Microwave-assisted synthesis of novel 3,4-Bis-chalcone-N-arylpyrazoles and their anti-inflammatory activity

Article abstract of DOI:10.1002/jccs.201190137

A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-h was prepared conveniently from diacetyl pyrazoles 2a,b. All reactions were carried out under conventional thermal heating and/or microwave irradiation. The structure of the latter functionally pyrazoles wa

Full text of DOI:10.1002/jccs.201190137

Journal of the Chinese Chemical Society, 2011, 58, 863-868
863
Microwave-assisted Synthesis of Novel 3,4-Bis-chalcone-N-arylpyrazoles
and Their Anti-inflammatory Activity
Hatem A. Abdel-Aziz,a,* Khalid A. Al-Rashood,a Kamal Eldin H. ElTahirb and Hany S. Ibrahimc
aDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University,
P.O. Box 2457, Riyadh 11451, Saudi Arabia
bDepartment of Pharmacology, College of Pharmacy, King Saud University,
P.O. Box 2457, Riyadh 11451, Saudi Arabia
cDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University,
Badr City, Cairo 11829, Egypt
Received April 28, 2011; Accepted July 4, 2011; Published Online July 20, 2011
A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-h was prepared conveniently from diacetyl pyra-
zoles 2a,b. All reactions were carried out under conventional thermal heating and/or microwave irradia-
tion. The structure of the latter functionally pyrazoles was confirmed under the bases of their IR, mass, 1H
NMR and 13C NMR. The X-ray diffraction of compound 3e not only confirmed the chemical structure of
3a-h, but also showed the E configuration of their chalcone moieties. Treatment of compound 3e with
phenyl hydrazine in presence of acetic acid afforded the tri-pyrazle 4. The anti-inflammatory activity of
the newly synthesized compounds was investigated. Some of these compounds showed a moderate activ-
ity when compared with indomethacin as a reference drug. The combination between chalcone and
pyrazole moieties revealed a variable effect in anti-inflammatory activity.
Keywords: Microwave-Assisted synthesis; N-arylpyrazoles; Bis-chalcones; Anti-inflammatory ac-
tivity.
INTRODUCTION
NSAIDs (Non-steroidal anti-inflammatory drugs) re-
The combination of both previous active moieties,
pyarazole and chalcone, may provide a synergistic effect to
improve the anti-inflammatory activity. These predictions
encouraged us to synthesize hybrid compounds containing
N-arylpyrazole combined with chalcone scaffold. Based on
the previous findings and in continuation of our interest in
the synthesis of bioactive heterocycles including pyra-
zoles,15-25 we are dealing in this study with the synthesis of
the title compounds using microwave irradiation to evalu-
ate their anti-inflammatory activity.
main among the most widely prescribed drugs world-
wide.1,2 N-arylpyrazoles were found to be a main pharma-
cophore in many NSAIDs3-7 such as the famous anti-in-
flammatory drugs Celecoxib and SC-558.8,9
On the other hand, Chalcone derivatives have a vari-
ety of pharmacological activities such as anti-inflamma-
tory, analgesic and antipyretic activities.10,11 Furthermore,
some chalcones were observed to be excellent anti-inflam-
matory agents.12
The main method for the synthesis of chalcones is the
classical Claisen-Schmidt condensation in the presence of
aqueous alkaline bases. They are obtained also via the
Wittig reaction, by the Friedel-Crafts acylation with cin-
namoyl chloride, or photo-Fries rearrangement of phenyl
cinnamates. Microwave synthesis offered advantages over
conventional heating, due to rapid reaction and improve-
ment in yields, in the synthesis of chalcones.13,14
RESULTS AND DISCUSSION
Pyrazoles 2a,b were synthesized by the reaction of
pentan-2,4-dione with the appropriate 2-oxo-N¢-arylpro-
panehydrazonoyl chloride 1a,b at room temperature in
ethanolic sodium ethoxide.26 Although the pyrazoles 2
have been known for more than three decades26 there is no
any studies for their reactivity except their reaction with
hydrazine hydrate to afford pyrazolo[3,4-d]pyridazine de-
* Corresponding author. Fax: +966 14676220; E-mail: hatem_741@yahoo.com

864 J. Chin. Chem. Soc., Vol. 58, No. 7, 2011
Abdel-Aziz et al.
