2-(3-Methyl-1-phenyl-1 H-pyrazol-4-yl)-3-phenylthiazolidin-4-ones as potent antioxidant and antidiabetic agent

Article abstract of DOI:10.14233/ajchem.2014.17003

A series of 2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-ones (7a-7j) were synthesized by intramolecular cyclization of imines (6a-6j) with thioglycolic acid in the presence of acid catalyst. The Schiff bases were obtained upon reaction between electrophilic carbon atom of 3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (4) and nucleophilic nitrogen atom of substituted aromatic amines. in vitro Antioxidant activity was determined by DPPH redical scavenging assay mehod using ascorbic acid as standard. The antidiabetic activity was carried out by streptazocine induced diabetic method using rosiglitazone as standard drug on wister rats. From the study it were found that 3-(4-chlorophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazolidin-4-one (7a), 3-(4-bromophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazolidin-4-one (7b), 3-(3,4-dichlorophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazolidin-4-one (7d ), 3-(3,4-difluorophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazolidin-4-one (7f) 2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-(4-(trifluoromethyl) phenyl) thiazolidin-4-one (7h), 3-(4-methoxyphenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl) thiazolidin-4-one (7j) shown more IC₅₀compare to standard. Where as compound 7a, 7b, 7h, 7j show more significant antidiabetic effect against hyperglycemic rats compare to standard drugs at the dose of 5 mg/kg after 21 days of treatment.

Full text of DOI:10.14233/ajchem.2014.17003

Asian Journal of Chemistry; Vol. 26, No. 19 (2014), 6616-6622
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17003
2
-(3-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-ones as
Potent Antioxidant and Antidiabetic Agent
1
,*
2
1
SANDIP SEN , BIPLAB DE and T.S. EASWARI
1
2
IIMT College of Medical Sciences, O. Pocket, Ganga Nagar, Meerut-250 001, India
Regional Institute of Pharmaceutical Science and Technology, Abhoynagar, Agartala-799 006, India
*
Corresponding author: E-mail: sandipsen2010@gmail.com
Received: 7 January 2014; Accepted: 22 February 2014;
Published online: 16 September 2014;
AJC-15974
A series of 2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-ones (7a-7j) were synthesized by intramolecular cyclization
of imines (6a-6j) with thioglycolic acid in the presence of acid catalyst. The Schiff bases were obtained upon reaction between electrophilic
carbon atom of 3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (4) and nucleophilic nitrogen atom of substituted aromatic amines. in vitro
Antioxidant activity was determined by DPPH redical scavenging assay mehod using ascorbic acid as standard. The antidiabetic activity
was carried out by streptazocine induced diabetic method using rosiglitazone as standard drug on wister rats. From the study it were found
that 3-(4-chlorophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazolidin-4-one (7a), 3-(4-bromophenyl)-2-(3-methyl-1-phenyl-1H-
pyrazol-4-yl)thiazolidin-4-one (7b), 3-(3,4-dichlorophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazolidin-4-one (7d), 3-(3,4-
difluorophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazolidin-4-one (7f) 2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-(4-
(trifluoromethyl) phenyl) thiazolidin-4-one (7h), 3-(4-methoxyphenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-yl) thiazolidin-4-one (7j) shown
more IC50 compare to standard. Where as compound 7a, 7b, 7h, 7j show more significant antidiabetic effect against hyperglycemic rats
compare to standard drugs at the dose of 5 mg/kg after 21 days of treatment.
Keywords: Pyrazole-4-carboxaldehydes, Thiazolidine-4-one, Antioxidant, Antidiabetic.
also been shown to alter lipid profiles in patients with type 2
diabetes. They also have shown a decrease in triglyceride
4
levels, increase in total and LDL cholesterol levels . In patients
INTRODUCTION
Among the wide variety of heterocyclic compounds
pyrazoles fused with different heterocycles known to contribute
various pharmacological effects. Due to wide range of pharma-
cological activity there were significant amount of research
activity directed towards this class. In particular, they were
used as antitumor, antibacterial and antifungal, antiviral, anti-
parasitic, antitubercular and insecticidal agents. Some of these
compounds have also shown antiinflammatory, antidiabetic,
receiving insulin therapy, the addition of a thiazolidinedione
has resulted in significant reductions in daily insulin require-
5,6
ments . The thiazolidine were dependent on the presence of
insulin for activity; however, they do not affect insulin secretion.
It was also found that patients with chronic pancreatitis had
high risk of antioxidant deficiencies. Furthermore, this disease
can lead to diabetes mellitus that could exacerbate the severity
of oxidative stress. Oxidative stress and the resulting LDL
1
anesthetic and analgesic properties . Another heterocyclic
compound thiazolidine is a 5 membered saturated ring with a
thio ether group at position 1 and an amino group at the position
7
oxidation considered major cause of atherosclerosis .
3. It has fungicidal, local anesthetic, antiseizure, antitubercular,
antibacterial, antiamoebic, antidiabetic and antiinflammatory
EXPERIMENTAL
2
,3
activities . Thiazolidinones are derivatives of thiazolidine,
which is a main pharmacophoric group responsible for anti-
diabetic activity. It acted by enhancing insulin sensitivity in
both muscle and adipose tissue and to a lesser extent by inhi-
biting hepatic glucose production. These agents have a notable
effect on improving insulin resistance, particularly when used
in combination with other antidiabetic drugs, but have no effect
on insulin secretion. As a class, the thiazolidinediones have
All the chemicals used for the synthesis were reagent grade
and of Sigma Aldrich and Merck Laboratory. The solvents
were purified by standard laboratory procedure and free from
atmospheric oxygen. The melting points were determined by
open capillary method and were not corrected. The IR spectra
were recorded in KBr pellets on a Shimadzu 8201 PC FTIR
1
13
spectrophotometer. Both H and C NMR were recorded in
DMSO-d using Bruker 500 MHz-NMR spectrophotometers
6

Vol. 26, No. 19 (2014)
3-Phenylthiazolidin-4-ones Derivatives as Potent Antioxidant and Antidiabetic Agent 6617
using TMS as internal standard. The masses of the compound
were analyzed by ESI-mass method using Thermo Fennigan
mass spectrophotometer. Elemental analyses were recorded
using Thermo Finnigan FLASH EA 1112 CHN analyzer. TLC
was performed in precoated plastic sheet of silica gel g/UV-
4-Nitro-N-[(3-methyl-1-phenyl-1H-pyrazol-4-yl)-
methylene]benzenamine (6c): Yield: 87 %; m.p. 95-97 °C;
-1
IR (KBr, νmax, cm ): 2953.52 (-CH
1540.02 (C-NO , str), 1450.35 (-CH
, δ ppm): 12.9 (s, 1H, -NH), 7.43 (s, 1H, -N=CH-), 7.33 (s,
5H), 7.20-7.18 (d, 2H, J = 10 Hz, Ar-H), 7.15 (s, 1H, Ar-H),
3
, str), 1685.73 (C=N, str),
1
2
3
, def). H NMR (DMSO-
d
6
2
54 of 0.2 mm thickness.
