Microwave assisted synthesis, physico-chemical properties and antioxidant activity of α,β-unsaturated benzimidazole derivatives incorporated with baritone moiety

Article abstract of DOI:10.14233/ajchem.2013.13187

A series of (2E)-1-(H-benzimidazol-2-yl)-3-substituted phenyl 2-propen-1-one linked with barbitone (5a-g) are synthesized by both conventional method and microwave assisted method. The benzimidazole chalcones (4a-g) were prepared from the condensation of 2-acetyl benzimidazole (3a) with different aromatic aldehydes. These chalcones on reaction with barbituric acid in presence of acetic acid medium gave the a,b-unsaturated benzimidazole derivatives. The structures of the all the final compounds were established on the basis of IR, 1H NMR, mass spectra and elemental analysis. The druglikeness and physicochemical properties of the derivatives were determined by actelion, molsoft, molinspiration and ACD ChemDraw Ultra 11.0 software. The final products possess a favourable drug likeness and drug score. All the final synthesized compounds were screened for their antioxidant properties like free radical scavenging by DPPH method. Among the synthesized compounds (5f), (5c) and (5d) were exhibited a good antioxidant activity and all the other derivatives showed a moderate activity.

Full text of DOI:10.14233/ajchem.2013.13187

Asian Journal of Chemistry; Vol. 25, No. 4 (2013), 1853-1856
http://dx.doi.org/10.14233/ajchem.2013.13187
Microwave Assisted Synthesis, Physico-chemical Properties and Antioxidant Activity of
α,β-Unsaturated Benzimidazole Derivatives Incorporated with Baritone Moiety
1,*
2
3
BIJO MATHEW , A. JERAD SURESH and S. ANBAZHAGAN
1Department of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad-678 004, India
2Department of Pharmaceutical Chemistry, Madras Medical College, Chennai-600 003, India
3Department of Pharmaceutical Chemistry, Karuna College of Pharmacy, Palakkad-679 533, India
*Corresponding author: Fax: +91 491 2508537; E-mail: bijovilaventgu@gmail.com
(Received: 6 December 2011;
Accepted: 5 October 2012)
AJC-12234
A series of (2E)-1-(H-benzimidazol-2-yl)-3-substituted phenyl 2-propen-1-one linked with barbitone (5a-g) are synthesized by both
conventional method and microwave assisted method. The benzimidazole chalcones (4a-g) were prepared from the condensation of
2-acetyl benzimidazole (3a) with different aromatic aldehydes. These chalcones on reaction with barbituric acid in presence of acetic acid
medium gave the α,β-unsaturated benzimidazole derivatives. The structures of the all the final compounds were established on the basis
of IR, 1H NMR, mass spectra and elemental analysis. The druglikeness and physicochemical properties of the derivatives were determined
by actelion, molsoft, molinspiration and ACD ChemDraw Ultra 11.0 software. The final products possess a favourable drug likeness and
drug score. All the final synthesized compounds were screened for their antioxidant properties like free radical scavenging by DPPH
method. Among the synthesized compounds (5f), (5c) and (5d) were exhibited a good antioxidant activity and all the other derivatives
showed a moderate activity.
Key Words: 2-Acetyl benzimidazole, Barbituric acid, Chalcones, Antioxidant activity.
derivatives has yet been undertaken. The two pharmacophores
are linked by means of carbon-carbon double bond. Some
experimental protocols have been made for this purpose and
excellent results have been obtained. The synthesis of 5-[(2E)-
1-(1H-benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-
ylidene]pyzrimidine-2,4,6-(1H, 3H, 5H)-trione (5a-g) described
in this study are outlined in Scheme-I. Ortho-phenyelenediamine
reacts with lactic acid gave 2(α-hydroxyethyl)benzimidazole
(2a), which on subjected with oxidation in presence of potassium
dichromate produced 2- acetyl benzimidazole (3a). The
chalcones (4a-g) were prepared by reacting 2-acetyl benzimi-
dazole with appropriate aldehydes in the presence of a base
by Claisen-Schmidt condensation24. The condensation of
benzimidazole chalcones (4a-g) with barbituric acid in acetic
acid gave (5a-g)25,26. The acidic hydrogen present in the pyrimi-
dine nucleus of barbituric acid undergoes interamolecular acid
catalyzed dehydration resulting an activated C=C bond in the
final derivatives. The structures of the all the final compounds
were established on the basis of spectral analysis.
