Synthesis and Pharmacological Evaluation of
Flavonoids
M. Pharm Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore – 560 041
By
Mr. SAUMIK DEY B. Pharm.
Under the Guidance of
Mr. GURUBASAVARAJA SWAMY.P.M.
Assistant Professor
Department of Pharmaceutical Chemistry,
Acharya & B.M. Reddy College of Pharmacy,
Soldevanahalli, Chikkabanavara,
Bangalore - 560090
1
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
Mr SAUMIK DEY
1
Name
of
the
candidate
and C/O DR DIVAKAR GOLI,
Acharya& B.M. Reddy college of Pharmacy,
address
Soladevanahalli,Hesaraghatta main road,
Bangalore-560090.
ACHARYA & B.M. REDDY COLLEGE OF
2
Name of the institution
PHARMACY.
Soldevanahalli, Chikkabanavara post,
Hesaraghatta main road,
Bangalore – 560090.
Office: 080-65650815. Fax :080-28393541.
MASTER OF PHARMACY
3
Course of study and subject
(PHARMACEUTICAL CHEMISTRY)
4
Date of the admission
1st December 2010
5
Title
of
the
topic:
“SYNTHESIS
EVALUATION OF FLAVONOIDS.”
2
AND
PHARMACOLOGICAL
6.0 Brief resume of the intended work
6.1 Need for study:
Flavonoids represents an important group of common naturally occurring
polyphenolic compounds present in the plant kingdom.Generally they occur as plant pigments
in a broad range of fruits and vegetables as well as in tea,red wine, coffee, and beer. These
compounds constitute one of the main classes of secondary metabolites. They display a large
range of structures and are responsible for a major organoleptic characteristic of plant derived
foods and beverages particularly colour and taste properties of fruit and vegetables.
These flavonoids drew later attention from researchers with discovery of French
paradox i.e. the decrease incidents of cardiovascular diseases observed in the Mediterranean
population.1
Flavonoids can be classified as aglycones, glycosides, and methylated derivatives. In
plant flavonoids aglycones occurs in various structural forms. All the derivatives contain 15
carbon atoms in their basic nucleus two six membered rings linked 3 carbon atom
The 6 membered rings condensed with benzene ring in their ɣ-pyrone (flavones ,
flavonols or its dihydro derivatives {flavonones and flavon-3-ols}). Based on the benzoid
substituents the flavonoids are divided into two classes flavonoids and isoflavonoids which
are further subdivided into dihydrochalcone ,flavanones , isoflavonones and aurones.
3
O
O
Chalcone
Dihydrochalcone
O
O
O
O
Isoflavones
Flavones
O
O
OH
O
O
Aurones
Flavonol
4
O
OH
OH
O
Flavanonol
3-Flavanol
The word flavonoids comes from the latin word flavus which means yellow , however some
flavonoids are red , blue or purple in colour. Most of the flavonoids are isolated from natural
sources and all above sets different classes of flavonoids or isolated from the same.
Classification of Flavonoids:1
Chemical Class
Flavonol
Examples
Major dietary source
Quercetin, rutin , myricetin, Tea, red wine, apple, tomato ,
kaempferol
cherry and onion
Flavanols
Catechin , gallocatechin
Tea and apple
Flavones
Apigenin , chrysin , luteolin
Thyme and parsley
Isoflavones
Genistein,
Soyabean and other legumes
glyciteinformononetein,
daidzein
Flavanones
Hesperidin, narigenin
Grapefruit and orange
Flavanonols
Taxifolin
Lemon and sour orange
5
Marketed Drug Containing Flavonoids:
OH
OH
OH
OH
HO
HO
O
O
OH
OH
OH
OH
O
OH
O
Quercetin
OH
OH
Gallocatechin gallate
Rutin
These are the few flavonoid containing drugs which are marketed namely quercetin,
gallocatechin and rutin which are used as circulatory health enhancer, antioxidant and
dietary supplement respectively.26
Based on the above findings of flavonoids in nature many researchers
particularly the medicinal chemists discovered the route for the synthesis of the main
flavonoids. The following are some of the methods for the synthesis of various flavonoids.
As a flavonoids gamed interest because then broad biological and pharmacological
activities, the flavonoids have been reported to exact multiole biological effects including
as a cardio protective agents1, antimicrobial agents2,3,4,10, antioxidants3,5 hypolipidemia6, pglycoprotein
inhibitors7,
vasodilator8,
antiinflammatory9,
anticoagulating
agent11,
antiproliferative12.