13
Synthesis of 3-methyl-1-phenyl-1, 2-dihydropyrazol-
-one (3): 1 Mole of phenyl hydrazine was taken in 500 mL
6
6.8-6.78 (d, 2H, J = 10 Hz, Ar-H); C NMR (DMSO-d , δ
5
ppm): 162.1, 147.5, 145.2, 143.4, 136.7, 133.8, 131.4, 130.7,
130.7, 129.4, 129.4, 126.3, 121.7, 121.7, 118.2, 105.7; ESI
+
mass (m/z): 306.11 (M ). Anal. (%) calcd. (found) for
beaker. 1 Mole equivalent of ethyl acetoacetate was added and
allowed to warm the mixture at 100 °C on water bath for 3 h.
Cooling of the mixture at room temperature resulted solidi-
fication of crystal. Washing was taken place with ether and
C
17
H
14
N
4
O
2
: C-60.02 (59.89); H- 4.61 (4.41), N-18.21(18.19).
3, 4-Dichloro -N-[(3-methyl-1-phenyl-1H-pyrazol-4-yl)-
methylene]benzenamine (6d): Yield: 88 %; m.p. 83-84 °C;
8
recrystallized from hot ethanol . Yield: 93 %; m.p. 193-194
1
C; H NMR (DMSO-d
-1
°
6
, δ ppm): 7.18 (m, 2H, Ar-H), 6.71-
IR (KBr, νmax, cm ): 2927.14 (-CH
1679.67 (C=N, str), 764.21 (C-Cl, str); H NMR (DMSO-d ,
3 3
, str), 1434.24 (-CH , def),
1
6
.69 (d, 1H, J = 10 Hz, Ar-H), 6.66-6.64 (d, 2H, J = 10 Hz,
Ar-H), 5.18 (s, 1H, Ar-H of pyrazole), 2.15 (s, 1H, -NH- of
pyazole), 1.17 (s, 3H, -CH of pyrazole).
6
δ ppm): 12.7(s, 1H, -NH), 7.53 (s, 1H, -N=CH-), 7.35 (s, 1H,
Ar-H), 7.31 (s, 5H), 7.2-7.18 (d, 2H, J = 10 Hz, Ar-H), 7.11-
3
13
Synthesis of 3-methyl-1-phenyl-1H-pyrazole-4-carbal-
dehyde (4): Taken 3 mole of 3-methyl-1-phenyl-1,2-dihydro-
pyrazol-5-one (3) in round bottom flask and was added 3 mole
6
7.09 (d, 1H, J = 10 Hz, Ar-H); C NMR (DMSO-d , δ ppm):
161.1, 148.5, 145.2, 143.3, 135.7, 132.8,131.4, 130.5, 130.5,
129.2, 129.2, 126.3, 121.7, 121.7, 118.2,105.7; ESI mass (m/z):
+
of DMF and 1 mole of POCl . During addition of POCl
3
3
the
329.02 (M );Anal. (%) calcd. (found) for C17
(61.70), H- 3.97 (3.62), N-12.73(12.51).
13 3 2
H N Cl : C-61.83
temperature of reaction mixture was maintained 0-5 °C. After
completion of addition reflux the mixture for 6 h.Added sodium
hydroxide and was cool for overnight.After addition of crushed
ice formation of precipitation was taken place. Recrystallized
4-Chloro-N-((3-methyl-1-phenyl-1H-pyrazol-4-yl)-
methylene)-3-nitrobenzenamine (6e): Yield: 78 %; m.p. 93-
-
1
94 °C; IR (KBr, cm ): 2927.34 (-CH
str); 1436.14 (-CH , def), 1683.67 (C=N, str), 764.21 (C-Cl, str);
H NMR (DMSO-d , δ ppm): 12.17(s, 1H, -NH), 7.43 (s, 1H,-
N=CH-), 7.37 (s, 1H, Ar-H), 7.31 (S, 5H), 7.21-7.18 (d, 2H, J =
3 2
, str); 1515.02 (C-NO ,
9
1
from hot ethanol . Yield: 83 %; m.p. 146-147 °C; H NMR
DMSO-d , δ ppm): 8.52 (s, 1H, -CHO), 7.82 (s, 1H, Ar-H);
.31 (s, 6H, Ar-H); 2.79 (s, 3H, -CH of pyrazole).
Synthesis of N-((3-methyl-1-phenyl-1H-pyrazol-4-yl)
3
1
(
6
6
7
3
13
15 Hz, Ar-H), 7.07-7.05 (d, 1H, J = 10 Hz, Ar-H); C NMR
(DMSO-d , δ ppm): 161.6, 148.7, 145.2, 143.3, 135.7, 132.7,
131.4, 130.3, 130.3, 129.1, 129.1, 126.3, 121.7, 121.7, 118.5,
10
methylene) benzenamine (6) : 1 mmol equivalent of 3-me-
thyl-1-phenyl-1H-pyrazole-4-carbaldehyde (4) was added in
6
+
5
0 mL of ethanol. Stirred the reaction mixture for 1 h under
105.3; ESI-MS (m/e): 340.07 (M ). Anal. (%) calcd. (found) for
nitrogen atmosphere. Added 1 mmol of glacial acetic acid.
After that added substituent aromatic amines in 1 mmol equiva-
lent and refluxed for 1 h. Then added crushed ice, filter the
precipitate. Dried at room temperature and recrystallized from
C
17
H
13
N
4
O
2
Cl: C-59.92 (59.79), H-3.85 (3.81), N-16.44 (16.21).
3,4-Difluoro-N-[(3-methyl-1-phenyl-1H-pyrazol-4-
yl)methylene]benzenamine (6f):Yield-68 %; m.p. 81-82 °C;
-1
IR (KBr, νmax, cm ): 2925.14 (-CH
str), 1432.24 (-CH , def), 1681.67 (C=N, str), 1363.21 (C-F,
str); H NMR (DMSO-d , δ ppm): 13.17 (s, 1H, -NH), 7.41 (s,
3 2
, str), 1534.34 (C-NO ,
10
hot ethanol .
3
1
4
-Chloro-N-[(3-methyl-1-phenyl-1H-pyrazol-4-yl)-
6
methylene]benzenamine (6a): Yield: 93 %; m.p. 85-86 °C;
1H, -N=CH-), 7.32 (s, 1H, Ar-H), 7.3 (S, 5H), 7.22-7.20 (d,
13
2H, J = 15 Hz, Ar-H), 7.17-7.15 (d, 1H, J = 10 Hz, Ar-H); C
-1
IR (KBr, νmax, cm ): 2955.34(-CH
671.67 (C=N, str), 664.21 (C-Cl, str); H NMR (DMSO-d
δ ppm): 13.7 (s, 1H, -NH ), 7.52 (s, 1H, -N=CH-), 7.31 (s,
3
, str), 1450.14 (-CH
3
, def),
1
1
6
,
6
NMR (DMSO-d , δ ppm): 161.5, 148.5, 145.1, 143.2, 135.5,
132.1, 131.1, 130.7, 130.7, 129.1, 129.1, 126.3, 121.7, 121.7,
+
118.5,105.4; ESI-MS (m/e): 297.07 (M ); Anal. (%) calcd.