INTRODUCTION
Free radicals are chemical species possessing an unpaired
electron that can be considered as fragments of molecules and
which are generally very reactive. There is an increasing
evidence of the implication of free radicals and reactive oxygen
species in a variety of diseases and pathophysiological events
including cancer, inflammations and myocardial infraction1,2.
Benzimidazoles are regarded as a promising class of biologically
active agents. The benzimidazole nucleus exhibit a wide range
of biological profile such as, antimicrobial3-6, antitubercular7,8,
anticancer9-13, angiotensin II receptor antagonists14. The benzi-
midazole also known to exhibit significant activity against
several viruses such as human cytomegalovirus, HIV15,
herpes16, RNA17 and influenza18.
Barbituric acid is hydroxy pyrimidine nucleus extensively
used in the class of hypnotics19-22. The nucleus has highly reactive
acidic hydrogen atoms on the carbon atom α to both carbonyl
groups. The ability of these hydrogen atoms to react with a
carbonyl compound is already reported23. Inspired from these
findings, our research was focused on the connection between
α, β unsaturated ketone of benzimidazole derivatives with
barbituric acid. To our best of knowledge, no screening of the
free radical scavenging effect of the synthesized barbitone
EXPERIMENTAL
Melting points were determined by using melting point
apparatus MP-DS TID 2000V and the values were uncorrected.
Reactions were monitored by thin layer chromatography (TLC)

1854 Mathew et al.
Asian J. Chem.
on pre coated silica gel G plates using iodine vapour as visuali-
zing agent. IR spectra were recorded on JASCO FT/IR-140
spectrophotometer by using KBr pellets technique. PMR spectra
were recorded using BRUCKER FT-NMR-500 MHz spectro-
photometer by using DMSO as solvent and TMS as internal
standard. The chemical shift was expressed in δ ppm. Mass
spectra were recorded on a JEOL GCmate mass spectrometer.
high calculated log P and low TPSA. Polar surface area being
an indication of compound's capacity to form hydrogen bonds.
It is noted that the incorporation of a barbitone moiety in the
benzimidazole chalcone gave favourble positive druglikeness
score determined by bothActelion and Molsoft. Druglikeness
is a measure of similarity of a proposed drug compound to
general population of drugs in use29. The predicted log BB
decreases in the final derivatives due to the more polar group
participation. The presence of NO2 in the aromatic nucleus
increases the TPSA and decreases the predicted log. The
physico-chemical properties of the newly synthesized
candidates were shown in Table-1.
OH
N
OH
NH
NH
2
H C
3
+
N
H
CH
3
COOH
2
2a
Synthesis of 2-(α-hydroxyethyl) benzimidazole (2a):
Ortho-phenylenediamine (0.25 mol) was mixed with lactic acid
(0.35 mol) in a round bottom flask and refluxed for 3 h. The
reaction mixture was cooled added with 10 % NaOH until
bacisity to litmus paper. The crude pink colured product
obtained was thoroughly washed with water and dissolved in
400 mL of boiling water. To this add 2 g of decolourising
carbon was added and heated for 15 min. The mixture was
filtered rapidly at the pump through a preheated buchner
funnel. The product obtained was further filtered and washed
with (25 X3) mL cold water and dried at 100 ºC. The yield
was found to be 78 %.
