A , authors. New synthetic approaches to condensed and spirocoumarins: Coumarin-3-thiocarboxamide as building block for the the synthesis of condense and spirocoumarins. Phosphorus Sulphur Silicon. 2000. 160(1):p. 105–19. http://dx.doi.org/10.1080/10426500008043675.

25. 

Flašík R, Stankovičová H, Gáplovský A, Donovalová J , authors. Synthesis and study of novel coumarin derivatives potentially utilizable as memory media. Molecules. 2009;14(12):4838–4848

26. 

Foti M, Piattelli M, Baratta MT, Ruberto G , authors. Flavonoids, coumarins, and cinnamic acids as antioxidants in a micellar system. Structure-activity relationship. J Agric Food Chem. 1996;44(2):497–501

27. 

Gacche RN, Jadhav SG , authors. Antioxidant activities and cytotoxicity of selected coumarin derivatives :preliminary result of structure activity relationship study using computational tools. Journal of Experimental and Clinical Medicine. 2012;4(3):165–9

28. 

Garazd MM, Muzychka OV, Voyk AI, Nagorichna IV , authors. Ogorodniichuk AS. Modified coumarins. 27. Synthesis and antioxidant activity of 3-substituted 5,7-dihydroxy-4-methyl coumarins. Chem Nat Compd. 2007;43(1):19–23

29. 

Hamdi N, Puerta MC, Valerga P , authors. Synthesis, structure, antimicrobial and antioxidant investigations of dicoumarol and related compounds. European Journal of Medicinal Chemistry. 2008;43(11):2541–8

30. 

Hara K, Miyamoto K, Abe Y, Yanagida M , authors. Electron transport in coumarin-dyesensitized nanocrystalline TiO2 electrodes. J Phys Chem B. 2005;109(50):23776–8

31. 

Hashem FA , author. Investigation of free radical scavenging activity by ESR for coumarins isolated from Tecomaradicans. J Med Sci. 2007;7(6):1027–32

32. 

Heravi M, Sadjadi S, Oskooie H, Shoar R, Bamoharram F , authors. The synthesis of cou-marin-3-carboxylic acids and 3-acetyl-coumarin derivatives using heteropolyacids as heterogeneous and recyclable catalysts. Catal Commun. 2008;9(3):4704

33. 

Hung TT, Lu YJ, Liao WY, Huang CL , authors. Blue violet laser write-once optical disk with coumarin derivative recording layer. IEEE Trans Magn. 2007;43(2):867–9

34. 

Jayashree BS, Kumar A, Pai A , authors. synthesis characterization and antidiabetic evaluation novel coumarin analogues. Pharmacologyonline. 2011;3:1061–76

35. 

Kadhum A, Al-Amiery A, Musa A, Mohamad A , authors. The Antioxidant Activity of New Coumarin Derivatives. Int J Mol Sci. 2011;12(9):5747–61

36. 

Kadhum A, Mohamad A, Al-Amiery A, Takriff MS , authors. Antimicrobial and Antioxidant Activities of New Metal Complexes Derived from 3-Aminocoumarin. Journal of Molecules. 2011;16:6969–84

37. 

Kadhum AAH, Mohamad AB, Hammed LA, Al-Amiery AA, San NH, et al. , authors. Inhibition of mild steel corrosion in hydrochloric acid solution by new coumarin. Materials. 2014;7(6):4335–48

38. 

Kancheva VD, Saso L, Boranova PV, Khan A, Saroj MK, et al. , authors. Structure-activity relationship of dihydroxy-4- methylcoumarins as powerful antioxidants: correlation between experimental & theoretical data and synergistic effect. Biochimie. 2010;92:1089–100

39. 

Kennedy RO, Thornes RD , authors. Coumarins: Biology, Applications and Mode of ActionJohn Wiley and Sons; Chichester, England: 1997

40. 

Kotali A, Lafazanis I, Harris P , authors. Synthesis of 6,7-diacylcoumarins via the transformation of a hydroxy into a carbonyl group. Synth Commun. 2008;38(22):39964006

41. 

