Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

ISSN:0975-1459

Chalcone: A Versatile Molecule

Chetana B. Patil*, S. K. Mahajan, Suvarna A. Katti
Department of Pharmaceutical Chemistry, M. G. V’s Pharmacy College, Panchavati, Nashik-422003,
Maharashtra, India.

________________________________________________________________________

ABSTRACT:
Chalcones are 1,3-diphenyl-2-propene-1-one, in which two aromatic rings are linked by a three
carbon α,β-unsaturated carbonyl system.These are abundant in edible plants and are considered to
be precursors of flavonoids and isoflavonoids. The aim of this review to give summary of
methods for synthesis of chalcones, its chemical modifications to flavonoids, flavanone, pyrazoles,
oxazoles, pyrimidines. This article also highlights antioxidant potential of chalcone, mechanism of
antioxidant activity of chalcones and structure activity relationship of chalcone derivatives for
antioxidant ability and different methods to evaluate antioxidant activity of chalcone, anti-
inflammatory, cytotoxic and antihyperglycemic activity of chalcones is also discussed in this review
article.

KEYWORDS: Antioxidant, chalcone, Claisen-schimdt reaction, MOM (methoxymethyl)-protected

benzaldehyde
________________________________________________________________________

INTRODUCTION [1] Chalcones are synthesized by

Chalcones are 1,3-diphenyl-2-propene- claisen-schmidt condensation of
1-one, in which two aromatic rings aldehyde and ketone by base
are linked by a three carbon α, β- catalyzed or acid catalyzed followed
unsaturated carbonyl system as, by dehydration to yield chalcones.
O

6 2'
5 1 3 1'
3' A. Base catalyzed reaction [2][3][4]
1 2
A B The main method for the
4 2 6' 4' synthesis of chalcones is the classical
3 5' Claisen-Schmidt condensation in the
Chalcone presence of aqueous alkaline bases.

These are abundant in edible plants

and are considered to be precursors Procedure [2]
of flavonoids and isoflavonoids. Place a solution of 22g of sodium
Chalcones possess conjugated hydroxide in 200ml of water and
double bonds and a completely 100g (122.5ml) of rectified spirit in a
delocalized Π-electron system on both 500ml bolt-head flask provided with
benzene rings. Molecules possessing a mechanical Stirrer. Immerse the
such system have flask in a bath of crushed ice, pour
relatively low redox potentials and in 52g (0.43mol) of freshly distilled
have a greater probability of acetophenone, start the stirrer and
undergoing electron transfer reactions. then add 46g (44ml, 0.43mol) of
1. Methods for synthesis of chalcones: pure benzaldehyde.
_________________________________
*For Correspondence
Email: [email protected]

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 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

Mechanism[2]

Ar H H2C Ar' Ar Ar'

+ NaOH

O O O O

Aldehyde Ketone

+ H

H H

Ar Ar' Ar Ar'
-H2O

O OH O
Chalcone

Keep the temperature of the mixture to litmus and then with 20ml of ice-
at about 250C (the limits are 15- cold rectified spirit. The crude
300C) and stir vigorously until the chalcone after drying in the air
mixture is so thick that stirring is no weighs 88g and melts at 50-540C.
longer effective (2-3 hr). Remove the Recrystallized from rectified spirit
stirrer and leave the reaction mixture warmed to 500C (about 5ml per g).
in an ice chest or refrigerator The yield of pure
overnight. Filter the product with benzylideneacetophenone (a pale
0
suction on a buchner funnel or a yellow solid) mp 56-57 C, is 77g
sintered glass funnel, wash with cold (85%).This substance should be
water until the washings are neutral handled with great care since it acts
as a skin irritant.