K Cr O
H SO
2
2
7
2
4
O
R
N
O
N
R -CHO
10%KOH
N
H
N
H
CH
3
4a-f
O
3a
HN
NH
CH COOH
3
O
O
R
H
N
O
O
5a: phenyl
5b: 4- chloro phenyl
5c: 4- methoxy phenyl
5d: 4-dimethyl phenyl
5e: 3- nitro phenyl
Synthesis of 2-acetyl benzimidazole (3a): To a solution
of 2-(α-hydroxy) ethyl benzimidazole 2a (0.01 mol) in dil.
H2SO4 (5 %, 40 mL) was drop wise added the solution of
K2Cr2O7 (0.15 mol) and H2SO4 (25 %, 80 mL) with constant
stirring at room temperature over a period of 20 min. Further
the reaction mixture was stirred at room temperature for 2 h.
After completion of the reaction (monitored by TLC), the
reaction mixture was neutralized with aqueous NH3 solution
(1:1) and resultant orange solid was filtered, washed with water
and dried, recrystallized from ethyl acetate.
NH
N
O
5f: 2-hydroxy phenyl
N
H
R
Scheme-I: Synthetic route of the titled compounds
In silico screening: In silico screening is an effective
tool for the determination of the druglikeness of a molecule.
Parameters related to druglikeness of the derivatives were
established on the basis of Lipinski's Rule of 527. The drug
likeness and physicochemical properties of the derivatives were
determined by actelion, molsoft and molinspiration and ACD
ChemDraw Ultra 11.0 software. Blood-brain barrier prediction
of the set of compounds was calculated by DEC-1 model28.
The results were indicated in Table-1. It has been noted that
the better brain penetration is predicted for compounds have
General Synthesis of (2E)-1-(1H-benzimidazol-2-yl)-
3-phenylprop-2-en-1-one (4a-h): 2-Acetyl benzimidazole
(0.01 mol) and appropriately substituted aromatic aldehydes
(0.012 mol) were mixed in ethanol (20 mL) containing 10 %
aq. KOH (8 mL) and magnetically stirred the solution cons-
tantly at room temperature for 10 h. The whole mixture was
transferred in to 100 mL ice cold water and acidified with dil.
TABLE-1
PHYSICOCHEMICAL PROPERTIES OF THE SYNTHESIZED DERIVATIVES
Drug likeness
Compound
ACD logPa
C logPb
mi logPc
TPSAd
log BBe
Molsoft
Actelion
-2.47
1.82
4a
4b
4c
4d
4e
4f
3.27
4.05
3.32
3.88
2.85
3.01
3.82
3.41
4.08
3.46
3.51
3.34
3.21
3.04
3.65
2.93
3.03
3.04
2.74
3.61
1.88
2.49
1.77
1.88
1.89
1.58
3.40
4.08
3.46
3.51
3.34
3.16
3.92
2.31
2.99
2.36
2.41
2.24
2.07
45.75
45.75
54.98
-0.07
0.017
-0.11
-0.12
-0.15
-0.42
0.01
0.39
0.63
0.29
-0.49
-0.86
0.06
-0.38
1.02
1.15
0.63
0.79
0.01
0.47
1.09
48.99
91.57
-3.19
0.07
0.99
65.98
45.75
4g
5a
5b
5c
5d
5e
5f
-4.07
0.82
0.60
111.47
111.48
120.71
114.71
157.302
131.71
-1.22
-1.13
-1.37
-1.27
-1.90
-1.57
0.81
0.20
0.22
0.84
aCalculated by ACD ChemDraw Ultra 11.0 software; bCalculated by Actelion; c & d Calculated by Molinspiration; eCalculated by DEC-I model [log
BB = -0.0148 (miTPSA) + 0.152 (C log P) + 0.139]

Vol. 25, No. 4 (2013)
Microwave Assisted Synthesis of α,β-Unsaturated Benzimidazole Derivatives 1855
HCl. The solid formed was washed, filtered and dried, recrys-
tallized from ethanol yield a product of (4a-f).