rivatives.27
Table 1. Reaction time and yield of conventionally and
microwave-assisted synthesis
Microwave irradiation has been used for a rapid and
efficient synthesis of the novel bis-chalcones 3a-h. Thus,
pyrazoles 2a,b were reacted with a series of aldehydes in
10% aqueous sodium hydroxide under microwave irradia-
tion (100W, 60 °C) for 4 min to give the bis-chalcone 3a-h
in good yields (70-93%) (Scheme I). On the other hand,
bis-chalcones 3a-h were prepared conventionally at room
temperature for 12 h (Scheme I). The obtained results of
microwave irradiation synthesis were compared with the
conventional method (Table 1).
Conventionally synthesis
MW-assisted synthesis
Comp.
Time (h)
yield (%) Time (min) Yield (%)
3a-h
6
12
18
54-80
58
4
7
70-93
72
Selected bond distances in compound 3e and the tor-
sion angle of its chalcone double bonds were given in Table
2. The bond lengths and torsion angles of E-configuration
of chalcones in 3e are well within the range that typically
reported for similar chalcones.28
Scheme I
In an attempt to understand the anti-inflammatory po-
tentiality of 3, we synthesized tri-pyrazoles 6. Thus, the
treatment of compound 3e with phenyl hydrazine in re-
fluxing ethanol, in presence of acetic acid, afforded the
tri-pyrazle 6 (Scheme II). The 1H NMR spectrum of com-
pound 6 revealed the characteristic signals of pyrazolines
protons in the regions d 3.07-3.09, 3.90-3.94 and 5.40-
5.43, respectively. Furthermore, compound 6 was prepared
under microwave irradiation (100W, 100 °C) for 7 min to
give 72% yield.
The anti-inflammatory activity of the tested com-
pounds, meloxicam and indomethacin, as reference stan-
dards, was evaluated. Compounds 2a, 3a and 3b revealed
significant activity related to the other tested compounds.
On the other hand, compounds 3c-h and 2b showed a weak
to moderate activity related to the reference drugs while
Table 2. Characteristic bond lengths [Å] and torsion angles [°] of
3e
O
C27
C28
Me
Reagents and conditions: (a), (CH3CO)2CH2, EtONa/EtOH; (b),
2ArCHO, EtOH, 10% NaOH, r.t., stirring, 12 h (for thermal heat-
ing) or 2ArCHO, EtOH, 10% NaOH, 60 °C, 100 W, 4 min (for
microwave irradiation).
C1
C26
N
Me
O
N
C16
C17
C18
C19
The IR spectra of 3a-h showed the appearance of car-
bonyl function absorption bands in the region 1670-1655
cm-1. The 1H NMR spectra of 3a-h displayed the two sig-
nals of E olefinic protons besides the aromatic protons.
However, we confirmed the latter E-configuration struc-
ture by the X-ray single crystal of compound 3e (Fig. 1).
The mass spectra of 3a-h revealed, in each case, a peak cor-
responding to the molecular ion. However, all attempts to
isolate any of mono chalcones 4 or 5 were failed.
bond length [Å]
C16–C17
C17–C18
C18–C19
1.473
C1–C26
1.466
1.334
1.488
1.324
1.463
C26–C27
C27–C28
torsion angles [°]
C16–C17–C18–C19
C1–C26–C27–C28
178.96
171.70
(E)
(E)

3,4-Bis-chalcone-N-arylpyrazoles
J. Chin. Chem. Soc., Vol. 58, No. 7, 2011 865
Fig. 1. (a) X-ray structure of 3e; (b) View of 3e, hydrogen atoms are omitted for clarity.
compound 6 showed no activity as shown in Table 3.
The combination between chalcone moiety and pyr-
azole ring 2a was found to increase the activity when com-
pared to 3a or 3b. The latter combination slightly decreased
the activity in the case of 3c and 3d. Similarly, the chal-
cones 3e, 3f and 3g showed activity higher than the parent
pyrazole 2b while chalcone 3h revealed slightly lower ac-
tivity than 2b. Furthermore, the pyrazoles with N-(phenyl)-
pyrazoles, have lower anti-inflammatory activity than that
of N-(4-methylphenyl)pyrazoles. However, compound 3a
was the best among the tested compounds, it reduced the
Scheme II
Reagents and conditions: (a), PhNHNH2, EtOH/AcOH, reflux 18
h, 58% (for thermal heating) or 100 °C, 100 W, 7 min, 72% (for
microwave irradiation).