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 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

B. Acid catalyzed reaction:

Mechanism[5]

O OH OH

CH3 + H CH3 CH3

Acetophenone

OH

CH2
+ H

O OH OH

H + H H H

Benzaldehyde

H OH
OH
O H
OH
CH2 H
+

O H

+ H

OH

O H O H H
H

H
OH OH2
H H

- H3O

Chalcone

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 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

Procedure [6] It is necessary to use protective

group for the preparation of the
To a stirred mixture of acetophenone hydroxy chalcones under basic
(0.01mol) and benzaldehyde conditions. By using SOCl2 as a
(0.01mol) in absolute ethanol (5ml), convenient alternative to the gaseous
add thionyl chloride (0.05ml) HCl in the aldol condensation.
dropwise and continue stirring for
two hour at room temperature. Allow C. Methods for sy nthesis o f
to stand reaction mixture for 12hr. chalcones having hydroxy
Precipitate the reaction mixture by substituted aldehyde precursors[7]
addition of water. Filter the product, The chalcone derivatives are prepare
wash with cold ethanol. The yield of through base-catalyzed claisen-schimdt
pure benzylideneacetophenone (a pale condensation of MOM-protected
yellow solid) mp 56-570C, is 77.0g benzaldehydes with para- substituted
(85%). acetophenones followed by acid
catalyzed hydrolysis. In the reactions,
the MOM- protected benzaldehydes
In the presence of SOCl2/EtOH as a are used instead of non-protected
catalyst various substituted chalcones dihydroxylated ones, because the
are synthesized by aldol condensation. procedure with the free
The HCl is generate in situ by the dihydroxylated benzaldehydes required
reaction of SOCl2 with absolute long reaction time (more than one
ethanol. day) and relatively high temperature
(above 600C) which resulted in poor
The aldol reaction is perform also yields with unknown degraded
under acidic medium, using HCl, products.
BF3, B2O3, p-toluene sulfonic acid,
etc. The most common method The MOM group is proven to be the
applies ethanol saturated with HCl. best choice. The MOM-protected
The yields are low and vary between benzaldehydes which are readily
10% - 40%. According to the prepared by treating the corresponding
literature data the presence of benzaldehydes with MOMCl in basic
hydroxyl substituents in the aromatic condition (K2CO3/acetone), are
aldehyde hinders the basic catalyze successfully converted to the chalcone
aldol reaction. The reason behind that derivatives with diverse substitution
is the fact that the basic catalysts patterns of two hydroxyl groups on
decrease the activity of the aldehyde benzaldehyde origin ring B. Now the
component because of delocalization hydroxyl protected chalcones are
of the anion, which is illustrated deprotect in situ by acid hydrolysis
below, to provide the desired final chalcone
derivatives in good yields (>70%)
with some exception.

O B O O
HO O O
H BH H H

Anion delocalization of the aldehydic component

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 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

The relatively low yields for some 5 with 1N aqueous NaOH solution.
products containing para- hydroxyl Extract the aqueous solution with
acetophenone are consider probably EtoAc (20 ml x 3). Wash the organic
due to the phenoxide ion formation layer with water (20 ml x 2) and brine
from the acetophenone in the presence (20ml), dry over anhydrous MgSO4
of strong and excess amount of base. and evaporate to give a crude solid.
The double bond geometry of all Purify resulting product by column
chalcones is determine as E form the chromatography, elute with hexane-
characteristic coupling constants ethyl acetate co-solvent to afford a
between α and β protons. solid.