(KBr) 3379 (Ar-OH), 3231 (NH str). 1680 (C=O), 1562 (C=N)
1H NMR (DMSO d6 + CDCl3) in δ ppm: 9.1 (1H, s, NH benzi-
midazole), 8.4-8.8 (2H, s, pyrimidine NH), 6.4-8.5 (10H, m,
8ArH, 2 CH=CH), 5.62 (1H, s, ArOH) MS: 375.64 (M+1).
Calcd./Anal. (%) [C 61.17/61.25, H 3.77/3.79, N 14.97/14.86].
Antioxidant activity by DPPH method: The scavenging
activity of the synthesized candidates (5a-f) on DPPH radical
was determined according to the methods of Shimada et al.30.
Different concentration of the test compounds in 1.5 mL of
methanol were added to a 1.5 mL (0.2 mM) solution of DPPH
radical in methanol. The above solutions were allowed to react
at room temperature for 0.5 h.After 0.5 h the absorbance values
were measured at 517 nm and converted to percentage of scaven-
ging activity, which was calculated by using the following
formula. The IC50 and percentage inhibition of the newly
synthesized candidates were compared with standard ascorbic
acid and the values were shown in Table-2.
Synthesis of (5a-f): To a solution of (4a-g) (0.01 mol)
suspended in 7 mL acetic acid, barbituric acid (0.01 mol) was
added with constant stirring. The reaction mixture was then
refluxed for 7 h with occasional stirring. The resultant contents
were poured in to in to crushed ice. The crude product was
filtered and recrystallized from methanol.
Microwave assisted synthesis: Barbituric acid (0.01 mol)
was added to a mixture of chalcone (4a-g) (0.01 mol) in acetic
acid. The reaction mixture was irradiated for 2-3 min at 60 %
microwave power with 30 sec interval using a domestic
microwave oven. The reaction progress was monitored by TLC.
The resultant contents were poured in to in to crushed ice with
constant stirring. The isolated product was recrystallized from
methanol.
5-[(2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-
1-ylidene]pyrimidine-2,4,6-(1H, 3H, 5H)-trione (5a): Brown
solid, yield 77 %, m.p. 255-258 ºC; IR(KBr) :3230 (NHstr),
1693 (C=O), 1587 (C=N), 1H NMR (DMSO d6 + CDCl3) in δ
ppm: 9.1 (1H, s, NH benzimidazole) 8.0-8.4 (2H, s, pyrimidine
NH) 6.48.1 (11H, m, 9 ArH, 2CH=CH). MS: m/z = 359.21
(M++1). Calcd/Anal. (%) [C67.03/67.12, H3.94/3.81, N15.63/
15.59].
(Ab + As) − Am


×100
Percentage of scavenging activity =


Ab


where, [Ab: absorbance of 1.5 mL DPPH + 1.5 mL methanol,
Am: Absorbance of 1.5 mL DPPH + 1.5 mL drug solution,
As: Absorbance of 1.5 drug + 1.5 mL methanol solution].
RESULTS AND DISCUSSION
5[(2E)-1-(1H-benzimidazol-2-yl)-3-(4 chlorophenyl)-
prop-2-en-1-ylidene]pyrimidine2,4,6(1H,3H,5H)-trione
(5b): Yellow solid, yield 77 %, m.p. 265-267 ºC; IR (KBr):
3238 (NHstr), 1696 (C=O), 1584 (C=N), 1H NMR (DMSO d6
+ CDCl3) in δ ppm: 8.9 (1H, s, NH benzimidazole) 8.4-8.6
(2H, s, pyrimidine NH), 6.4-8.3 (10 H, m, 8ArH, 2CH=CH).
MS: m/z = 394.1 (M+1). Calcd/Anal. (%) [C 61.16/61.23, H
3.34/3.32, N 14.26/14.28].