Table 3. Anti-inflammatory results of the tested compounds
3 h
6 h
Before injection
Group
% Edema
% Edema
inhibition
Edema vol.
Edema vol.
Pot. (%)
Edema vol.
Pot. (%)
inhibition
Control
2a
0.289 0.018
0.254 0.014
0.245 0.010
0.319 0.009
0.265 0.009
0.243 0.006
0.253 0.013
0.239 0.006
0.245 0.010
0.256 0.010
0.254 0.010
0.247 0.009
0.279 0.009
0.263 0.016
0.475 0.012
0.383 0.016a
0.407 0.019
0.439 0.013
0.389 0.019a
0.383 0.019a
0.386 0.023
0.371 0.013b
0.380 0.013a
0.356 0.026c
0.422 0.019
0.452 0.020
0.385 0.017a
0.364 0.010b
-
0
0.475 0.012
0.379 0.030b
0.404 0.015
0.433 0.016
0.383 0.016c
0.376 0.019b
0.385 0.016a
0.369 0.010b
0.391 0.015
0.405 0.011
0.419 0.021
0.447 0.002
0.375 0.018b
0.358 0.017c
-
0
30.23
12.49
35.58
32.69
24.37
28.15
28.72
27.43
21.23
9.69
65.98
27.26
77.66
71.35
53.20
61.45
62.69
59.87
46.35
21.14
0.00
32.43
13.95
38.90
35.92
28.31
28.61
30.16
21.38
25.92
11.33
0.00
66.41
28.57
79.67
73.56
57.97
58.60
61.76
43.78
53.08
23.20
0.00
2b
3a
3b
3c
3d
3e
3f
3g
3h
6
0.00
42.65
45.81
Meloxicam
Indomethacin
93.10
100
48.25
48.83
98.82
100
The potency (pot.) was calculated compared to the reference drug indomethacin.
Significance levels a, P < 0.05; b, P < 0.01 and c, P < 0.001 as compared with control.

866 J. Chin. Chem. Soc., Vol. 58, No. 7, 2011
Abdel-Aziz et al.
1
volume of edema by 38.90% after 6 h with 79.67% potency
respect to the reference drug indomethacin.
(KBr) nmax/cm-1 1655 (2C=O), 1590 (C=N); H NMR
(DMSO-d6) d 2.36 (s, 3H, -CH3), 3.79 (s, 3H, -OCH3), 3.81
(s, 3H, -OCH3), 6.97-7.12 (m, 5H, ArH), 7.47-7.79 (m,
12H, ArH); 13C NMR d 11.96 (-CH3), 55.91 (2 -OCH3),
115.02, 115.10, 121.24, 122.68, 126.12, 126.20, 127.55,
127.68, 129.74, 130.05, 130.91, 131.23, 138.79, 142.6,
143.10, 144.44, 149.85, 161.76, 162.06, 184.78 (-C=O),
189.08 (-C=O); MS m/z (%) 478 (M+, 0.29), 281 (43.94),
207 (100), 73 (26.87). Anal. Calcd for C30H26N2O4
(478.54): C, 75.30; H, 5.48; N, 5.85. Found: C, 75.51; H,
5.66; N, 5.98.
EXPERIMENTAL
Melting points (°C, uncorrected) were determined us-
ing a Gallenkamp melting point apparatus. The IR spectra
(KBr) were recorded on a PerkinElmer FT/IR spectrome-
ter. The NMR spectra were recorded at 400 MHz on a Jeol
spectrometer using tetramethylsilane as an internal stan-
dard. 1H and 13C spectra were run at 400 and 100 MHz, re-
spectively. Chemical shift (d) values are given in parts per
million and coupling constants (J) in Hertz. The mass spec-
tra were performed using a Varian MAT CH-5 spectrometer
(70 eV). Microwave experiments were carried out using a
CEM microwave reactor, USA.
