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4.2. Anti-inflammatory activity
Table 6
Anti-inflammatory activity screening of compounds 4d, 4g, 4k, 4l, 4n,
4p and 4s: acute inflammation
The thiazoles (4) were also screened for their anti-
inflammatory activity. The screening was conducted in
two models, acute inflammatory model and chronic
inflammatory model. In acute inflammatory model,
carrageenan induced rat paw oedema method [8] was
used. Carrageenan (an irritant) at a concentration of 1
mg mlꢁ1 was injected subcutaneously into the hind paw
of the rat to produce oedema. Different groups of
animals were administered a standard drug Ibuprofen,
the test samples and the vehicle used for the preparation
of samples .The increase in the paw volume was
measured before and after three hours of administration
and the results were compared.
Group
Paw oedema volume,
meanꢃS.E. (ml)
Percentage of inhibition,
meanꢁS.E. [P]
/
/
Control
Ibuprofen
0.279
0.0
0.059
0.039
0.0159
0.049
0.029
/
0.02
ꢀ/
100%
79.759
89.09
94.59
63.759
92.759
4d
4g
4k
4n
4s
/
0.05
0.03
0.01
0.02
0.02
/
20.25
11
/
/
/
/
5.5
/
/
16.80
7.25
/
/
P B0.05 vs. ibuprofen.
/
cases, the percentage of inhibition was compared with
that of the standard drug Ibuprofen. Interestingly five
compounds 4d, 4g, 4k, 4n and 4s carrying 4-bromophe-
nyl, 4-methylphenyl, 3-chloro-4-fluorophenyl, 4-chloro-
benzylideneamino and 2-nitrophenylfurylideneamino
substituents showed acute anti-inflammatory activity.
Compounds 4d and 4p carrying 4-bromophenyl and 3,4-
methylenedioxybenzylidene amino substituents showed
excellent chronic anti-inflammatory activity comparable
with that of ibuprofen.
Fifty-four healthy albino rats of body weight 100ꢀ200
/
g were selected and made into nine groups of six animals
each. All the animals were kept on fasting for 18 h. One
group of animals was kept as control which received 2%
w/v acacia mucilage which was used to suspend the
sample. Another group received the standard drug
ibuprofen 20 mg kgꢁ1 body weight intraperitonially.
Remaining seven groups of animals received seven
different test compounds (20 mg kgꢁ1 body weight)
intraperitonially. After 30 min 0.1 ml of w/v carrageenan
was injected subcutaneously into the right hind paw of
the rats. A mark was made at the lateral maleous of the
right hind paw which was dipped in the plethismograph
up to the mark and the volume was measured immedi-
ately and after 3 h. The change in paw volume was
compared with that in the vehicle treated control
animals. The percentage inhibition of oedema was
calculated using the formula,
5. Experimental
Melting points were taken in open capillary tubes and
are uncorrected. IR spectra in KBr pellets were recorded
on JASCO FT-IR 5300 Infrared spectrophotometer. 1H-
NMR spectra were recorded in DMSO-d6 on a Varian
(300 MHz) spectrometer using TMS as an internal
standard and the mass spectra were recorded on a
VG-s-70 micro mass, mass spectrometer operating at 70
eV.
%Oedemainhibitionꢂ100ꢁ(Vtest=Vcontrol)ꢄ100:
In chronic inflammatory model, cotton pellet Gran-
uloma method [9] was used. Granuloma represents the
exudative and proliferative phases of inflammation. The
inflammation is measured by weighing the capsular
granuloma together with the cotton pellet. The results
of such studies are given in Tables 5 and 6. In both the
5.1. General procedure for the synthesis of N-substituted
thioureas (1)
Benzoyl chloride (0.01 mol) was added over 5 min to a
freshly prepared solution of ammonium isothiocyanate
(0.012 mol) in reagent grade acetone and the mixture
was heated under reflux for about 15 min. Heating was
stopped and appropriate aniline in acetone was added.
The mixture was heated under reflux for 30 min and
then poured on to crushed ice. The resulting solid was
collected, washed with water, followed by cold mixture
of water and methanol (1:1). Suitably substituted
benzoylthioureas were added to a preheated solution
of aqueous sodium hydroxide (5%) and stirred. The
mixture was then poured onto crushed ice containing
hydrochloric acid (5%). The benzoic acid separated was
removed by treating the reaction mixture with sodium
Table 5
Chronic inflammation
Group
Net wt. of granulation tissue, Percentage of Inhibition,
mean9S.E. mean9S.E. [P]
/
/
Control
Ibuprofen
131.59
/
0
ꢀ
/
72.09
72.259
86.259
110.509
85.759
92.509
71.09
81.879
/
1.25
45.10
45.59
34.59
15.59
34.59
309
45.59
37.59
4d
4g
4k
41
4n
4p
4s
/
33
/
25.5
2.5
8.5
0.5
10
/
3.25
11.25
0.5
/
/
/
/
/
/
13.0
/
/
1.0
/
0.5
/
3.62
/
0.5
Holla, B. Shivarama