I. Hydrox y b enzaldehydes protect ed D. Microwave assisted synthesis[8]

by MOM[7] The Claisen–Schmidt condensation
Cool the solution of hydroxy stays the most common method in
benzaldehyde (21.17 mmol) and homogeneous phase or in interfacial
K2CO3 (217.20 mmol) in acetone solid-liquid conditions using barium
(100ml) to 0 0C under Argon hydroxide catalyst (C-200).
atmosphere and add Unfortunately 2’-hydroxychalcones
methoxymethylchloride (MOM-Cl, always cyclized to flavanones. One
93.65 mmol) dropwise. Stir the synthetic pathway to avoid this
resulting mixture at room temperature undesirable reaction is using
for 6-10 hr. Dilute the reaction protective group or the Friedel–Crafts
mixture with water (100ml) and reaction of phenols with acyl halides.
extract with ethyl acetate (50ml x 3). This method request long reaction
Wash organic layer with water and time and anhydrous conditions which
brine, dry over anhydrous MgSO4 limits the scope of its application.
and evaporate to dryness to yield Convenient reaction procedure for the
crude MOM- protected benzaldehyde. synthesis of 2’-hydroxychalcones with
Purify by silica gel column very good yields without formation of
chromatography to give analytically by-products. By applying successful
pure compounds (90-99%). microwave irradiation for the
preparation of target molecules . The
II. Gener al syntheti c procedure for reaction took place in well closed
the preparation o f pressure tube for 2 min with high
[7]
dihydroxychalcones yields. It is noteworthy to mention that
To a solution of MOM-protected to carry out the reaction in an open
benzaldehydes (0.9 mmol) and vessel failed. A mixture of two
acetophenone (10mmol) in ethanol products (3 and 4) and starting
(10ml), add 5% aqueous NaOH compounds was obtained in this case.
(1.1mmol, 0.5ml). Stir the reaction Obviously, the well closed tube
mixture at room temperature for 1-2 affords to reach temperatures much
hr. Moniter the reaction, add 10% higher than boiling point of ethanol.
HCl (1ml) and continue stirring for The measured temperature in the
30 min at 600C to deprotect the reaction tube immediately after the
MOM groups. Dilute the mixture irradiation was 1320C.
with water (20 ml) and adjust pH to

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R1
R2 CHO
O O
O
R3
2 R1 R1
CH3
R2 R2
KOH/EtOH uW or O
OH 1320C OH
1 R3 4 R3
3

2. Chemical modifications of dry with MgSO4 anhydrous.

chalcones: Evaporate the solvent in vaccuo.

I. Flavonoids[9] Purify the residue by chromatographic

Flavonoids or bioflavonoids are a column (SiO2, petroleum
ubiquitous group of polyphenolic ethermethylene dichloride (0-30%).
substances which are present in most
plants. Flavonoids have been shown [II] S ynthesis of 3, 5-d iphenyl-4, 5-
to have antibacterial, anti- dihydro-1, 2-oxazole[11]
inflammatory, antiallergic, Dissolve anhydrous sodium acetate
antimutagenic, antiviral, antineoplastic, (0.02 mol) in hot acetic acid. Add
anti-thrombotic and vasodilatory hydroxylamine hydrochloride (0.01
activity. The potent antioxidant mol) in absolute alcohol (10ml) to
activity of flavonoids their ability to the solution of chalcone in ethanol.
scavenge hydroxyl radicals, Transfer the solution of sodium
superoxide anions and lipid peroxy acetate in acetic acid to this reaction
radicals may be the most important mixture and reflux for 10 hr. Pour
function of flavonoids. the reaction mixture into ice cold
The structural components common to water, Filter the product and
these molecules include two benzene recrystallize with ethanol.
rings on either side of a 3-carbon
ring. Multiple combinations of [III] Synthesis of 1, 3, 5 -triphenyl-4,
hydroxyl groups, sugars, oxygen, and 5- dihydro-1H-pyrazole[11]
methyl groups attached to these To a mixture of chalcone and phenyl
structures create the various classes hydrazine (0.01 mol) in absolute
of flavonoids; flavonols, flavanones, alcohol, add catalytic amount of
flavones, flavan-3-ols (catechins), pyridine and reflux reaction mixture
anthocynins and isoflavones. for 5-8 hr. Cool the reaction mixture,
Pour slowly into crushed ice with
General procedure for t he synthesis stirring. Filter the solid product. Dry
of flavanone[10] and recrystallize with ethanol.
Reflux a solution of the 2’-
hydroxychalcone (1 equiv) in AcOH 3. Pharmacological profile:
glacial (25.0 ml/mmol of 2’- I Antioxidants[9]
hydroxychalcone) for 72 hr. Pour the Free radicals, including the
mixture into water. Extract with superoxide radical (O2.-), hydroxyl
EtOAC (3x25.0ml). Wash the organic radical (.OH), hydrogen peroxide
layer with brine until neutrality and (H2O2), and lipid peroxide radicals