5
6
1
1
2
H), 7.2-7.18 (d, 2H, J = 10 Hz, Ar-H), 7.15 (s, 1H, Ar-H),
13
.8-6.78 (d, 2H, J = 10 Hz,Ar-H); C NMR (DMSO-d , δppm):
6
(found) for C17
14.13 (14.12).
13 3 2
H N F : C-68.68 (68.28), H-4.41 (3.51), N-
60.1, 147.1, 145.5, 141.4,139.7, 132.8,131.4, 130.2, 130.2,
29.4, 129.4, 126.3, 123.7, 123.7, 120.2, 105; ESI-Mass (m/z):
2-Fluoro-N-[(3-methyl-1-phenyl-1H-pyrazol-4-
yl)methylene]-5-nitrobenzenamine (6g): Yield-79 %; m.p.
+
95.09 (M ).Anal. (%) calcd. (found) for C17
H
14
3
N Cl: C-69.03
-
1
(
68.89), H- 4.77 (4.37), N-14.21(14.11).
-Bromo-N-[(3-methyl-1-phenyl-1H-pyrazol-4-yl)-
methylene]benzenamine (6b): Yield: 92 %; m.p. 85-86 °C;
93-94 °C; IR (KBr, νmax, cm ): 2927.14 (-CH
(C-NO , str) 1433.24 (-CH , def); 1680.67 (C=N, str); 1160.21
(C-F, str). H NMR (DMSO-d , δ ppm): 13.5 (s, 1H, -NH),
3
, str); 1534.34
4
2
3
1
6
-
1
IR (KBr, νmax, cm ): 2956.52 (-CH
624.73 (C=N, str), 621.93 (C-Br, str); H NMR (DMSO-d
δ ppm): 13.7 (s, 1H, -NH ), 7.53 (s, 1H, -N=CH-), 7.21 (s,
3
, str), 1469.35 (-CH
3
, def),
8.2-8.18 (d, 2H, J = 10 Hz, Ar-H), 7.75 (s, 1H, -N=CH-), 7.45
(s, 1H, Ar-H), 7.34 (S, 5H), 7.21-7.19 (d, 2H, J = 10 Hz, Ar-
1
1
6
,
13
H); C NMR (DMSO-d , δ ppm): 163.5, 149.5, 146.1, 143.7,
6
135.7, 132.7, 131.1, 130.7, 130.7, 129.1, 129.1, 126.3, 121.5,
5
6
1
1
H), 7.19-7.18 (d, 2H, J = 5 Hz, Ar-H), 7.15 (s, 1H, Ar-H),
13
+
121.5, 118.5, 105.4; ESI-MS (m/e): 324.07 (M ); Anal. (%)
.8-6.78 (d, 2H, J = 10 Hz,Ar-H); C NMR (DMSO-d , δppm):
6
62.1, 147.5, 145.7, 141.4, 139.7, 132.8,131.4, 130.7,130.7,
calcd. (found) for C17
13 4 2
H N O F: C-62.96 (62.81), H- 4.04
29.4, 129.4, 126.3, 121.7, 121.7, 118.2, 105.7. ESI mass
(4.26), N-17.28 (17.11).
+
m/z): 339.13 (M ); Anal. (%) calcd. (found) for C17
(
C-60.02 (59.89), H- 4.15 (4), N-12.35 (12.27).
H
14
3
N Br:
N-[(3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-4-
(trifluoromethyl)benzenamine (6h):Yield: 95 %; m.p. 101-

6
618 Sen et al.
Asian J. Chem.
-
1
CH
3
OHC
CH
3
1
02 °C; IR (KBr, νmax, cm ): 2927.14 (-CH
-CH , def), 1670.67 (C=N, str), 1136.21 (C-F, str); H NMR
DMSO-d , δ ppm): 13.7(s, 1H, -NH), 7.49 (s, 1H, -N=CH-),
.37 (s, 5H), 7.21-7.18 (d, 2H, J = 15 Hz, Ar-H), 7.15 (s, 1H,
3
, str), 1433.24
1
NHNH2
(
(
3
O
NH POCl3
N
6
ether
+
N
N
O
DMF
O
7
13
2 5
H O
Ar-H), 6.8-6.78 (d, 2H, J = 10 Hz, Ar-H); C NMR (DMSO-
d
1
1
6
, δ ppm): 163.5, 149.5, 146.1, 143.7, 135.7, 132.7, 131.1,
30.7, 130.7, 129.1, 129.1, 126.3, 124.7, 121.5, 121.5, 118.5,
1
2
+
05.4; ESI-MS (m/e): 329.01 (M ); Anal. (%) calcd. (found)
3
4
for C18
14 3 3
H N F : C-65.65 (65.32), H-4.28 (3.39), N-12.76
Ar-NH
2
Ethanol
(
12.49).
N-[(3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene]-4-
nitro-3-(trifluoromethyl)benzenamine (6i):Yield-78 %; m.p.
glacial acetic acid
R
-1
H C
3
CH
N
H
3
C
HC
N
1
08-110 °C; IR (KBr, νmax, cm ): 2935.24 (-CH
C-NO , str), 1336.24 (-CH , def), 1640.67 (C=N, str), 1330.21
C-F, str); H N MR (DMSO-d , δ ppm): 13.1 (s, 1H, -NH),
.12-8.10 (d, 1H, J = 10 Hz, Ar-H), 7.7 (s, 1H, Ar-H), 7.62-
.60 (d, 1H, J = 10 Hz, Ar-H), 7.49 (s, 1H, -N=CH-), 7.31 (S,
3
, str), 1413.02
R
(
(
2
3
S
1
N
N
O
6
TGA/Toluene
N
N
8
7
5
1
1
3
5
13
H), 7.25 (s, 1H, Ar-H); C NMR (DMSO-d , δ ppm): 162.5,
6
49.3, 145.1, 142.7, 135.3, 132.7, 131.1, 130.2, 130.2, 129.3,
7(a-j)
29.3, 126.3, 124.7, 121.5, 121.5, 118.5,105; ESI-MS (m/e):
+
74.02 (M ); Anal. (%) calcd. (found) for C18
6(a-j)
H
13
N
4
2 3
O F : C-
Entry
a,7a 4-chloro
b,7b 4-bromo
6c,7c 4-nitro
6d,7d 3,4-dichloro
R
Entry
R
Entry
R
7.76 (57.46), H- 4.28 (3.39), N-14.97(14.59).