The highly reactive acidic hydrogen present in the barbituric
acid has a tendency to react with ketone group in the, α,β-
unsaturated carbonyl system in presence of an acetic acid
medium. The structures of the final products were confirmed on
the basis of spectral studies.All the newly synthesized compounds
were characterized by IR, 1H NMR and mass spectroscopic
data. IR spectrum of the 5-[(2E)-1-(1H-benzimidazol-2-yl)-
3-(4-chlorophenyl)prop-2-en-1-ylidene]pyrimidine-2,4,6-
(1H,3H,5H)-trione (5b) showed a strong absorption band at
3238 cm-1 corresponding to benzimidazole NH. The absorption
at 2910 and 2878 cm-1 corresponds to pyrimidine NH/NH. A
sharp absorption at 1696 cm-1 corresponds to carbonyl stretching
and 1232 cm-1 due to aryl chloride. The 1H NMR spectra showed
the singlet peak at δ 8.4 and 8.6 were assigned to pyrimidine
NH/NH. The singlet peak at δ 9.1 corresponding to benzimi-
dazole NH. The doublet for vicinal protons along with the
aromatic multiplet between δ 6.4-8.2 ppm. Mass spectrum of
compound 5b revealed the molecular ion peak [M+2] at m/z
394 corresponding to the molecular mass of the compound.
Free radical scavenging properties of the synthesized
derivatives were evaluated by decrease in the absorption of
the stable DPPH radical at 517 nm. This bleaching of DPPH
absorption occurs when the odd electron of the radical is
paired30.All the newly synthesized barbitone derivatives incor-
porated with a α,β unsaturated benzimidazole derivatives were
showed a good DPPH free radical scavenging activity. In this
study we proposed that decrease in the DPPH absorption due
to the two NH group in the pyrimidine moiety, which can donate
hydrogen atom and exist in radical form and the electron
conjugation effect in the structure stabilizes the radical so that
it does not involved in a destructive biochemical reaction. The
highest activity is shown in the participation of electron
donating group in the aromatic nucleus of the final products.
5-[(2E)-1-(1H-benzimidazol-2-yl)-3-(4-methoxy-
phenyl)prop-2-en-1-ylidene]pyrimidine-2,4,6-(1H,3H,5H)-
trione (5c): Pale green solid, yield 67 %, m.p. 225-2228ºC;
IR (KBr): 3239 (N-H str), 1681 (C=O), 1576 (C=N), 1H NMR
(DMSO d6 + CDCl3) in δ ppm: 8.9 (1H, s, NH benzimidazole)
8.4-8.6 (2H, s, pyrimidine NH), 6.4-8.3 (10H, m, 8 ArH,
2CH=CH). 3.3 (3H, s, OCH3) MS: m/z = 390.12 (M+1). Calcd./
Anal. (%) [C61.16/61.23, H 3.34/3.32, N 14.26/14.28].
5-{(2E)-1-(1H benzimidazol-2-yl)-3-[4(dimethylamino)-
phenyl]prop-2-en-1-ylidene}pyrimidine-2,4,6-(1H,3H,5H)-
trione (5d): Brown solid, yield 76 %, m.p.-210-213 ºC; IR
1
(KBr) 3227 (N-H str). 1678 (C=O), 1569 (C=N), H NMR
(DMSO d6 + CDCl3) in δ ppm: 8.9 (1H, s, NH benzimidazole),
8.5-8.7 (2H, s, pyrimidine NH), 6.3-8.4 (10 H, m, 8Ar H,
2CH=CH). 3.3 (6H, s, N(CH3)2. MS: 402.56 (M+1). Calcd./
Anal. (%) [C 65.83/65.91, H 4.77/4.72, N 17.45/17.53].
5-[(2E)-1-(1H-benzimidazol-2-yl)-3-(3-nitrophenyl)-
prop-2-en-1-ylidene]pyrimidine-2,4,6-(1H,3H,5H)-trione
(5e): Pale brown solid, yield 66 %, m.p.-239-240 ºC; IR (KBr)
3227 (N-H str). 1678 (C=O), 1569 (C=N) 1310 (Ar-NO2), 1H
NMR (DMSO-d6 + CDCl3) in δ ppm: 8.5 (1H, s, NH benzimi-
dazole), 8.2-8.4 (2H, s, pyrimidine NH), 6.4-8.4 (10H, m,
8ArH, 2CH=CH). MS: 405.6 (M+2). Calcd./Anal. (%) [C
59.56/59.71, H 3.25/3.29, N 17.36/17.43].