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 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

have been implicated in a number groups of chalcones. The ortho (i.e.

of disease processes, including catechol structure) and para-
asthma, cancer, cardiovascular dihydroxylated benzene ring system
disease, cataracts, diabetes, are generally known to delocalize
gastrointestinal inflammatory electrons. As the phenoxy radicals
diseases, liver disease, macular occurring at the ortho- (i.e. catechol
degeneration, periodontal disease and structure) or para-dihydroxylated
other inflammatory processes. These benzene ring system are much more
radical oxygen species (ROS) are readily converted to a fairly stable
produced as a normal consequence of semiquinone radicals while, meta
biochemical processes in the body dihydroxylated benzene ring system is
and as a result of increased exposure comparatively less efficient to
to environmental and/or dietary delocalize electrons as the phenoxy
xenobiotics. radicals occurring at the meta
dihydroxylated ring system is
Antioxidants are the agents, which converted to quinone structure which
can inhibit or delay the oxidation of is not much stable.
an oxidisable substrate in a chain
reaction.
OH RH O O
R
R
Chalcones belongs to the largest class OH O H O

of plant secondary metabolites.

Which, in many cases, serve in plant ortho-semiquinone ortho-quinone
ortho-substituted
defense mechanisms to counteract
reactive oxygen species (ROS) in OH O
O
RH
order to survive and prevent R

molecular damage and damage by

microorganisms, insects, and
O
herbivores. They are known to OH
H R
O

possess antioxidant character at para-substituted para-semiquinone para-quinone

various extents. The antioxidant
activity of natural compounds like OH
R RH O

chalconoids is related to a number of No further

different mechanisms such as free OH
reaction
OH
radical scavenging, hydrogen donation
singlet oxygen quenching, metal ion meta-substituted

chelation and acting as a substrate for

free radicals such as superoxide and Proposed ra tionale for stro ng
hydroxide. activity of ortho- and para
dihydroxylated c halcones vs meta-
Mechanism o f antioxidant activity dihydroxylated ones.
of chalcones[7]
When the chalcone molecules react Structure Activity Relationship[7]
with the radicals, they are readily It is proven as, the chalcone
converted to the phenoxy radicals due compounds with the ortho- (i.e. 2’,
to the high reactivity of hydroxyl 3’- and 3’,4’-) and para- (i.e. .2,5’-)

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 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

substitution patterns show an excellent peroxynitrite, a potent oxidizing

antioxidant activities (80-90% of molecule that contributes to tissue
control at the concentration of 50µM) injury during inflammatory responses.
which are comparable to those of Nitric oxide is generated from L-
ascorbic acid and α-tocopherol as arginine by nitric oxide synthase
positive reference materials. (NOS).

On the contrary, the compounds with Compounds that inhibit excess

meta- (i.e. 2’,4’-, 3’,5’-) substitution production of NO by macrophages
pattern demonstrate very dramatic might be of benefit for the prevention
decrease in activities which are and treatment of autoimmune
around 25% of the control even at diseases, septic shock and different
the concentration of 200µM (IC50 > inflammatory pathologies.
200µM).
Chalcones with substituents that
Thus, it indicate that the substitution increase the electronic density of the
patterns of two hydroxyl groups on B-ring, such as methoxy, butoxy or
ring B are very important structural dimethylamine groups, did not show
factors for their radical scavenging significant activity in the inhibition of
activity enhancement. the nitrite production.