Keeping in view of biological importance of flavonoids and their
6
derivatives, we plan to carry out a research work on the synthesis and pharmacological
evaluation of substituted flavonoids. These flavonoids can be synthesized from chalcones
to obtain potent biomolecule.
6.4 Review of literature
1.
Mukesh Nandave, S.K. Ojha, D.S.Arya et al,1 carried out clinical studies
regarding the protective role of flavonoids in cardiovascular diseases. The cardioprotective effects have been thought to stem from their free radicals scavenging,
anti-oxidant, anti-thrombotic, anti-apoptotic and anti-hypertensive effect.
2.
Antimicrobial activies of flavonoids was carried out by T.P.Tim Cushnie,
Andrew J. Lamb2, where they found out that this class of natural product is
becoming the subject of anti-infective research, reports of activity in the field of
anti-bacterial flavonoid was widely conflicting, probably owing to inter and intra
assay variation in susceptibility testing. They have worked on flavonoids whose
mechanism of action has been investigated include robinetin, myricetin, apigenin,
rutin,galangin 2,4,2’-trihydroxy 5’-methylchalcone and lonchocarpol, regarding
antimicrobial activity.
Galangin
3.
Rutin
Investigation in the binding and anti-oxidant properties of the plant
flavonoid Fisetin in model bio-membranes was done by Bidisha Sengupta, Anvesha
Bannerjee and Pradeep K. Sengupta5. Where they demonstrated the nobel use of
intrinsic flurosence characteristics of plant flavonoid Fisetin. (3,3’,4’,7-OH
Flavone) to explore its binding and site(s) of solubilisation in egg lecithin
7
liposomal membranes.
OH
HO
OH
OH
O
4.
Hypolipidimic
and
Fisetin
anti-oxidant
effects
of
total
flavonoids
of
PerillaFrutescens leaves in hyperlipidemia rats induced by high-fat-diet was
studied by Li-Jun Feng, Chen-Huan Yu, Ke-Jing Ying, JianHua, Ziao-Yan Dai6
where they found out that total flavonoids of PerillaFrutescens leaves(TFP),
consisted of apigenin with a small amount of luteolin which was highly effective in
decreasing the level of serum total cholesterol(TC) triaglycerols(TG), low density
lipoprotein cholesterol and adipose tissue lipid accumulation.
OH
HO
OH
5.
JulienBoccard,
O
FainaBajot,
Apigenin
Attilio
Di
Pietro,
Serge
Rudaz,
AhceneBoumendjel, Edwige Nicolle, Pierre-Alain Carrupt.7 carried out A3D linear
solvation energy model to quantify the affinity of flavonoid derivatives toward Pglycoprotein and reported flavonoids as potent Pgp inhibitors are able to bind to the
systolic ATP binding site and vicinal hydrophobic pocket. The 3D QSAR was used
to analyze a set of flavonoid derivatives.
6.
S. Suzgec-selcuk, A.S.Birteksoz3 worked on anti-oxidant and anti-
microbial activities form the flavonoids of Helichrysunchasmolycicum. They
obtained ethanol extract of the arial parts of H. chasmolycicum which showed antimicrobial properties of DPPH method (IC50 0.92 mg/ml). Anti-microbial tests were
performed on the several extracts and also 3,5-dihydroxy-6,7,8-trimethoxy flavone
8
and kaempferol 3-o-glucoside obtained from the aerial parts of the same.
O
CH3
O
O
CH3
O
O
OH
7.
O
CH3
3,5-dihydroxy-6,7,8-trimethoxy flavone
W.Bylka, I.Matlawska, N.A.Pilewski4 worked on natural flavonoids used as
anti-microbial agents and their present report is a review of flavonoids that have a
proven inhibitory activity against a variety of human pathogens including antibiotic
resistant gram positive, gram negative bacteria and viruses.
8.
Ali El Antri, NadyaLachkar, Hanane El Hajjaji, Farah Gaamoussi,
BadiaaLyoussi, Brahim El Bali et al
8
worked on Structural elucidation and
vasodilator activity of methoxyflavonols from Calycotomevillosasubsp. Intermedia.
Two flavonols identified as 3, 5, 7, 4’-tetrahydroxy-3’-methoxyflavone and 3, 5, 7,
4’-tetrahydroxy-8-methoxyflavone
were
isolated
form
the
seed
of
Calycotomecillosa subsp. Intermedia. Vasodilator activity of compound was
demonstrated in isolated rat aorta contracted with high KCl with noradrenaline.