5-[(2E)-1-(1H-benzimidazol-2-yl)-3-(2-hydroxy-
phenyl)prop-2-en-1-ylidene]pyrimidine-2,4,6-(1H,3H,5H)-
trione (5f): Yellow solid, yield 61 %, m.p. 200-203 ºC; IR

1856 Mathew et al.
Asian J. Chem.
TABLE-2
DETERMINATION OF ANTIOXIDANT ACTIVITY OF BARBITONE MOIETIES BY DPPH ASSAY
Compound
code
Absorbance at 517 nm
Absorbance
Am
0.1 mM
0.8735
0.0056
8
0.2 mM
0.7532
0.0037
20.73
0.5 mM
0.6743
0.0023
28.75
0.7 mM
0.5432
0.0011
42.52
1 mM
0.4219
0.0007
55.34
IC50 (mM)
5a
As
% of activity
Am
0.84
0.8652
0.0042
8.71
0.6928
0.0031
26.87
0.5832
0.0019
38.36
0.5128
0.0011
45.74
0.4156
0.0008
56.01
5b
As
% of activity
Am
0.81
0.7435
0.0032
21.50
0.6739
0.0024
28.80
0.4312
.0019
0.3678
0.0011
61.11
0.2932
0.0007
68.98
5c
As
% of activity
Am
54.38
0.42
0.7568
0.0054
20.33
0.6854
0.0032
27.67
0.4976
0.0021
47.46
0.3952
0.0016
58.27
0.3129
0.0011
66.94
5d
As
% of activity
Am
0.46
0.8679
0.0065
8.67
0.7431
0.0042
21.65
0.6552
0.0024
30.78
0.5327
0.0012
43.64
0.4019
0.0004
57.43
5e
5f
As
% of activity
Am
0.75
0.6976
0.0054
26.60
0.5682
0.0039
40.17
0.4367
0.0028
54.00
0.2865
0.0017
69.80
.2182
As
0.0011
76.98
% of activity
Absorbance
% of activity
0.37
0.21
Ascorbic acid
0.5692
39.65
0.4821
48.89
0.2431
74.22
0.1191
87.37
0.0431
95.43
7. R.V. Shingalapur, K.M. Hosamani and R.S. Keri, Eur. J. Med. Chem.,
44, 4244 (2009).
The IC50 and percentage inhibition of the newly synthesized
products were compared with standard ascorbic acid and the
values were shown in Table-2.
8. G.R. Jadhav, M.U. Shaikh, R.P. Kale and C.H. Gill, Eur. J. Med. Chem.,
44, 2930 (2009).
9. M. Shaharyar, M.M. Abdullah, M.A. Bakht and J. Majeed, Eur. J. Med.
Chem., 45, 114 (2010).
Conclusion
In conclusion, we have synthesized some novel benzi-
midazole products incorporated with barbitone moiety and
evaluated for these compounds for their antioxidant activity
by DPPH assay. All the derivatives showed a favourable range
of activity. The products like 5f, 5c and 5d were concluded as
the most potent derivatives among them. This study focused a
relation between scavenging and blood brain barrier prediction
of DEC-I model. It has been concluded than an increase in
this value will not favours for the DPPH scavenging activity
in the titled derivatives except in 5e. Introduction of electron
donating group in the ortho and para position gets less C log
P value and increases the percentage inhibition. Therefore our
research will provide a great impact on the medicinal chemist
for the further research in the benzimidazole connecting
barbituric acid derivatives possessing potent antioxidant and
anticancer activities.
10. M.M. Ramla, M.A. Omar, A.M.M. El-Khamry and H.I. El-Diwani,
Bioorg. Med. Chem., 14, 7324 (2006).