1,1¢-(5-Methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(3-(4-
chlorophenyl)prop-2-en-1-one) (3c)
White powder, 75% yield; mp 195-197 °C; IR (KBr)
nmax/cm-1 1662 (2C=O), 1598 (C=N); 1H NMR (DMSO-d6)
d 2.38 (s, 3H, CH3), 7.23-7.86 (m, 17H, ArH); MS m/z (%)
487 (M+, 0.95), 207 (100). Anal. Calcd for C28H20Cl2N2O2
(487.38): C, 69.00; H, 4.14; N, 5.75. Found: C, 69.17; H,
4.35; N, 5.91.
Synthesis of bis chalcones 3a-h
Microwave synthesis
To a solution of the appropriate pyrazole 2a,b (1
mmol) and the appropriate aldehyde (2 mmol) in ethanol
(10 mL), 10% aqueous sodium hydroxide (1 mL) was irra-
diated under microwave irradiation at 100W and 60 °C for
4 min. The reaction mixture was cooled. The resulting solid
was filtered off, washed with water, dried and crystallized
from EtOH/DMF to afford chalcones 3a-c.
1,1¢-(5-Methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(3-
(furan-2-yl)prop-2-en-1-one) (3d)
Beige powder, 70% yield; mp 187-189 °C; IR (KBr)
1
nmax/cm-1 1665, 1654 (2C=O), 1604 (C=N); H NMR
(DMSO-d6) d 2.36 (s, 3H, CH3), 6.66-6.69 (m, 2H, ArH),
6.90 (d, 1H, J = 15.88 Hz, ArH), 6.98 (d, 1H, J = 3.64 Hz,
ArH), 7.08 (d, 1H, J = 3.64 Hz, ArH), 7.35 (d, 1H, J = 15.88
Hz, ArH), 7.49-7.71 (m, 7H, ArH), 7.88 (d, 2H, J = 12.20
Hz, ArH); 13C NMR d 11.95 (-CH3), 112.54, 113.61,
113.78, 117.43, 118.33, 120.19, 125.15, 126.17, 129.56,
129.84, 129.92, 130.08, 130.65, 146.68, 147.07, 151.32,
151.46, 184.10 (-C=O), 188.25 (-C=O); MS m/z (%) 398
(M+, 3.1), 207 (100). Anal. Calcd for C24H18N2O4 (398.41):
C, 72.35; H, 4.55; N, 7.03. Found: C, 72.44; H, 4.72; N,
7.31.
Conventional synthesis
To a stirred solution of the appropriate pyrazole 2a,b
(10 mmol) and the appropriate aldehyde (20 mmol) in etha-
nol (30 mL), 10% aqueous sodium hydroxide (10 mL) was
added portion-wise at room temperature for 10 min, the re-
action mixture was further stirred for 12 h. The resulting
solid was filtered off, washed with water, dried and crystal-
lized from EtOH/DMF to afford chalcones 3a-c.
1,1¢-(5-Methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(3-
phenylprop-2-en-1-one) (3a)
Pale yellow crystals, 70% yield; mp 170-172 °C; IR
1,1¢-(5-Methyl-1-(4-tolyl)-1H-pyrazole-3,4-diyl)bis(3-
phenylprop-2-en-1-one) (3e)
1
(KBr) nmax/cm-1 1661 (2C=O), 1596 (C=N); H NMR
(DMSO-d6) d 2.38 (s, 3H, -CH3), 7.24-7.84 (m, 19H, ArH);
13C NMR d 11.98 (-CH3), 122.58, 123.59, 126.23, 128.36,
129.08, 129.29, 129.53, 129.62, 129.84, 130.07, 131.01,
131.39, 134.92, 135.14, 138.72, 142.83, 143.58, 144.47,
149.69, 184.80 (-C=O), 189.07 (-C=O); MS m/z (%) 418
(M+, 0.50), 281 (27.90), 207 (100), 73 (43.92). Anal. Calcd
for C28H22N2O2 (418.49): C, 80.36; H, 5.30; N, 6.69.
Found: C, 80.56; H, 5.21; N, 6.82.