OH
HO
O
OH
9.
O
CH3
3,5,7,4’-tetrahydroxy-3’-methoxyflavone
Niina M.M. Sriratna, Laura Veeroos, Lars J. Granlund, Viivi H. Hassinen,
Kai Kaarniranta, Reijo O. Karjalainen9 worked on Plant flavonolquercetin and
isoflavonebiochanin A differentially induce protection against oxidative stress and
inflammation in ARPE -19-cells and found out that quercetin reduce the expression
of cytokins IL6 and IL1β. In the cells treated with hydrogenperoxide
and
expression levels of Nrf2 and ho-1 were increased by quercetin treatment
suggesting protective function against oxidative stress.
9
10.
Biswanath Das, PonnaboinaThirupathi, BommenaRavikanth, RathodArvind
Kumar, AkellaVenkataSubramanayaSarma, and ShaikJilani Basha10 worked on
isolation,
synthesis
and
bioactivity
of
homoisoflavonoids
from
Caesalpiniapulcherrima. The anti-bacterial and anti-fungal activities of the isolated
homoisoflavonoids were studied.
11.
Marta Correia-da-Silva, Emilia Sousa, Barbara Duarte, Franklim Marques,
Felix Carvalho, Luis M. Cunha-Ribeiro and Madalena M.M. Pinto11 worked on
flavonoids with an oligopolysulfated moiety. In their overall results, the
polysulflavonosides showed the potential as a new infective and safe agents for
anti-coagulant therapy.
H3C OR O
OR
OH
OR
O
O
CH3
O
O
OR
O
OR
OR
OH
O
New anti-coagulant small molecules.
R=SO 3
12.
Zava DT, Duwe .G12 worked on Estrogenic and anti-proliferative properties
of genistein and other flavonoids in human breast cancer cell\invitro. Their results
reveal that Genistein is unique among the flavonoid tested. In that it has potent
estrogen agonist and cell growth-inhibitory actions over a physiologically relevant
concentration range.
HO
OH
O
OH
13.
Genistein
Hitoshi Kagawa13 Tetsuya Takahashi, Mariko Uno, Shigeru Ohta and
Yoshihiro Harigaya worked on the synthesis of Deuterium-labelled flavanones
which was achieved by the treatment of flavanones and 2’-hydroxychalcones with
D3PO4 and AcOD.
14.
Zhiyan Huang, Fang Fang, Junijan Wang, Chi-Wai Wong14 worked on the
10
structural activity relationship of flavonoids with estrogen-related receptor gamma
and investigated the SAR of flavonoids with estrogenrelated receptor γ and
it’scoactivator peroxisome proliferators-activated receptor γ co-activator-1alpha.
These placones and flanonols utilize alternative mechanisms to influence the
transcriptional activities of EER γ and PGC-1alpha.
15.
Hideyu Goto, YoshiyasuTerao, and Shuji Akai15 carried out the synthesis of
various kinds of isoflavones, isoflavanes, and biphenyl-ketones and their 1,1Diphenyl-1,2-picrylhydrazyl and their radical scavenging activities. Forty eight
kinds of isoflavones, thirty-one isoflavones, and forty seven biphenyl-ketones
wesized from eleven kinds of substituted phenols and six phenylacetic acids.
Among them, seventy-five compounds are new. The radical scavenging
activitivities
of these compounds
were evaluated using 1,1-diphenyl-2-
picrylhydrazyl (DPPH) at pH 6.0.
O
+
N
O
H3C
.
N
-
+
O N
CH2
16.
+
N
O
O
-
1,1-Diphenyl-1,2-picrylhydrazyl
Madalein Blanc et al16 worked on 2’-Amino-alpha-chloroacetophenone as a
valuable tool for the synthesis of conviniently-substituted alpha, betaepoxychalcone derivatives they carried out Darzens condensation of 2’-amino3’,5’-dimethoxy-alpha-chloroacetophenone
with
benzaldehydes
undergoing
different cyclization possibili ties and afford a variety of flavonoids analogs with
biological potential.
17.
Julio A.Seijas et al17 carried out Studies on the synthesis of flavonoids by a
two component reaction using microwave heating, flavonoids in this field were
realised to lack data for the 2 component reaction of acetophenones and
benzaldehydes, although synthesis of chalcones by reaction of these components
were reported, all of the acetophenones studied lack 2-OH-substitutent that could
allow the subsequent cyclization to close pyrane ring present in flavanones.
