Synthesis and biological evaluation of pyrazolylthiazole carboxylic acids as potent anti-inflammatory-antimicrobial agents

Article abstract of DOI:10.1016/j.bmcl.2015.02.004

Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R = Cl, R¹ = Cl), 2c (R = H, R¹ = F) and 2n (R = Cl, R¹ = OCH₃) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59which is comparable to the reference drug indomethacin (91.32%) after 3 h of carrageenan injection while most of the other compounds displayed inhibition ≥80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R = OCH₃, R¹ = Cl) showed excellent antimicrobial activity (MIC 6.25 μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25 μg/mL).

Full text of DOI:10.1016/j.bmcl.2015.02.004

Bioorganic & Medicinal Chemistry Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Synthesis and biological evaluation of pyrazolylthiazole carboxylic
acids as potent anti-inflammatory–antimicrobial agents
Poonam Khloya a, Satish Kumar a, Pawan Kaushik b, Parveen Surain c, Dhirender Kaushik b,
Pawan K. Sharma a,
⇑
a Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India
b Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119, India
c Department of Microbiology, Kurukshetra University, Kurukshetra 136119, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole
carboxylates 1a–1p and corresponding acid derivatives 2a–2p. All 32 novel compounds were tested for
their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for
in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three
compounds 1p (R = Cl, R1 = Cl), 2c (R = H, R1 = F) and 2n (R = Cl, R1 = OCH3) were identified as potent
anti-inflammatory agents exhibiting edema inhibition of 93.06–89.59% which is comparable to the refer-
ence drug indomethacin (91.32%) after 3 h of carrageenan injection while most of the other compounds
displayed inhibition P80%. In addition, pyrazolylthiazole carboxylic acids (2a–2p) also showed good
antimicrobial profile. Compound 2h (R = OCH3, R1 = Cl) showed excellent antimicrobial activity (MIC
Received 16 August 2014
Revised 23 January 2015
Accepted 4 February 2015
Available online xxxx
Keywords:
Pyrazole
Thiazole
Anti-inflammatory activity
Antimicrobial activity
6.25
lg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin
(MIC 6.25
lg/mL).
Ó 2015 Elsevier Ltd. All rights reserved.
Inflammation is the immune response of tissues to external
injury which can be categorized as acute or chronic. The former
is the initial response of the body to harmful stimulus identified
by the increased movement of macrophages and neutrophils in
infected tissues while chronic inflammation is due to progressive
movement of the mononucleated cells at the injury site leading
to destruction of tissues by cell death.1
Anti-inflammatory drugs are known to inhibit one or more
isoforms of cyclooxygenase (COX) enzyme that catalyzes the con-
version of arachidonic acid (AA) into prostaglandins (PGs) and
thromboxanes. COX enzyme is a rate-limiting enzyme that exists
in two isoforms; constitutive (COX-1) and inducible (COX-2). COX-
1 is believed to be a housekeeping enzyme constitutively present
in platelets and all tissues. It produces PGs involved in important
physiological functions, such as gastric mucosal cytoprotection,
renal homeostasis, and platelet aggregation. COX-2 is an inducible,
short lived enzyme present in brain, kidney and endothelial cells
and facilitates the release of PGs in the inflammatory process.2–4
Conventional non-steroidal anti-inflammatory drugs (NSAIDs)
like aspirin and ibuprofen are nonselective inhibitors of both
the isoforms of COX thereby leading to a number of renal and
gastrointestinal (GI) side effects.5 To overcome the gastrointestinal
side effects, selective COX-2 inhibitors such as celecoxib,6 rimona-
bant,7 valdecoxib,8 rofecoxib,9 deracoxib10 etc., which block the
production of PGs in inflammatory cells,11 have been developed
since 1999. Success of these ‘coxibs’ led to an increased attention
towards development of more candidates like the approved COX-
2 selective inhibitors which are typical models of the diarylhetero-
cycles template.12
Resistance of microbes to existing antimicrobial drugs is a cause of
serious concern. Considering the obvious advantages of mono-
therapy against inflammation as well as microbial infection, research
efforts are underway to develop dual anti-inflammatory–antimicro-
bial drugs with minimum GI side effects and high safety margin.13
Thiazole14–17 and pyrazole nuclei18–23 are ubiquitous motifs rep-
resenting an interesting array of heterocyclic compounds exhibiting
a wide range of biological activities such as antimicrobial, anti-
inflammatory, antitubercular, anticonvulsant, antitumor etc. Moti-
vated by these findings, and in continuation of our ongoing research
program in the field of 4-functionalized pyrazole analogues24–27 and
other biologically active heterocyclic compounds28–34 we present in
this Letter, design, synthesis and evaluation of pyrazolylthiazole
carboxylic acids (2a–2p) and their ester analogues (1a–1p) as
dual anti-inflammatory–antimicrobial agents (Fig. 1). Thiazole ring
possessing carboxylic group have been incorporated at N-1 position
⇑
Corresponding author. Tel.: +91 9416457355; fax: +91 1744 238277.
E-mail address: pksharma@kuk.ac.in (P.K. Sharma).
http://dx.doi.org/10.1016/j.bmcl.2015.02.004
0960-894X/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Khloya, P.; et al. Bioorg. Med. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.bmcl.2015.02.004