Kovalenko S, Bylov I, Sytnik K, Chernykh V, Bilokin Y , authors. A new pathway to 3- hetaryl2-oxo- 2H-chromenes: On the proposed mechanisms for the reaction of 3-carbamoyl-2-iminochromenes with dinucleophiles. Molecules. 2000;5(10):1146–1165

42. 

Lin S, Kuo P, Yang D , authors. Design and synthesis of a coumarin-based acidichromic colorant. Molecules. 2007;12(7):1316–24

43. 

Maja M, Čačić C , authors. Antioxidant activity of some (7-hydroxy-2-oxo-2H-chromen-4yl) acetic acid derivatives. J Food Sci Technol. 2012;4(1):54–63

44. 

Melagraki G, Afantitis A, Markopoulou OI, Detsi A, Koufaki M, et al. , authors. Synthesis and evaluation of the antioxidant and anti-inflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts. Eur J Med Chem. 2009;44(7):3020–6

45. 

Milan C, Maja M, Tomislav B, Nela D, Valentina R , authors. Design and synthesis of some thiazolidin-4-ones based on(7-hydroxy-2-oxo-2h-chromen-4-yl) acetic acid. Molecules. 2009;14(7):2501–13

46. 

Mukhatar S, Mujeebur RVP, Ansari WH, Lemiere G, de Groot A, et al. , authors. Bifunctional derivative of p,p’-dichlorochalcone. Part II. Synthesis of a novel compound 2-(2-Carboxymethylthio-2-(4-chlorophenyl)ethyl)-2-(4-chlorophenyl)- 4- thiazolidinone. Molecules. 1999;4(7):232–7

47. 

Murraya R, Jorge ZA , authors. Simple method for differentiating between angular and linear 5-methoxyfuranocoumarins. Phytochemistry. 1984;23(3):697–9

48. 

Natella F, Lorrain B, Prasad AK, Parmar VS, Saso L, et al. , authors. 4-methylcoumarins as antioxidants: scavenging of peroxyl radicals and inhibition of human low-density lipoprotein oxidation. Biochimie. 2010;92(9):1147–52

49. 

Nishiyama T, Ohnishi J, Hashiguchi Y , authors. Fused heterocyclic antioxidants: antioxidative activities of hydrocoumarins in a homogeneous solution. Bio sciBiotechnol-Biochem. 2001;65(5):1127–33

50. 

Nofal ZM, El-Zahar M, Abd El-Karim S , authors. Novel coumarin derivatives with expected biological activity. Molecules. 2000;5(2):99–113

51. 

Pedersen JZ, Oliveira C, Incerpi S, Kumar V, Fior AM, et al. , authors. Antioxidant activity of 4-methylcoumarins. J Pharm Pharmacol. 2007;59(12):1721–8

52. 

Rajasekaran S, Rao GK, Sanjay PN, Ranjan A , authors. Design, Synthesis, Antibacterial and in vitro Antioxidant activity of substituted 2 H - Benzopyran-2-one derivatives. International Journal of Chem Tech Research. 2011;3:555–9

53. 

Rajesh MP, Natvar P , authors. In vitro antioxidant activity of coumarin compounds by DPPH, Super oxide and nitric oxide free radical scavenging methods. Journal of Advanced Pharmacy Education & Research. 2011;1:52–68

54. 

Rajithaa B, Kumara VN, Someshwara P, Madhava JV, Reddy PN, et al. , authors. Dipyridine copper chloride catalyzed coumarin synthesis via Pechmann condensation under conventional heating and microwave irradiation. Arkivoc. 2006;12:2327

55. 

Ranganath YS, Babu VH, Sandeep G, Parameshwar R , authors. Synthesis and evaluation of some novel furocoumarin derivatives for radical scavenging profile and cytotoxic studies. J Chem Pharm Res. 2011;3:62–8

56. 

Ravi SK , author. International Journal of Biological & Pharmaceutical Research. 2013;4:862–71

57. 

Ray D, Bharadwaj PK , authors. A Coumarin-derived fluorescence probe selective for magnesium. Inorg Chem. 2008;47(7):2252–4

58. 