The para substituted group exhibited Trimethoxy chalcone derivatives with

better free radical scavenging activities fluoro substitution at C4’ are better
than ortho substituted system. inhibitors of nitrite production.
Trifluoromethyl group at C2’ in
The variation of the substituents at dimethoxy chalcones as well as
para position of ring A makes no trimethoxy chalcones possess very
distinctive differences in activities. potent inhibition of nitrite
This observation indicates that the accumulation.
electronic effects of para- subsistent
of the phenyl ring-A does not affect Trifluoromethyl group at C3’ or C4’
the radical scavenging activity and in dimethoxy chalcone as well as
therefore are unlikely to contribute to trimethoxy chalcone possess less
variation of antioxidant activities. activity than when it is at C2’.

II Antiinflammatory[12] III Cytotoxic activity[13]

Activated macrophages play a key Mannich bases of phenolic
role in inflammatory responses and azobenzenes demonstrated cytotoxic
release a variety of mediators, activity, and various mannich bases
including nitric oxide (NO). NO is a analogs of chalcones exhibited potent
potent vasodilator that facilitates cytotoxicity against murine P338 and
leukocyte migration and formation of L1210 leukemia cells as well as
edema, as well as leukocyte activity several human tumor cell lines.
and cytokine production. Mannich bases of heterocyclic
NO can also react with chalcones are evaluated for cytotoxic
superoxide anion to form activity against four human cancer

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cell lines (PC-3, MCF-7, KB and glucose lowering activity. Compounds

KB-VIN). Mannich base of chalcone vicinally deoxygenated as dimethoxy
with morpholine substitution at C3 or and methylenedioxy substitution
C5 and pyridyl or phenyl at C2 showed the best antihyperglycemic
substitution are found to possess good activity when compared to the
cytotoxic activity. corresponding monomethoxy
compounds. Compounds containing
IV Hypoglycemic activity[14] propanolamine chain at para position
Non-insulin dependent diabetes showed significant activity as
mellitus (NIDDM, type-II diabetes) is compared to meta and ortho
a chronic metabolic disease substituted compounds.
characterized by insulin resistance,
hyperglycemia and hyperinsulinaemia. V Antihepatotoxic activity[15]
The disease is often associated with Silymarin isolated from seeds of
obesity, dyslipidemia and hypertension silybum marianum commonly known
leading to cardiovascular risks. as Milk Thistle has been used as a
potent Antihepatotoxic agent against a
β3-adrenergic receptors (β3-AR) are variety of toxicants. It is a mixture
found on the cell surface of both of three isomers namely, silybin (1),
white adipose (WAT) and brown silydianin (2) and silychristin (3).
adipose tissue (BAT) where their Silybin is the most active component
stimulation promotes lipolysis and containing 1,4-dioxane ring system,
thermogenesis respectively. BAT also whereas other isomers do not possess
plays an important role in the 1,4-dioxane ring, and thus do not
maintenance of glucose homeostasis; display significant activity.
hence β3-AR agonists are useful for
treating diabetes as well as obesity. Chalcone derivatives possessing 1,4-
The aryloxypropanolamines were first dioxane ring system exhibiting
described as β3-AR agonists. antihepatotoxic activity. The potent
compounds possess 2-hydroxy methyl
Chalcones with proper substitution group at position 2 of the dioxane
have recently been isolated from ring of chalcone derivatives, which
Broussonetia papyrifera known to has also indicated that the presence
selectively inhibit enzymes like of hydroxy methyl group at position
protein tyrosine phosphatase 1B 2 in dioxane ring possesses a
(PTP1B) and aldose reductase. Their significant role in exhibiting the
antioxidant property attracted to antihepatotoxic activity. This is in
explore hybrid structures as accordance with the view that silybin
antihyperglycemic agents, because too possess the same group at the
oxidative stress also plays an same position.
important role in diabetic patients
leading to vascular complications. The substitution in the aromatic ring
of chalcones have no significant role
3, 4-Dimethoxy compound displayed in exhibiting antihepatotoxic activity.
significant antihyperglycemic effect.
Mono methoxy series showed blood

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VI Antimicrobial activity[16] to be the least active. Compound ,