-Methoxy-N-[(3-methyl-1-phenyl-1H-pyrazol-4-yl)
methylene]benzenamine (6j): Yield-78 %; m.p. 95-96 °C;
6
6
6e,7e 3-nitro-4-chloro 6h,7h 4-trifluromethyl
6f,7f 3,4-difluoro 6i,7i 3-trifluoro-4-nitro
4-methoxy
4
6g,7g 2-fluoro-5-nitro 6j,7j
-1
IR (KBr, νmax, cm ): 2824.14 (-CH
3
, str), 2815.22 (-OCH
3
),
, def), 1683.67 (C=N, str); H NMR (DMSO-
, δ ppm): 13.7(s, 1H, -NH), 7.49 (s, 1H, -N=CH-), 7.35 (S,
H), 7.21-7.18 (d, 2H, J = 15 Hz, Ar-H), 7.15 (s, 1H, Ar-H),
1
Scheme-I
1
d
5
6
432.24 (-CH
3
6
3
-(4-Bromophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-
13
4-yl) thiazolidin-4-one (7b): Yield-66 %; m.p. 133-134 °C;
.8-6.78 (d, 2H, J = 10 Hz, Ar-H), 3.73 (s, 3H); C NMR
, δ ppm): 163.5, 149.5, 146.1, 143.7, 135.7, 132.7,
31.1, 130.7, 130.7, 129.1, 129.1, 126.3, 121.5, 121.5, 118.5,
-1
IR (KBr, νmax, cm ): 2953.24 (-CH
463.14 (-CH , def), 1310.33 (C-N, str), 667.21 (C-Br, str);
H NMR (DMSO-d , δ ppm): 12.5 (s, 1H, -NH), 7.31 (s, 5H),
3
, str), 1692.61 (C=O, str),
(
DMSO-d
6
1
1
3
1
1
+
6
05.4, 55.9; ESI-MS (m/e): 291.17 (M ); Anal. (%) calcd.
7
6
1
.21-7.19 (d, 2H, J = 10 Hz, Ar-H), 7.17 (s, 1H, Ar-H), 6.81-
.79 (d, 2H, J = 10 Hz, Ar-H), 4.81 (s, 1H, CH-N), 3.47 (s,
H, CH -C=O), 3.22 (s, 1H, CH
(
17 3
found) for C18H N O: C-74.20 (74.11), H-5.89 (5.62), N-
1
4.42 (14).
Synthesis of 2-(3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-
phenylthiazolidin-4-one (7a-7j): The substituted imines (0.02
mole) were dissolved in toluene, SnCl (0.05 mmol) was used
2
2 3
-C=O), 2.70 (s, 3H, -CH );
13
C NMR (DMSO-d , δ ppm): 171.9, 147.2, 146.5, 142.4,
6
1
1
39.5, 132.7, 131.3, 130.1, 130.1, 129.3, 129.3, 126.7, 123.8,
23.8, 120.1, 105.3, 45.1, 45.1, 11; ESI-MS (m/e): 415.02
2
as catalyst. After addition of thioglycollic acid (0.03 mole)
reaction mixtures were stirred for an hour. The mixtures were
then refluxed in water bath for 12 h and cooled at room tempe-
rature (Scheme-I). Excess solvent were removed by distillation
and compounds were dissolved in dichloromethane. The
organic layer were washed with 10 % sodium-bicarbonate and
finally with brine solutions, dried over sodium sulphate and
evaporated to dryness. Purification of the compounds were
done with petroleum ether and chloroform (2:8 v/v) by chroma-
tographic technique.
+
M ); Anal. (%) calcd. (found) for C13
(
(
12 3
H N OSBr: C-55.08
54.96), H- 3.89 (3.69), N-10.14 (9.92).
-(3-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-(4-nitro-
phenyl)thiazolidin-4-one (7c):Yield-76 %; m.p. 138-139 °C;
2
-
1
IR (KBr, cm ): 2949.24 (-CH
525.02 (C-NO , str), 1461.34 (-CH
H NMR (DMSO-d , δ ppm): 13.7 (s, 1H, -NH), 7.31 (s, 5H),
3
, str), 1701.61 (C=O, str),
1
1
2
3
, def), 1321.33 (C-N, str);
6
7
6
1
d
.21-7.21 (d, 2H, J = 10 Hz, Ar-H), 7.15 (s, 1H, Ar-H), 6.82-
.80 (d, 2H, J = 10 Hz, Ar-H), 4.85 (s, 1H, CH-N), 3.43 (s,
13
H, CH
2 2
-C=O), 3.22 (s, 1H, CH -C=O); C NMR (DMSO-
3-(4-Chlorophenyl)-2-(3-methyl-1-phenyl-1H-pyrazol-4-
yl)thiazolidin-4-one (7a): Yield-68 %; m.p. 143-144 °C; IR
6
, δppm): 171.3, 147.1, 146.3, 141.4, 138.5, 132.5, 131.4,
-1
130.5, 130.5, 129.5, 129.5, 127.7, 124.8, 124.8, 120.1, 105.3,
+
45.3, 45.3, 11.1; ESI-MS (m/e): 380.09 (M );Anal. (%) calcd.
(
KBr, νmax, cm ): 2959.34 (-CH
455.14 (-CH , def), 1260.33 (C-N, str), 760.21 (C-Cl, str); H
NMR (DMSO-d , δ ppm): 13.5 (s, 1H, -NH), 7.33 (s, 5H), 7.2-
.18 (d, 2H, J = 10 Hz, Ar-H), 7.15 (s, 1H, Ar-H), 6.8-6.78 (d,
H, J = 10 Hz, Ar-H), 4.85 (s, 1H, CH-N), 3.49 (s, 1H, CH
3
, str), 1775.67 (C=O, str),
1
1
3
(
found) for C19
4.74 (14.51).
-(3,4-Dichlorophenyl)-2-(3-methyl-1-phenyl-1H-
pyrazol-4-yl)thiazolidin-4-one (7d): Yield-68 %; m.p. 110-
16 4 3
H N O S: C-59.99 (59.70), H-4.24 (4.49), N-
6
1
7
3
2
2
-
13
2 6
C=O), 3.24 (s, 1H, CH -C=O); C NMR (DMSO-d , δ ppm):
-1
1
11 °C; IR (KBr, νmax, cm ): 2948.24 (-CH
C=O, str), 1471.14 (-CH , def), 1321.33 (C-N, str), 764.21
(C-Cl, str); H NMR (DMSO-d , δ ppm): 12.7 (s, 1H, -NH),
.45 (s, 1H, Ar-H), 7.33 (s, 5H), 7.2-7.18 (d, 2H, J = 10 Hz,
3
, str), 1720.61
1
70.9, 147.1, 145.5, 141.4, 139.7, 132.8,131.4, 130.2, 130.2,
(
3
1
29.4, 129.4, 126.3, 123.7, 123.7, 120.2, 105, 45, 45, 11; ESI-
+
1
6
MS (m/e): 369.17 (M ); Anal. (%) calcd. (found) for
OSCl: C-61.70 (61.66), H-4.36 (4.19), N-11.36 (11.12).
7
19 16 3
C H N

Vol. 26, No. 19 (2014)
3-Phenylthiazolidin-4-ones Derivatives as Potent Antioxidant and Antidiabetic Agent 6619
Ar-H), 7.11-7.09 (d, 1H, J = 10 Hz, Ar-H), 4.83 (s, 1H, CH-
2-(3-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-[4-nitro-3-
(trifluoromethyl)phenyl]thiazolidin-4-one (7i):Yield: 88 %;
13
N), 3.41 (s, 1H, CH
DMSO-d , δ ppm): 170.3, 146.1, 143.3, 141.2, 133.5, 132.7,
31.3, 130.2, 130.2, 129.5, 129.5, 126.7, 123.8, 123.8, 120.1,
2 2
-C=O); 3.22 (s, 1H, CH -C=O); C NMR
-1
(
6
m.p. 153-154 °C; IR (KBr, cm ): 2925.24 (-CH
(C=O, str), 1513.02 (C-NO , str), 1436.24 (-CH
(C-F, str), 1321.33 (C-N, str); H NMR (DMSO-d
3
, str), 1720.61
, def), 1330.21
, δ ppm):
1
1
2
3
+
1
08.3, 47.3, 47.3, 11.1; ESI-MS (m/e): 403.15 (M ); Anal.