11
18.
Armandodoraino Bianco et al18 carried out a new Synthesis of Flavonoids
via Heck reaction, several naturally ocurring Flavonoids was proposed based on use
of Heck reaction. The key step involves the coupling of an aryl vinyl ketone with an
aryl iodide.
OR`
OR
HO
O
chalcones
19.
Bastien Nay et al
19
R=H, Me
R=H, Ac
, worked on Methods in Synthesis of Flavonoids. Part
3: Molybdenum(IV)-catalyzed coupling of Cinnamyl Alcohols to Phenol derivatives
the paper deals with the formal total synthesis of Flavonoids bearing the
Hydroxylation pattern of the catechin series based on an access to the fully
functionlised skeleton via the alkylation of phloroglucinol tribenzyl ether by 3,4dibenzyl oxycinnamyl alcohol. This reaction was reavealed to be most successful
when catalysed by the Mo(acac)2(SbFe)2 complex. In addition the underlying
concepts to the different ways that can be used in this C8-C3+C8 strategy are
discussed.
20.
Synthesis, growth inhibition and cell cycle evaluation of novel flavonoid
derivatives was done by Yerra Koteswara Rao, Shih-Hua Fang and Yew-Min
Tzeng20. They synthesized the series of 10 flavonoid derivatives by cyclization of
substituted calcones and evaluated their biological activity. Certain derivatives
showed significant growth inhibitory action against a panel of tumor cell lines
including Jurkt, PC-3 and colon 205.
21.
Soman SS21 et al synthesized new furoflavonones from hydroxyl acetyl
benzofuran and an aryl aldehyde in presence of piperidine. They concluded that the
chalcone synthesized using 1% ethanolic sodium hydroxide from hydroxyl acetyl
benzofuran and aryl aldehyde shows anti-inflammatory activity.
12
R
-
O
O
O
Ar
Ar=-C 6H5 2
p-C 6H4(OCH 3) 3
p-C 6H4(Cl) 4
furoflavonone
22. Von-Konstanecki method for the synthesis of flavones using claisen condensation
in which o-methoxybenzoate reacts with acetophenone in presence of sodium. The
conclusive step includes elimination of water molecule to form flavones.22
O
OCH 3 OCH 3
O
Ph
Na
O

OCH 3
o-methoxybenzoate
O
1,3-diketone
OH
O
H2O
Ph
OCH 3
O
intermediate
Flavone
13
HI
6.4 Objectives of the study
1. To synthesize some newer derivatives of flavonoids.
2. To characterize the synthesized compounds by different analytical techniques
such as IR, NMR and Mass spectral data.
3. To screen the synthesized compounds there in vivo anti inflammatory and in vitro
antioxidant activity.
4. To publish the research works in peer reviewed journals.
ACTIVITIES
Literature survey
Synthesis and collection of analytical
data
Pharmacological activities
Typing of thesis book and sending for
publication
Total
14
DURATION
Till the completion of project
6 Months
3 Months
1 Month
10 Months
7.0
Materials and methods:
7.1 Sources of data
Databases like Chemical abstracts, Biological abstracts, Medline, and Journal of
Chemistry section B, Indian Journal of Heterocyclic Chemistry, European Journal of
Medicinal Chemistry, Bioorganic and Medicinal Chemistry Letters, Actacrystallographica,
throughHelinet of RUGHS etc.
7.2 Method of collection of Data
A) Synthesis of the compounds:
Chemicals and other reagents required for the synthesis will be procured from
standard company sources. Compounds will be synthesized by using standard
procedures. The reactions will be monitored by TLC and purification of the compounds
will be carried out by recrystallization method using suitable solvent.
Scheme:O
O
1
R CHO
R
R
Flavonoids
NaOH
CH3
R
chalcone
1
-
Ar
H3C
1
R=
R =
H
O
R1= Different aldehydes
O
O
H
4-chlorobenzaldehyde
O
OH
Cl
H
H
4-hydroxybenzaldehyde
anthracene-9-carbaldehyde
O
O
NO 2
H
H
O
4-nitrobenzaldehyde
naphthalene-1-carbaldehyde
O
O
H
furan-2-carbaldehyde
15
B) Characterization of the compounds:
The synthesized compounds will be characterized by preliminary laboratory techniques
such as melting point, boiling point etc and by FTIR, Mass Spectroscopy and NMR
spectral data
C) 1))Screening of anti-oxidant activity: 27
In vitro anti-oxidant activity study:
DETERMINATION OF 1,1-DIPHENYL-2-PICRYYLHYDRAZYL(DPPH)
RADICAL SCAVENGING ACTIVITY
Procedure:
 The scavenging activity for DPPH free radical will be measured according to the
procedure described by Braca et al., 2001. An aliquot of 3 ml of 0.004% DPPH
solution in ethanol and 0.1 ml of test sample at various concentrations will be
mixed. The mixture will be shaken vigorously and allowed to reach steady state at
room temperature for 30 min. Decolorisation of DPPH will be determined by
measuring the absorbance at 517 nm. A control will be prepared using 0.1 ml of
respective vehicle in the place of test sample.