Compounds with electron releasing containing triazole and chloro
groups such as methoxy and hydroxyl substituents, was found to be the
showed better antibacterial activity most potent antiplasmodial derivative
than the others not having such evaluated, suggesting that small
groups. Compounds having lipophilic groups containing single or
pharmacophores such as chloro, multiple nitrogen can enhance
dichloro and fluoro groups have antimalarial activity in vitro.
exhibited more antifungal activity on
all the three fungi than the others. In vitro antiplasmodial results of 4-
Chalcone derivatives with these chloro, 4-methoxy and 3,4,5-
substituents showing greater trimethoxy series suggested that small
antimicrobial activity. or medium sized but highly lipophilic
groups containing multiple nitrogen or
VII Antimalerial activity[17][18][19] amine in acetophenone moiety impart
Antimalarial property of some antiplasmodial potential. Such
chalcone derivatives is derived from compounds may provide additional
their ability to inhibit the parasitic hydrogen bonding with histidine
enzyme, cysteine protease. The residue present at the active site of
enzyme catabolizes globin into small the enzyme, cysteine protease. This is
peptides within the acidic food the first report in which chalcones
vacuole of the intra-erythrocytic containing small highly polar,
malaria parasite. Without cysteine lipophilic cyclic amines are showing
protease action osmotic swelling antimalarial potential.
occurs, food vacuolar functions are
impaired, and parasite death ensues. VIII Antileishmanial activity[20]
Malaria blood stage cysteine protease Conventional structure activity
as the most likely target enzyme of relationships show that antileishmanial
chalcones. The chalcones are activity is favoured by chalcones with
conjugates of α, ß-unsaturated ketones more hydrophilic character, with the
that assume linear or near planar most active members found among
structure. This structure is stable in 40-hydroxychalcones. The good
acidic food vacuolar environment antileishmanial activities of the
where malarial cysteine protease acts, naphthalenyl and pyridinyl derivatives
and structural conformation may fit suggest that considerable tolerance for
well into the long cleft of the active the size of ring A exists.
site of the enzyme.
IX Tyrosinase inhibitors[21] [22]
The chloro-series compounds showed Tyrosinase (monophenol
marked antiplasmodial activity. monooxygenase, E: C: 1.14. 18.1), also
Compound , a triazole substituted known as polyphenol oxidase), is a
chalcone was found to be the most copper-containing enzyme widely
effective against the parasites, and distributed in nature. It catalyzes two
pyrrole and benzotriazole showed reactions involving molecular oxygen
comparable activities. The morpholine in the melanin biosynthesis pathway:
substituents in chloroseries was found the hydroxylation of monophenols to

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 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