OSCl : C-56.44 (56.12), H-
6
(
%) calcd. (found) for C19
H
15
N
3
2
13.1(s, 1H, -NH), 8.12-8.10 (δ, 1H, J = 10 Hz, Ar-H), 7.7 (s,
1H, Ar-H), 7.62-7.60 (d, 1H, J = 10 Hz, Ar-H), 7.41 (s, 5H),
3
.74 (3.42), N-10.39(10.11).
-(4-Chloro-3-nitrophenyl)-2-(3-methyl-1-phenyl-1H-
pyrazol-4-yl)thiazolidin-4-one (7e): Yield-63 %; m.p. 149-
3
7.25 (s, 1H, Ar-H), 2.39 (s, 3H, -CH
3.43 (s, 1H, CH -C=O), 3.15 (s, 1H, CH
(DMSO-d , δ ppm): 170.3, 146.1, 143.3, 141.2, 133.5, 132.7,
3
), 4.81 (s, 1H, CH-N),
1
3
2
2
-C=O); C NMR
-
1
1
50 °C; IR (KBr, νmax, cm ): 2948.24 (-CH
C=O, str), 1525.02 (C-NO , str), 1471.14 (-CH
C-N, str), 764.21 (C-Cl, str); H NMR (DMSO-d
2.3 (s, 1H, -NH), 7.43 (s, 5H), 7.35 (s, 1H, Ar-H), 7.2-7.18
d, 2H, J = 10 Hz, Ar-H), 7.11-7.09 (d, 1H, J = 10 Hz, Ar-H),
.85 (s, 1H, CH-N), 3.49 (s, 1H, CH -C=O), 3.25 (s, 1H, CH
, δ ppm): 170.3, 146.1, 143.3,
41.2, 133.5, 132.7, 131.3, 130.2, 130.2, 129.5, 129.5, 126.7,
23.8, 123.8, 120.1, 108.3, 47.3, 47.3, 11.1; ESI-MS (m/e):
3
, str), 1720.61
, def), 1321.33
, δ ppm):
6
(
(
2
3
131.3, 130.2, 130.2, 129.5, 129.5, 126.7, 124.7, 123.8, 123.8,
+
120.1, 108.3, 47.3, 47.3, 11.1; ESI-MS (m/e): 448.07 (M );
1
6
1
Anal. (%) calcd. (found) for C20
15 4 3 3
H N O SF : C-53.57 (53.35),
(
H- 3.53 (3.46), N-12.49 (12.27).
4
2
2
-
3-(4-Methoxyphenyl)-2-(3-methyl-1-phenyl-1H-
pyrazol-4-yl)thiazolidin-4-one (7j): Yield-78 %; m.p. 137-
13
C=O); C NMR (DMSO-d
6
-
1
1
1
4
5
138 °C; IR (KBr, νmax, cm ): 2924.14 (-CH
(-OCH ), 1730.21 (C=O, str), 1432.24 (-CH
(C-N, str); H NMR (DMSO-d
3
, str), 2855.22
, def), 1321.33
, δ ppm): 13.7 (s, 1H, -NH),
3
3
+
1
14.08 (M ); Anal. (%) calcd. (found) for C19
5.01 (54.80), H- 3.64 (3.45), N-13.50(13.11).
-(3,4-Difluorophenyl)-2-(3-methyl-1-phenyl-1H-
pyrazol-4-yl)thiazolidin-4-one (7f): Yield: 63 %; m.p. 163-
15 4 3
H N O SCl: C-
6
7.49 (s, 1H, -N=CH-), 7.37 (s, 5H), 7.21-7.18 (d, 2H, J = 15
Hz, Ar-H), 7.15 (s, 1H, Ar-H), 6.8-6.78 (d, 2H, J = 10 Hz, Ar-
3
H), 4.81 (s, 1H, CH-N), 3.73 (s, 3H), 3.43 (s, 1H, CH -C=O),
2
13
2 6
3.15 (s, 1H, CH -C=O); C NMR (DMSO-d , δ ppm): 170.3,
-1
1
64 °C; IR (KBr, cm ): 2948.24 (-CH
str), 1471.14 (-CH , def), 1321.33 (C-N, str), 1201 (C-F, str);
H NMR (DMSO-d , δ ppm): 12.37(s, 1H, -NH), 7.32 (s, 1H,
Ar-H), 7.29 (s, 5H), 7.23-7.21 (d, 2H, J = 10 Hz, Ar-H), 7.11-
3
, str), 1720.61 (C=O,
3
146.1, 143.3, 141.2, 133.5,132.7,131.3, 130.2, 130.2, 129.5,
129.5, 126.7, 124.7, 123.8, 123.8, 120.1, 108.3, 55.1, 47.3,
+
47.3, 11.1; ESI-MS (m/e): 365.17 (M ); Anal. (%) calcd.
1
6
7
1
d
1
4
.09 (d, 1H, J = 10 Hz, Ar-H), 4.83 (s, 1H, CH-N), 3.48 (s,
(found) for C20
11.50 (11.38).
19 3 2
H N O S: C-65.73 (65.66), H- 5.24 (5.11), N-
13
2 2
H, CH -C=O), 3.15 (s, 1H, CH -C=O); C NMR (DMSO-
6
, δ ppm): 171.3, 145.1, 143.7, 141.3, 135.5, 133.7, 131.8,
30.2, 130.2, 127.5, 127.5, 125.7, 121.8, 121.8, 120.1, 108.3,
Pharmacology
+
5.3, 45.3, 11.4; ESI-MS (m/e): 371.12 (M );Anal. (%) calcd.
Antioxidant activity: The in vitro antioxidant activity
was determined by 1,1-diphenyl-2-picrylhydrazyl radical
method, which was used to evaluate the free radical scavenging
(
found) for C19
N-11.31 (11.11).
-(2-Fluoro-5-nitrophenyl)-2-(3-methyl-1-phenyl-1H-
pyrazol-4-yl) thiazolidin-4-one (7g):Yield: 69 %; m.p. 131-
15 3 2
H N OSF : C-61.44 (61.11), H- 4.07 (3.82),
1
1,12
capacity of different antioxidants
Animals: Wister rat of either sex weighing between 180-
.