Pale yellow crystals, 88% yield; mp 156-158 °C; IR
1
(KBr) nmax/cm-1 1662 (2C=O), 1598 (C=N); H NMR
(DMSO-d6) d 2.36 (s, 3H, -CH3), 2.43 (s, 3H, -CH3),
7.23-7.83 (m, 18H, ArH); 13C NMR d 11.95 (-CH3), 21.30
(-p-CH3), 122.48, 123.62, 126.04, 128.36, 129.08, 129.27,
129.53, 129.63, 130.45, 131.00, 131.39, 134.92, 135.14,
136.29, 139.57, 142.77, 143.54, 144.41, 149.56, 184.81
(-C=O), 189.07 (-C=O); MS m/z (%) 432 (M+, 0.46), 281
(28.18), 207 (100), 73 (52.93). Anal. Calcd for C29H24N2O2
(432.51): C, 80.53; H, 5.59; N, 6.48. Found: C, 80.71; H,
5.82; N, 6.69.
1,1¢-(5-Methyl-1-phenyl-1H-pyrazole-3,4-diyl)bis(3-(4-
methoxyphenyl)prop-2-en-1-one) (3b)
Pale yellow crystals, 78% yield; mp 121-125 °C; IR

3,4-Bis-chalcone-N-arylpyrazoles
J. Chin. Chem. Soc., Vol. 58, No. 7, 2011 867
Crystallographic data for the structure 3e has been
deposited with the Cambridge Crystallographic Data Cen-
tre (CCDC) under the number 813247. Copies of the data
can be obtained, free of charge, on application to CCDC 12
Union Road, Cambridge CB2 1EZ, UK [Fax: 44-1223-
336033; e-mail: deposit@ccdc.cam.ac.uk or http://www.
ccdc.cam.ac.uk].
Synthesis of 3,3¢-(5-Methyl-1-(4-tolyl)-1H-pyrazole-3,4-
diyl)bis(1,5-diphenyl-4,5-dihydro-1H-pyrazole) (6)
To a solution of chalcone 3e (0.43 g, 1 mmol) in abso-
lute ethanol (15 mL), phenyl hydrazine (0.22 g, 2 mmol)
and acetic acid (0.5 mL) were added. The reaction mixture
was irradiated under microwave irradiation for 7 min at
100W and 60 °C then left to cool and the solid mass sepa-
rated out was filtered off, washed with ethanol and recrys-
tallized from ethanol to give compound 6 as beige powder
in 72% yield. Compound 6 was prepared conventionally by
refluxing a mixture of chalcone 3e (0.43 g, 1 mmol) in ab-
solute ethanol (30 mL), phenyl hydrazine (0.22 g, 2 mmol)
and acetic acid (0.5 mL). The reaction mixture was re-
fluxed for 18 h then left to cool and the solid mass separated
out was filtered off, washed with ethanol and recrystallized
from ethanol to give compound 6 as beige powder in 58%
yield; mp 180-182 °C; IR (KBr) nmax/cm-1 1597 (C=N); 1H
NMR (DMSO-d6) d 2.39 (s, 3H, -CH3), 2.54 (s, 3H, -CH3),
3.07-3.09 (m, 2H, CH pyrazoles), 3.90-3.94 (m, 2H, CH
pyrazoles), 5.40-5.43 (m, 2H, CHpyrazoles), 6.97-7.44 (m,
24H, ArH); MS m/z (%) 612 (M+, 100). Anal. Calcd for
C41H36N6 (612.76): C, 80.36; H, 5.92; N, 13.71. Found: C,
80.56; H, 6.08; N, 13.94.
1,1¢-(5-Methyl-1-(4-tolyl)-1H-pyrazole-3,4-diyl)bis(3-(4-
methoxyphenyl)prop-2-en-1-one) (3f)
Pale yellow crystals, 93% yield; mp 146-148 °C; IR
1
(KBr) nmax/cm-1 1664 (2C=O), 1596 (C=N); H NMR
(DMSO-d6) d 2.34 (s, 3H, -CH3), 2.42 (s, 3H, -CH3), 3.79
(s, 3H, -OCH3), 3.80 (s, 3H, -OCH3), 6.96-7.11 (m, 5H,
ArH), 7.41-7.78 (m, 11H, ArH); 13C NMR d 11.93 (-CH3),
21.29 (-p-CH3), 55.90 (-p-OCH3), 55.94 (-p-OCH3),
115.01, 115.09, 121.28, 122.58, 126.01, 126.12, 127.55,
127.69, 130.42, 130.89, 131.20, 136.36, 139.44, 142.87,
143.07, 144.35, 149.71, 161.75, 162.05, 184.79 (-C=O),
189.05 (-C=O); MS m/z (%) 492 (M+, 0.52), 281 (26.88),
207 (100), 73 (32.88). Anal. Calcd for C31H28N2O4
(492.57): C, 75.59; H, 5.73; N, 5.69. Found: C, 75.84; H,
5.95; N, 5.81.