o-phenols (monophenolase activity), [7] Beom-Tae Kim, Kwang-Joong O, Jae-Chul

and the oxidation of the o-phenols to Chun, and Ki-Jun Hwang, Bull. Korean
Chem.Soc. 2008, Vol. 29, No. 6
o-quinones (diphenolase activity). [8] Edmont V. Stoyanov,a,* Yves Champavier,b
These quinones are highly reactive Alain Simonc and Jean-Philippe Baslyc,
and tend to polymerize spontaneously Bioorganic & Medicinal Chemistry Letters 12
to form brown pigments of high (2002) 2685–2687
molecular weight (melanins), which [9] Alan L. Miller, ND, Alternative Medicine
Review, volume 1, Number 2, 1996, 103-111
determine the color of mammalian [10] Mauricio Cabrera, Macarena Simoens,
skin and hair. Quinones can also Gabriela Falchi, M. Laura Lavaggi, Oscar E.
react with amino acids and proteins Piro, Eduardo E. Castellano, Anabel Vidal,
and thus enhance the development of Amaia Azqueta, Antonio Monge, Adela
brown color. The inhibitory activity Lopez de Cerain, Gabriel Sagrera, Gustavo
Seoane, Hugo Cerecetto and Mercedes
of a series of chalcones was set Gonzalez, Bioorganic & Medicinal Chemistry
against their structure and their 15 (2007) 3356-3367
antioxidant potency (which can [11] Archita Bapna, Swati Ojha & G. L.
contribute to prevent pigmentation Talesara, Indian Journal of Chemistry,
resulting from nonenzymatic vol.47B, July 2008, pp.1096-1107
[12] Javier Rojas, Miguel Paya´ ,Jose´ N.
oxidation). The position of the Dominguez and M. Luisa Ferra´ ndiz,
hydroxyl groups attached to the A Bioorganic & Medicinal Chemistry Letters 12
and B aromatic rings is of major (2002) 1951–1954
importance, while hydroxylation on [13] M. Vijaya Bhaskar Reddy , Chung-Ren Su ,
ring B contributes markedly more to Wen-Fei Chiou , Yi-Nan Liu , Rosemary Yin-
Hwa Chen ,Kenneth F. Bastow , Kuo-Hsiung
inhibition than when it is on ring A. Lee , Tian-Shung Wua, Reddy, M. V. B. et al.,
Butein, an effective tyrosinase Bioorg. Med. Chem. (2008),
inhibitor, was also able to delay doi:10.1016/j.bmc.2008.06.018
linoleic acid auto-oxidation, as shown [14] M. Satyanarayana, Priti Tiwari,
by conjugated diene (CD) formation. Brajendra K. Tripathi, A. K. Srivastava
And Ram Pratap, Bioorganic & Medicinal
The OH in position 4 (ring B) was Chemistry 12 (2004) 883–889
the major factor affecting potency. [15] SHAH ALAM KHAN*, BAHAR
AHMED AND TANVEER ALAM, Pak. J.
References: Pharm. Sci., 2006, Vol.19(4), 290-294
[1] Abdur RAHMAN, Rumana QURESHI, [16] Y. RAJENDRA PRASAD, P. RAVI
Mehvish KIRAN, Farzana Latif ANSARI, Turk KUMAR and B. RAMESH, Int. J. Chem. Sci.:
J Chem., 31 (2007) , 25 – 34. 5(2), 2007, 542-548
[2] Vogel’s Textbook of practical organic [17] Nidhi Mishra , Preeti Arora , Brajesh
chemistry, fifth edition, by Funiss B. S., Kumar , Lokesh C. Mishra , Amit
Hannford A. J., Smith P. W. G., Tatchell A. Bhattacharya , Satish K. Awasthi , Virendra K.
R., (2004), 1032-1035. Bhasin , European Journal of Medicinal
[3] Advanced Organic Chemistry, Reactions, Chemistry 43 (2008) 1530e1535
Mechanisms, and Structure, Fourth edition, [18] Alain Valla , Benoist Valla , Dominique
by Jerry March, A Wiley-Interscience Cartier , Régis Le Guillou , Roger Labia,
Publication 939-943 Loic Florent , Sébastien Charneau , Joseph
[4] Morrison and Boyd, Organic Chemistry, Schrevel , Pierre Potier European Journal of
sixth edition, 2004, 971-990, 997-820. Medicinal Chemistry 41 (2006) 142–146
[5] Mukherji S. M., Singh S. P., Kapoor R. [19] Mao Sheng CHENG, Rong Shi LI,
P., Organic Chemistry, vol.II, International George KENYON Chinese Chemical Letters
(P) Limited, Publishers, 2003, 586-587. Vol. 11, No. 10, pp. 851−854, 2000
[6] Ognyan Petrov , Yordanka Ivanova, Mariana [20] Mei Liu, Prapon Wilairat, Simon L. Croft,
Gerova, Catalysis Communications 9 (2008) Bioorganic & Medicinal Chemistry 11 (2003)
315–316 2729–2738

21
 Chetana B Patil et al /J. Pharm. Sci. & Res. Vol.1(3), 2009, 11-22.

[21] Ohad Nerya , Ramadan Musa , Soliman [22] Nishida Jun, Gao Hong and Kawabata
Khatib , Snait Tamir , Jacob Vaya, Jun, Bioorganic & Medicinal Chemistry
Phytochemistry 65 (2004) 1389–1395 15 (2007) 2396-2402

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