3
-1
2
00 g were taken for anti diabetic activity. Animals were
1
32 °C; IR (KBr, nmax, cm ): 2927.14 (-CH
C=O, str), 1534.34 (C-NO , str), 1321.33 (C-N, str), 1433.24
-CH , def), 1160.21 (C-F, str); H NMR (DMSO-δ
3.5 (s, 1H, -NH), 8.2-8.18 (d, 2H, J = 10 Hz, Ar-H), 7.45 (s,
H, Ar-H), 7.39 (s, 5H), 7.21-7.19 (d, 2H, J = 10 Hz, Ar-H),
.81 (s, 1H, CH-N), 3.43 (s, 1H, CH -C=O); 3.15 (s, 1H, CH
, δ ppm): 170.3,146.1, 143.3,
41.2, 133.5, 132.7, 131.3, 130.2, 130.2, 129.5, 129.5, 126.7,
23.8, 123.8, 120.1, 108.3, 47.3, 47.3, 11.1; ESI-MS (m/e):
3
, str), 1720.61
maintained under standard environmental condition at tempe-
rature of 22 ± 2 °C and 45-50 % relative humidity for 24 h
each of dark and light cycle with proper diet. All the studies
were done according to protocol approved by Institutional
Animal Ethical Committee (IAEC) of Bansal College of
Pharmacy (Reg. no-1252/ac/10/CPCSEA, Ref. no-BCP/IAEC/
(
(
2
1
3
6
, δ ppm):
1
1
4
2
2
-
1
3
C=O); C NMR (DMSO-d
6
1
2/02).
Acute toxicity study: The acute oral toxicity study was
carried out according to OECD guideline no 423 in wister
1
1
3
5
+
98.11 (M ); Anal. (%) calcd. (found) for C19
7.28 (57.11), H- 3.79 (3.66), N-14.06 (13.96).
-(3-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-(4-(trifluo-
romethyl) phenyl) thiazolidin-4-one (7h):Yield: 65 %; m.p.
15 4 3
H N O SF: C-
13
rats . The doses were fixed 2 mg/kg (p.o) to 10 mg/kg (p.o)
for rats and contain 5 in each group. The mortality and general
behaviours were under observation for 14 days. The test
compounds were nontoxic in the dose of 5 mg/kg body weight.
2
-1
1
25-127 °C; IR (KBr, νmax, cm ): 2927.14 (-CH
C=O, str), 1321.33 (C-N, str), 1433.24 (-CH , def), 1160.21
, δ ppm): 13.7 (s, 1H, -NH),
.33 (s, 5H), 7.21-7.18 (d, 2H, J = 15 Hz, Ar-H), 7.15 (s, 1H,
Ar-H), 6.8-6.78 (d, 2H, J = 10 Hz, Ar-H), 4.81 (s, 1H, CH-N),
3
, str), 1720.61
(
(
3
Antidiabetic activity
1
C-F, str); H NMR (DMSO-d
6
Oral glucose tolerance test on rat (OGTT): Twelve
groups of animals were administered normal saline at the dose
of 5 mg/kg for test compounds followed by administration of
glucose solution in the dose of 2g/kg.After 0.5 h of administration
of drug blood sample were withdrawn from dorsal vein at interval
7
13
3.43 (s, 1H, CH
2 2
-C=O); 3.15 (s, 1H, CH -C=O); C NMR
(DMSO-d , δ ppm): 170.3, 146.1, 143.3, 141.2, 133.5, 132.7,
6
1
1
31.3, 130.2, 130.2, 129.5, 129.5, 126.7, 124.7, 123.8, 123.8,
+
20.1, 108.3, 47.3, 47.3, 11.1; ESI-MS (m/e): 403.12 (M );
14
of 60, 120 and 180 min . Blood glucose level were estimated
using blood glucose test strip with elegance glucometer (Franken-
beng Germany) & GOD-POD kit (Acuurex, India).
Anal. (%) calcd. (found) for C20
H- 4 (3.81), N-10.42 (10.19).
16 3 3
H N OSF : C-59.54 (59.42),

6
620 Sen et al.
Asian J. Chem.
Induction of diabetes: Streptazocine (STZ) was used in
para and meta position of ring increases percentage yield
where as it decreases in case of ortho substitution due to steric
effect. Purification of compounds were done using hexane:
chloroform (2:8 v/v) for thiazolidine-4-ones by column
chromatography.
the dose of 60 mg/kg to induce insulin dependent diabetes.
streptazocine was injected into rats intraperitoneally. After 48
h of administration of streptazocine, the blood samples were
collected by dorsal vein for determination of blood glucose
15
level. The rat with fasting glucose level in range of 275-300
mg/100 mL - considered as diabetic and considered for study.
Experimental protocol and dose schedule: The total
periods for conductance of study were 21 days. The rats were
divided into 13 groups consisting of 06 animals in each group.
Group-1: Normal rats treated with normal saline 10
mL/kg p.o.
The formations of compounds were again confirmed by
elemental analysis (C, H, N analysis). In view of establishment
1
of structure spectral analysis has been performed by IR, H
13
NMR, C NMR and mass analysis. The IR peaks at 1775.51-
-
1
1701.61, 1685-1624, 1321.33-1260.33 and 1290-1200 cm
indicate presence of C=O, C=N, C-N groups in synthesized
1
compounds. The characteristic H NMR peaks at δ values 4.85-
Group-2: Diabetic control treated with streptazocine (60
mg/kg) dissolved in citrate buffer.
4.81, 3.49-3.43 and 3.25-3.15 ppm indicate presence of
thiazolidine-4-ones. The aromaticity of the compounds was
1
13
Group-3: Diabetic rat treated with rosiglitazone 8 mg/kg.
Group-4-13: Diabetic rat treated with test compounds at
mg/kg body weight.
also confirmed by H NMR. The C NMR spectral data also
describe characteristic peak according to proposed structure.
From the mass spectral analysis it was found that m/e peaks
according to calculated molecular mass of the synthesized
compounds.
5
On 1,7,14 and 21 days of study after 2 h of oral adminis-
tration of test compounds blood glucose levels and body weight
were measured. Blood samples were withdrawn through dorsal
vein. On 21 days whole blood was collected by cardiac puncture.
Blood sample collected then centrifuged at 3000 rpm for 10
min after to obtain serum. Blood glucose levels were estimated
by GOD-POD kit (Accurex. India).All biochemical parameters
Biological evaluation: in vitro Antioxidant activity was
determined by DPPH method. The DPPH assay method is
based on the reduction of DPPH, a stable free radical. The free
radical DPPH with an odd electron gives a maximum absor-
ption at 517 nm. When a solution of DPPH is mixed with that
of a substance that can donate a hydrogen atom, then this gives
16
were determined. Total cholesterol , triglyceride by Hantzsch
17
12
condensation method , serum urea and creatinine by method
rise to the reduced form with the loss of this violet colour . It
18
19
20
of Thomas , total protein , HDL cholesterol were measured.
Statistical analysis: The results were shown as Mean ±
SEM and comparison between standard and test compounds
were made by one way ANOVA followed by Dunnetts test.