Rodriguez SA, Nazareno MA, Baumgartner MT , authors. Effect of different C3-aryl sub-stituents on the antioxidant activity of 4- hydroxycoumarin derivatives. Bioorg Med Chem.

59. 

Rositca DN, Vayssilov GN, Rodios N, Bojilova A , authors. Regio- and Stereoselective (2 + 2) Photodimerization of 3-Substituted 2-Alkoxy-2-oxo-2H-1,2-benzoxaphosphorines. Molecules. 2002;7(5):420–432

60. 

Roussak M, Kontogiorgis CH, Litina A, Hamilakis D, Detsi S , authors. A novel synthesis of 3-aryl coumarins and evaluation of their antioxidant and lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2010;20(13):3889–92

61. 

Satyanarayan VS, Sreevani P, Sivakumar A , authors. Synthesis and antimicrobial activity of new Schiff bases containing coumarin moiety and their spectral characterization. Arkivoc. 2008;17:221–233

62. 

Singh OM, Devi NS, Thokchom DS, Sharma GJ , authors. Novel 3-alkanoyl/aroyl/ hetero-aroyl-2H- chromene-2-thiones: Synthesis and evaluation of their antioxidant activities. Eur J Med Chem. 2010;45(6):2250–7

63. 

Smitha G, Sanjeeva R , authors. ZrCl4-catalyzed Pechmann reaction: Synthesis of coumarins under solvent-free conditions. Synth. Commun. 2004;34(21):3997–4003

64. 

Stanchev S, Hadjimitova V, Traykov T, Boyanov T, Manolov I , authors. Investigation of the antioxidant properties of some new 4-hydroxycoumarin derivatives. Eur J Med Chem. 2009;44:3077–82

65. 

Symeonidis T, Chamilos M, Hadjipavlou-Litina DJ, Kallitsakis M, Litinas KE , authors. Bioorganic & Medicinal Chemistry Letters. 2009;19:1139–42

66. 

Vazquez-Rodriguez S, Matos MJ, Guí-ez RF, Maya JD, Lapier M, et al. , authors. Coumarin-chalcone derivatives as potential antitrypanosomal and antioxidant compounds. ECSOC. 2012;16:1–14

67. 

Witaicenis A, Seito LN , authors. Di Stasi LC Intestinal anti- inflammatory activity of esculetin and 4-methylesculetin in the trinitro benzene sulphonic acid model of rat colitis. ChemBiol Interact. 2010;186(2):211–218

68. 

Yang J, Liu GY, Dai F, Cao XY, Kang YF, et al. , authors. Synthesis and biological evaluation of hydroxylated 3-phenylcoumarins as antioxidants and antiproliferative agents. Bioorg Med Chem Lett. 2011;21(49-52):6420–5

69. 

Yavari I, Hekmat-Shoar R, Zonouzi A , authors. A new and efficient route to 4-carboxymethylcoumarins mediated by vinyl triphenylphosphonium salt. Tetrahedron Lett. 1998;39(16):2391–2

70. 

Zabradnik M , author. The Production and Application of Fluorescent Brightening AgentsJohn Wiley and Sons; New York, NY, USA: 1992

SUMMARY

  • Coumarins have significant therapeutic potential. Coumarins are known for more than a century. Coumarins are a plentiful source of potential drugs candidate in relation to thier safety and efficacy. This review summarized the antioxidant activities of some synthesized coumarins.

AUTHOR PROFILE

Ahmed Al-Amiery: (h-index= 17), is an Professor at University of Technology. Dr. Al-Amiery has over 100 scientific papers and projects either presented or published and international patent. He is an internationally expert in many areas of applied chemistry. Recent publications include a paper on the use of novel coumarin derivatives as corrosion inhibitors. Al-Amiery has Post-doctoral from Department of Chemical and Process Engineering Universiti Kebangsaan Malaysia. Dr. Al-Amiery has been awarded the Medal of scientific excellence (2014), and also Hold Science Day Awards from the Ministry of Higher Education and Scientific Research for four consecutive years (2010-2015). Al-Amiery selected for the Who’s Who for International Executives 2015. Al-Amiery is a TWAS-Young Affiliates.