Calculation of percentage inhibition:
The percentage inhibition of radical by the test sample will be calculated using the
formula:
INHIBITORY RATIO = (Ao-A1)x100/Ao
Where
A0 is the absorbance of control;
A1 is the absorbance with addition of test sample.
2) Screening of anti-inflammatory activity:22-25
In vivo anti-inflammatory activity study:
Method Used: Carrageenan-induced paw edema model.
16
Animals Used: Albino Wistar rats.
Number of animals used: 72 numbers
Carrageenan-induced paw edema model:
A 1% w/v suspension of carrageenan will be prepared freshly in normal saline and
injected into sub plantar region of left hind paw (usually 0.1 mL in rats and 0.025-0.05
mL in mice). In control group animals, only vehicle will be injected. Test drug is
usually administered orally or intraperitoneally, according to body weight immediately
or half an hour or one hour before (depending on the expected peak effect) carrageenan
challenge. A mark will be made on the ankle joint of each rodent. Paw volume up to
the ankle joint will be measured in drug treated and untreated groups before and after 3
h of carrageenan challenge using a plethysmograph filled with mercury.
7.3 Does the study require any investigation or interventions to be conducted on
patients or other humans or animals?
YES
8.0
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
OBTAINED & ENCLOSED
Reference:
1. Nandave M, S KOjha and D S Arya. Protective role of Flavonoids in
Cardiovascular diseases; NPR; 2005 May-Jun: 4(3):166-75.
2. Tim Cushnie T P and Lamb J A. Anti-microbial activities of Flavonoids. Int J.\
Anti-microb Agents 2005.343-56.
3. S. Suzgec-selcuk, A.S.Birteksoz. Flavonoids of Helichrysunchasmolycicum and its
anti-oxidant and anti-microbial activities. South African J. Bot.;2010 April; 170-74
4. W.Bylka, I Matlawska and N A Pilewski. Natural Flavonoids as anti-microbial
17
Agents. JANA; 7(2):24-30.
5. Sengupta B, Bannerjee A and Sengupta P K. Investigation on the Binding and antioxidant properties of Flavonoids Fisetin in model biomembranes. Hypolipidemic
and anti-oxidant effects of total flavonoids of Perilla Frutescens leaves in
hyperlipidemia rats induced by high-fat-diet. FEBS Lett. 2004 Jul. 16.; 570(1): 7781.
6. L. Feng, C. Yu, K. Ying, J. Hua, X. Dai. Food Res. Int. 2010 Aug.; 404-409.
7. Julien B., Faina B., Attilio D.P., Serge R. , Ahcene B., Edwige N., P. Carrupt. A 3D
linear solvation energy model to quantify the affinity of flavonoid derivatives
toward P-glycoprotein. Eur J Pharm Sci 2009 Feb 15; 36(2-3): 254-64.
8. El Antri A, Lachkar N, El Hajjaji H, Gaamoussi F, Badiaa Lyoussi, Brahim et al.
Structure elucidation and vasodilator activity of methoxyflavonols from
Calycotomevillosasubsp. Intermedia. Arab J Chem 2003 March. 173-178.
9. Niina M.M. Sriratna, Laura Veeroos, Lars J. Granlund, Viivi H. Hassinen, Kai
Kaarniranta and Reijo O. Karjalainen. Plant flavonol quercetin and isoflavone
biochanin: a differentially induce protection against oxidative stress and
inflammation in ARPE -19-cells. Food Res Int 2010 Oct.; 44(1): 109-13.
10. Biswanath D, Ponnaboina T, Bommena R., Rathod A.K., Akella Venkata S.S., and
Shaik J.B. Isolation, synthesis and Bioactivity of Homoisoflavonoids from
Caesalpiniapulcherrima. Chem Pharm Bull 57(10): 1139-41.