Values of p ≤ 0.001 were considered as significant.
is well established that electron donating groups stabilize the
resulted phenoxyl radicals through inductive resonance effect;
thus lower the OH bond energy and enhance the radical scaven-
ging activity. In contrary, electron withdrawing groups stabilize
more the phenols and destabilize the resulted radicals. In
addition, a hydrogen bonding could be formed between the
phenoxyl unpaired electron and the adjacent hydroxyl group
that stabilizes the radicals formed more than it does for the
parent diols. Ascorbic acid is good antioxidant and exhibited
high activity reached 99.1 %. It could also undergo the two
hydrogen-atom transfer process to give the dehyroascorbic
acid. Due to this reason the compounds with electron donating
groups 7a, 7b, 7d, 7f, 7h had shown more IC50 values compare
to standard ascorbic acid. Whereas compounds with electron
withdrawing groups shown group have shown less IC50 value
compare to standard (Table-1).
RESULTS AND DISCUSSION
The present work involves cyclization of Schiff bases to
thiazolidine-4-ones derivatives. The Schiff bases (6a-6j) were
obtained by the reaction between electrophilic carbon atom
of substituted pyrazole-4-aldehyde and nucleophilic nitrogen
atom of substituted amines. The preparation of thiazolidine-
4
-ones (7a-7j) proceeds by an attack of sulphur nucleophile
of thioglycolic acid on imine carbon followed by intramole-
cular cyclization. During reaction one mole of water was
2 2
eliminated. SnCl , 2H O acted as acid catalyst which counters
balance between nucleophilicity and acidity for completion
of reaction. The substitution with electron donating group at
The acute toxicity study was performed. The study has
shown that at 5 mg/kg body weight the compounds are nontoxic.
TABLE-1
OBSERVATION FOR ANTIOXIDANT ACTIVITY IN TERMS OF DPPH METHOD
DPPH scavenging effect (%) [mean ± SEM]
Compound code
25 µg/mL
50 µg/mL
75 µg/mL
100 µg/mL
125 µg/mL
7
7
a
35.61 ± 0.060
38.06 ± 0.010
19.21 ± 0.120
32.39 ± 0.050
28.83 ± 0.098
37.26 ± 0.250
24.10 ± 0.130
15.00 ± 0.120
15.10 ± 0.170
28.44 ± 0.030
22.28 ± 0.120
51.31 ± 0.026
58.56 ± 0.060
21.37 ± 0.090
45.63 ± 0.025
34.95 ± 0.026
49.56 ± 0.130
32.12 ± 0.250
28.23 ± 0.010
20.11 ± 0.050
47.09 ± 0.120
41.03 ± 0.190
63.41 ± 0.098
73.91 ± 0.050
38.22 ± 0.240
57.24 ± 0.160
55.00 ± 0.023
60.40 ± 0.160
49.11 ± 0.120
35.31 ± 0.180
32.03 ± 0.200
51.89 ± 0.140
52.06 ± 0.200
76.97 ± 0.150
82.75 ± 0.120
43.44 ± 0.150
76.52 ± 0.052
69.24 ± 0.050
81.50 ± 0.090
52.97 ± 0.010
45.01 ± 0.080
45.80 ± 0.030
75.60 ± 0.210
75.02 ± 0.090
97.32 ± 0.026
96.20 ± 0.140
56.53 ± 0.160
93.70 ± 0.010
75.01 ± 0.110
97.47 ± 0.120
65.19 ± 0.110
52.11 ± 0.140
51.00 ± 0.080
96.48 ± 0.120
96.10 ± 0.180
b
7
c
7
d
7
e
7
f
7
7
g
h
7
i
7
j
STD (ascorbic acid)

Vol. 26, No. 19 (2014)
3-Phenylthiazolidin-4-ones Derivatives as Potent Antioxidant and Antidiabetic Agent 6621
The antidiabetic activity was performed by using streptozotocin
STZ) induced model in wister rat. Streptozotocin enters the
and potent agonists for the peroxisome proliferator activated
receptor (PPAR) γ that regulates the transcription of a number
of insulin responsive genes. Activation of PPAR-γ-receptors
regulates the transcription of insulin-responsive genes involved
in the control of glucose production, transport and utilization.
Additionally, PPAR-γ responsive genes also play a role in the
regulation of fatty acid metabolism. Unlike oral sulfonylureas,
rosiglitazone enhances tissue sensitivity to insulin rather than
(
pancreatic cell via a glucose transporter GLUT2 and causes
alkylation of deoxyribonucleic acid. Streptozotocin induces
activation of poly adenosine ribosylation and nitric oxide
release. Due to destruction of pancreatic cells by streptazocine
a huge release of insulin which makes animals more susceptible
to severe hypoglycemia that may be lethal. Due to this reason
animal treated with streptazocine were administered with 5 %
glucose solution for 12-24 h.Afterwards, an increase of glucose
levels was observed in comparison to control animals due to
2
1
stimulates insulin secretion . Blood glucose levels in rats
administered with 2 g/kg glucose were significantly decreased
by test compounds with in 1 h as compared to standard group.
Treatment with compounds 7a-7j has shown that there are
significant fall of blood glucose level compared to standard
rosiglitazone on 21 day of study. But on 21 day of treatment it
15
insulin deficiency (Table-2) . The thiazolidine were dependent
on the presence of insulin for activity. However, they do not
affect insulin secretion. The thiazolidine were highly selective
TABLE-2
ANTIDIABETIC ACTIVITY LONG TERM EFFECT OF STANDARD (8 MG/KG BODY wt.)
AND COMPOUNDS (5 mg/kg BODY wt.) ON BLOOD GLUCOSE LEVEL OF RAT
Compound No.
0 min
60 min
120 min
180 min
OGTT blood glucose level (mg/dl)
106.2 ± 3.02
110.0 ± 3.94
152.2 ± 7.34
126.3 ± 1.23
182.7 ± 1.5
Control
91.5 ± 2.23
91.5 ± 2.23
93.83 ± 0.6
91.2 ± 2.21
93.83 ± 0.6
92.2 ± 1.21
90.5 ± 2.11
91.2 ± 2.21
91.2 ± 2.21
96.33 ± 0.98
96.33 ± 0.98
92.62 ± 0.87
0 days
103 ± 7
108 ± 1.89
132 ± 0.85
115 ± 2.6
93.67 ± 1.00
97.83 ± 0.47***
90.83 ± 0.47***
93.5 ± 2.46***
93.5 ± 2.46
Rosiglitazone
7a
7b
7c
143.3 ± 3.12
113.2 ± 2.3
110.1 ± 1.6
114.2 ± 2.6
115.3 ± 2.6
149.2 ± 2.38
149.2 ± 2.38
130 ± 2.4
7d
120.1 ± 1.23
126.3 ± 1.23
126.3 ± 1.23
126.3 ± 1.23
191.8 ± 4.7
96.5 ± 2.46**
93.5 ± 2.46**
93.5 ± 2.46
7e
7f
7g
110.5 ± 2.46**
95 ± 1.82***
96.12 ± 1.82**
94.3 ± 2.12***
21 days
7h
7i
191.8 ± 4.7
7j
153.2 ± 1.23
7 days
Compound No.