1,1¢-(5-Methyl-1-(4-tolyl)-1H-pyrazole-3,4-diyl)bis(3-(4-
chlorophenyl)prop-2-en-1-one) (3g)
Anti-inflammatory activity
White powder, 79% yield; mp 221-225 °C; IR (KBr)
nmax/cm-1 1670 (2C=O), 1608 (C=N); 1H NMR (DMSO-d6)
d 2.36 (s, 3H, -CH3), 2.43 (s, 3H, -CH3), 7.25-7.85 (m,
16H, ArH); MS m/z (%) 501 (M+, 1.6), 207 (100). Anal.
Calcd for C29H22Cl2N2O2 (501.40): C, 69.47; H, 4.42; N,
5.59. Found: C, 69.63; H, 4.65; N, 5.83.
Edema was induced in the right hind paw of adult al-
bino 90 rats (120-150 g) by the subcutaneous injection of
0.1 mL 2% carrageenan sodium (Sigma, USA) in water.
Both sexes were used but pregnant females were excluded.
Each group was composed of 6 animals. The animals were
obtained from animal house laboratory of Nile Company,
Cairo, Egypt and acclimatized for 1 week in the animal fa-
cility that has 12 h light/dark cycles with the temperature
controlled at 21-23 °C. The rats were starved for 18 h and
water was provided ad libitum. The tested compounds, af-
ter complete dissolution in EtOH/Tween 80-H2O (2:2:20
v/v/v), and meloxicam were administered by oral route di-
rectly after injection of the carrageenan at a dose of 10
mg/kg. Indomethacin was given by oral route at 5 mg/kg
body weight. This dose of indomethacin was considered as
a positive control for experiments with any new chemical
entity. The volume of the rat’s paw was measured 3 and 6 h
after injection of carrageenan using Dial micrometer model
(120-1206 Baty, Sussex, England). The reported values
were expressed as volume of edema at each time interval,
percentage inhibition of edema volume at each time with
respect to control and potency which was calculated com-
1,1¢-(5-Methyl-1-(4-tolyl)-1H-pyrazole-3,4-diyl)bis(3-
(furan-2-yl)prop-2-en-1-one) (3h)
Beige powder, 80% yield; mp 140-142 °C; IR (KBr)
1
nmax/cm-1 1669, 1657 (2C=O), 1600 (C=N); H NMR
(DMSO-d6) d 2.34 (s, 3H, -CH3), 2.43 (s, 3H, -CH3),
6.65-6.69 (m, 2H, ArH), 6.90 (d, 1H, J = 15.88 Hz, ArH),
6.98 (d, 1H, J = 3.68 Hz, ArH), 7.08 (d, 1H, J = 3.64 Hz,
ArH), 7.34 (d, 1H, J = 15.24 Hz, ArH), 7.42-7.63 (m, 6H,
ArH), 7.88 (d, 2H, J = 13.44 Hz, ArH); 13C NMR d 11.91
(-CH3), 21.29, (-CH3), 113.58, 113.76, 117.38, 118.28,
120.24, 122.25, 125.16, 125.96, 129.47, 130.45, 130.59,
136.28, 139.54, 143.56, 146.65, 147.04, 149.25, 151.33,
151.47, 184.08 (-C=O), 188.46 (-C=O); MS m/z (%) 412
(M+, 3.6), 207 (100). Anal. Calcd for C25H20N2O4 (412.44):
C, 72.80; H, 4.89; N, 6.79. Found: C, 72.96; H, 4.98; N,
6.87.

868 J. Chin. Chem. Soc., Vol. 58, No. 7, 2011
Abdel-Aziz et al.
pared to indomethacin.29 Data of anti-inflammatory study
were expressed as value SEM in. Differences between
vehicle control and treatment groups were tested using
one-way ANOVAfollowed by multiple comparisons by the
Bonferroni’s test.
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