11. Correia-da-Silva M, Sousa E, Duarte B, Marques F, Carvalho F and Cunha-Ribeiro
M.L. Flavonoids with an Oligopolysulfated Moiety: A New Class of Anticoagulant Agents. J Med Chem 2010 Jun.; 95-106.
12. Zava D T and Duwe G. Estrogenic and anti-proliferative properties of genistein and
other flavonoids in human breast cancer cell in vitro. Nutr Cancer 1997;27(1):31-40
13. Hitoshi K., Tetsuya T., Mariko U., Shigeru O. and Yoshihiro H. Synthesis of
Deuterium-labelled flavonones. Cambulpharm 2004 Jun; 953-956.
14. Z Huang, F. Fang, J. Wang, C.Wong. Structural activity relationship of flavonoids
with estrogen-related receptor gamma. FEBS Lett 2009 Nov.;584(1);22-26
15. Goto H, Terao Y and Akai S. Synthesis of various kinds of Isoflavones,
Isoflavanes, and Biphenyl-Ketones and their 1,1-diphenyl-2-picrylhydrazyl
18
Radical-Scavenging activities. Chem Pharma Bull 2009 Apr; 57(4):346-360.
16. Madalein B., Maud M., Sabrina O. and Ahcene B. 2’-Amino-alphachloroacetophenone as a valuable tool for the synthesis of conviniently-substituted
alpha, beta- epoxechalcone derivatives. Chem Pharma Bull 2005 Apr.;53(4):435436.
17. Julio A.Seijas, M.Pilar Vazquez-Tato and Raquel Carballido-Reboredo. Studies on
the synthesis of flavonoids by a two component reaction using microwave heating.
ECSOC 2002 Sept.6 (1-30).
18. Armandodoraino B, Claudia C, Angela F, Marcella G and Carolina M A new
synthesis of flavonoids via Heck reaction. Tetrahedron Lett.2003 15 Dec; 44(51)
:9107-109.
19. Bastien N., Magalie C., Marjolene L., Catherine C. and Joseph V. Methods in
synthesis of flavonoids. Part 3: molybdenum (IV)-catalyzed coupling of cinnamyl
alcohols to phenol derivatives. Tetrahedron Lett 2002 Apr; 43(15): 2675-678
20. Yerra K. R., Fang S and Tzeng Y. Synthesis, growth inhibition and cell cycle
evaluation of novel flavonoid derivatives. Bio-org med chem 2005 Sept; 13(24):
6850-855.
21. Soman S.S. and Patel M .J. One-pot synthesis of furoflavonones. Ind J Hetero
Chem 2010 Jan.-Mar;19: 209-14.
22. Ahmad F., Idris H S M and Adib M A. Synthesis and characterization some
flavonoid derivatives.Universiti Technologi Malaysia 2006.1-22.
23. Kulkarni SK. Hand Book of Experimental Pharmacology. 2nd ed. Vallabh
Prakashan. 1999, p. 123-8.
24. Winter CA, Risley EA, Nuss GN. Carrageenan induced edema in hind paw of the
rats as an assay for anti-inflammatory drugs. Proc soc Exp Biol 1962; 86(111): p.
544-7.
25. Raman K, Parmar SS, Salzman SK. Anti-inflammatory activity of substituted 1,3,4oxadiazoles. J Pharm Sci 1989;78:999-1002
26. www.seacoast.com/topic. ghp
27. Braca A, Sortino C, Politi M, Morelli I and Mendez J. Antioxidant activity of
flavonoids from Licania licaniaeflora. J Ethnopharmacol 2002 Mar; 79(3): 379-81.
19
9.0
Signature of the Candidate
10.0
Remarks of the Guide
11.0
Name and Designation of
11.1Guide
Mr. Gurubasavaraja Swamy
Asst.Professor,
Department of Pharmaceutical Chemistry,
Acharya& B.M. Reddy College of Pharmacy,
Soldevanahalli,
Bangalore-90
11.2 Signature
11.3 Co-Guide
NIL
11.4 Signature
11.5
Head
Department
of
the Dr. Amit Kumar Das
Professor,
Department of Pharmaceutical Chemistry,
Acharya & B.M. Reddy College of Pharmacy,
Soldevanahalli,
Bangalore-90
11.6 Signature
12.0
12.1 Remarks of Principal
12.2 Name of the Principal
Dr. Divakar Goli
Principal,
Acharya & B.M. Reddy College of Pharmacy,
Soldevanahalli,
Bangalore-90
12.3 Signature
20