11. Y.H. Yang, M.S. Cheng, Q.H. Wang, H. Nie, N. Liao, J. Wang and H.
Chen, Eur. J. Med.Chem., 44, 1808 (2009).
12. T.D. Penning, G.D. Zhu, V.B. Gandhi, S.J. Gong Thomas, W. Lubisch,
R. Grandel, W. Wernet, C.H. Park, E.H. Fry, X. Liu,Y. Shi, V. Klinghofer,
E.F. Johnson, C.K. Donawho, D.J. Frost, V.B. Diaz, J.J. Bouska, A.M.
Olson and K.C. Marsh, Bioorg. Med. Chem., 16, 6965 (2008).
13. L. Garuti, M. Roberti, D. Pizzirani, A. Pession, E. Leoncini, V. Cenci
and S. Hrelia, Farmaco, 59, 663 (2004).
14. N. Kaur, A. Kaur,Y. Bansal, D.I. Shah, G. Bansal and M. Singh, Bioorg.
Med. Chem., 16, 10210 (2008).
15. A.R. Porcari, R.V. Devivar and L.S. Kucera, J. Med. Chem., 41, 1252 (1998).
16. M.T. Migawa, J.L. Girardet, J.A. Walker 2nd, G.W. Koszalka, S.D.
Chamberlain, J.C. Drach and L.B. Townsend, J. Med. Chem., 41, 1242
(1998).
17. I. Tamm and P.B. Sehgal, Adv. Virus Res., 22, 187 (1978).
18. S. Budavari, The Merck Index, Merck, Rahway, NJ, USA, edn. 11 (1989).
19. Y. Furukawa, Eur. Patent, 22688 (1983).
20. S.L. Katz and A.W. Gay, US Patent 352 806 (1982).
21. W.G. Brouwer, E.E. Felauerand and A.R. Bell, US Patent, 779 982
990 (1991).
ACKNOWLEDGEMENTS
22. A.V. Moskovin, N.R. Reznikova and B.A. Ivin, Russ. J. Org. Chem.,
38, 463 (2002).
The authors are thankful to Grace College of Pharmacy,
Palakkad (India) for providing the research facilities. The authors
are also thanksful to SAIF, IIT Chennai (India) for spectral
analysis.
23. J. Rajora, J. Yadav, R. Kumar and Y.K. Srivastava, Indian J. Chem.,
49B, 989 (2010).
24. H.G. Sangani, K.B. Bhimani, R.C. Khunt and A.R. Parikh, J. Serb.
Chem. Soc., 6, 587 (2006).
25. J.S. Biradar, B.S. Sasidhar and R. Parveen, J. Med. Chem., 45, 4074 (2010).
26. C.A. Lippinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug.
Deliv., 23, 3 (1997).
REFERENCES
1. G.B. Bulkley, Surgery, 113, 479 (1993).
2.
27. D.E. Clark, J. Pharm. Sci., 88, 815 (1999).
28. R. Bartzatt, S.L.G. Cirillo and J.D. Cirillo, Physiol. Chem. Phys. Med.
NMR, 36, 85 (2004).
B. Halliwell and M. Guitteridge, Free Radicals in Biology and Medicine,
edn. 3rd, Oxford Science Publication, Oxford University Press (1998).
3. K.F. Ansari and C. Lal, Eur. J. Med. Chem., 44, 4028 (2009).
4. V.M. Reddy and K.R. Reddy, Chem. Pharm. Bull., 58, 953 (2010).
5. K.F. Ansari and C. Lal, Eur. J. Med. Chem., 44, 2294 (2009).
6. K.G. Desai, and K.R. Desai, Bioorg. Med. Chem., 14, 827 (2006).
29. V. Weber, P. Coudert, C. Rubart and J.C. Garmian, Bioorg. Med. Chem.,
10, 1647 (2002).
30. K. Shimada, K. Fujikawa, K. Yahara and T.J. Nakamura, Agri. Food.
Chem., 40, 945 (1992).