14 days
Fasting blood glucose level (mg/dl)
115.7 ± 3.9
Control
91 ± 1.00
244.7 ± 2.96
311.3 ± 3.99
301.7 ± 3.07
285 ± 4.8
114 ± 6.8
311 ± 3.99
100 ± 2.47
336 ± 2.12
Diabetic control
Rosiglitazone
281.3 ± 2.51
247.8 ± 7.4
126.7 ± 5.8
132.2 ± 1.65
124.5 ± 1.60
119.5 ± 1.04
116.5 ± 1.04
115.5 ± 1.04
114.5 ± 1.04
113.5 ± 1.04
124.5 ± 1.29
121.5 ± 1.29
120 ± 1.89
106.5 ± 1.9
7a
152.5 ± 1.2
97.83 ± 0.87***
95.33 ± 1.33***
112.12 ± 2.26
105.12 ± 2.26**
103.12 ± 2.26**
101.12 ± 2.26**
105.32 ± 2.26
87 ± 3.48***
104 ± 3.48**
96.11 ± 2.26***
7b
136.7 ± 2.04
123.2 ± 0.94
120.1 ± 0.84
113.2 ± 0.93
125.1 ± 0.92
124.2 ± 0.91
132.8 ± 3.19
142.8 ± 3.19
193 ± 3.73
7c
301.7 ± 3.07
311.7 ± 3.07
281.7 ± 3.07
2911.7 ± 3.07
312.7 ± 3.07
250.3 ± 8.51
253.3 ± 8.51
286.5 ± 1.19
7d
7e
7f
7g
7h
7i
7j
Change in bodyweight (gm)
169 ± 0.5
Control
160 ± 0.6
178.5 ± 0.99
171 ± 0.39
168 ± 0.51
169 ± 0.66
165 ± 0.6
163 ± 0.6
162 ± 0.4
164 ± 0.3
167 ± 0.2
170 ± 0.21
169 ± 0.21
168 ± 0.4
166 ± 0.8
215 ± 0.56
141 ± 0.60
137 ± 0.4
142 ± 0.7
143 ± 0.46
157 ± 0.41
153 ± 0.46
153 ± 0.46
153 ± 0.46
155 ± 0.3
153 ± 0.3
141 ± 0.52
163 ± 0.2
253 ± 0.12
Diabetic control
Rosiglitazone
190 ± 0.69
144.5 ± 0.67
141 ± 0.6
169 ± 0.6
7a
162 ± 0.3***
156 ± 0.2***
148 ± 0.2
7b
132 ± 0.25
7c
158 ± 0.7
7d
148 ± 0.7
159 ± 0.2**
161 ± 0.2**
159.1 ± 0.2**
165 ± 0.2
7e
138 ± 0.7
7f
157 ± 0.7
7g
154 ± 0.7
7h
161 ± 0.4
168 ± 0.2***
168 ± 0.2**
159 ± 0.67***
7i
161 ± 0.4
7j
123 ± 0.61
***
**
Data analyzed by one-way ANOVA followed by Dunnett’s test (n = 6). P ≤ 0.001 were considered as significant. P ≤ 0.05 were considered as
moderate in activity

6
622 Sen et al.
Asian J. Chem.
TABLE-3
BIOCHEMICAL PARAMETER OF RAT
Compound No. group
(
Cholesterol
(mg/dl)
Triglycerides
HDL
Cholesterol (mg/dl)
34.1 ± 1.8
Total
Creatinin (mg/dl)
Urea (mg/dl)
mg/kg body wt.)
(mg/dl)
83.3 ± 4.6
Protein (g/dl)
8.3 ± 1.7
Control
148 ± 1.5
290 ± 1.9
0.6 ± 0.4
2 ± 1.9
22 ± 0.4
Diabetic control
Rosiglitazone(8)
258 ± 9.8
80 ± 3.2
28 ± 1.8
4 ± 3.2
119 ± 2.8
101 ± 5.2
0.41 ± 1
32.2 ± 3.1
63 ± 2.9
8.4 ± 0.4
7
a (5)
b (5)
136.8 ± 0.7***
144.5 ± 0.8***
143.8 ± 1.2
137 ± 1***
138 ± 1***
123 ± 1.11
123 ± 1.11**
111.1 ± 1.11**
133.2 ± 1.11**
123 ± 1.11
0.77 ± 0.1***
0.47 ± 0.01***
0.63 ± 0.01
25.67 ± 0.61***
23.67 ± 0.42***
24.17 ± 1.02
32.33 ± 2.41***
36.17 ± 0.94***
38.5 ± 2.34
7.7 ± 0.8***
7.6 ± 0.3***
7.2 ± 0.1
7
7
c (5)
7d (5)
156.8 ± 1.1**
190.7 ± 1.3**
142.8 ± 1.2**
173.8 ± 1.2
0.53 ± 0.01**
0.50 ± 0.01**
0.65 ± 0.01**
0.73 ± 0.01
29.17 ± 1.02**
34.17 ± 1.02**
33.17 ± 1.02**
54.17 ± 1.02
58.5 ± 2.34**
48.5 ± 2.34**
48.5 ± 2.34**
42.5 ± 2.34
5.8 ± 0.1**
4.2 ± 0.1**
5.7 ± 0.1**
3.2 ± 0.1
7
e(5)
7
f (5)
7
g (5)
h (5)
7
149.8 ± 1.19*** 125.5 ± 1.6***
0.56 ± 0.06***
0.61 ± 0.03**
0.55 ± 0.08***
26.17 ± 0.03***
29.17 ± 0.02**
23.17 ± 0.7***
33.83 ± 1.53***
43.83 ± 1.53**
6.9 ± 0.1***
5.3 ± 0.1**
7.0 ± 1.3***
7
i (5)
141.1 ± 1.7**
131.23 ± 1.3**
152 ± 2.5***
7
j (5)
150.5 ± 2.23***
30.86 ± 3.10***
**
***
Data analyzed by one-way ANOVA followed by Dunnett’s test (n = 6). P ≤ 0.001 were considered as significant. P ≤ 0.05 were considered as
moderate in activity
was found that there is significant gain of body weight specially
the rat treated with test compound. There was decrease in serum
cholesterol, triglyceride, creatinine, urea levels are decreased
significantly where as the HDL level and total protein levels
are found to increase after 21 days treatment. But out of all
the compounds tested 7a, 7b, 7h, 7j shown more significant
antidiabetic effect against hyperglycemic rats but there is no
significant effect found in case of normoglycemic condition.
Whereas compounds 7d, 7e, 7f, 7g, 7i have shown modeate
activity and compounds 7c, 7g were not significant (Table-3).
From the SAR study it was confirmed that presence of
thiazolidine-4-one nucleus along with pyrazole nucleus is
essential for both antioxidant and antidiabetic activity. But
overall effect depends upon substitution on phenyl ring attached
to thiazolidine nucleus. Compounds with para substitution are
potent, where as compound with para and meta substitution
shown moderate activity. The ortho substituted compounds
are not potent. It were also confirmed that electron withdrawing
substituents at para or meta position decrease the potency of
compounds.
Lab, New Delhi. The authors also wish to acknowledge
Arunabaha Mallik, Assistant Professor, Bansal College of
Pharmacy, Bhopal for providing the facility for animal study.
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The authors acknowledge to IIMT College of Medical
Sciences; Regional Institute of Pharmaceutical sciences and
Technology, Govt of Tripura;AIRF, JNU, New Delhi andArbro
9