2
P. Khloya et al. / Bioorg. Med. Chem. Lett. xxx (2015) xxx–xxx
Functionalization at
4-position of pyrazole
4-carbothioamidepyrazoles (10), which were prepared by multi-
step synthesis.
R1
R1
Ethyl 3-aryl-3-oxopropanoates 5 were prepared by the base
catalyzed carbethoxylation of the appropriately substituted
acetophenones 3 with diethyl carbonate 4. Bromination of 5 was
achieved by grinding ethyl 3-aryl-3-oxopropanoates 5 with NBS36
without solvent leading to the exclusive formation of monobromi-
nated pure products 6 in excellent yield. 4-Carbothioamidepyrazoles
10 were synthesized starting from appropriate acetophenones using
a multistep strategy involving hydrazone synthesis, Vilsmeier–
Haack reaction followed by oxidative amination and subsequent
thiolysis of 4-cyanopyrazoles 9 by using H2S gas under basic condi-
tions in the presence of triethylamine as reported recently by our
group.25 The target compounds pyrazolylthiazole carboxylates
1a–1p were synthesized by the condensation of appropriate 4-carbo-
thioamidepyrazoles 10 with substituted ethyl 2-bromo-3-aryl-
3-oxopropanoates (6) in the presence of catalytic amount of glacial
acetic acid in refluxing ethanol for 5–6 h. Pyrazolylthiazole carboxyl-
ates 1a–1p were converted into corresponding pyrazolylthiazole
carboxylic acids 2a–2p following basic hydrolysis of the ester group
using sodium hydroxide (NaOH) solution under reflux for 3–4 h in
good yield.
O
O
O
OH
N
N
N
N
S
S
R2
R2
N
N
1a-1p
2a-2p
Figure 1. Pyrazolylthiazole carboxylates 1a–1p and corresponding carboxylic acids
2a–2p.
of pyrazole ring35 in the past but here in this Letter, to the best of our
knowledge, we have introduced the thiazolecarboxylic acid func-
tionality at 4-position of pyrazole ring (1a–1p and 2a–2p) for the
first time (Fig. 1).
The synthetic strategy adopted for the synthesis of the target
compounds is depicted in Scheme 1. The basic requirements for
the synthesis of pyrazolylthiazole carboxylic acids (2) were the
formation of ethyl 2-bromo-3-aryl-3-oxopropanoates (6) and
The newly synthesized target compounds (1a–1p and 2a–2p)
were characterized by rigorous analysis of their IR, 1H NMR, 13C
NMR and mass spectral data. IR spectra of pyrazolylthiazole
Br
O
O
O
O
O
O
OC2H5
OC2H5
(a)
(b)
+
C2H5O
OC2H5
R1
R1
R1
3
4
5
6
O
NHNH2
N
N
N
N
+
(g)
(f)
(c, d, e)
reference 19
R2
R2
R2
CN
S
NH2
7
8
9
10
N
N
N
N
R2
(h)
R2
N
S
N
S
OH
OCH2CH3
O
O
R1
R1
1
2
Comp No.
1, 2
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
R1
R2
H OCH3
F
Cl
H
H
OCH3
F
Cl
H
F
OCH3
F
F
F
Cl
F
H
OCH3
Cl
F
Cl
H
H
H
OCH3 OCH3 OCH3 OCH3
Cl
Cl Cl
Scheme 1. Reagents and conditions: (a) NaH, benzene, diethyl carbonate reflux; (b) NBS, grinding; (c) ethanol–water, reflux; (d) POCl3/DMF, 50–60 °C, 6 h; (e) I2/NH3, THF stir
overnight; (f) H2S, NEt3, pyridine, 10–12 h; (g) ethyl 2-bromo-3-aryl-3-oxopropanoate 6, ethanol, 1–2 drops of glacial acetic acid, reflux; (h) NaOH/H2O/C2H5OH, reflux.
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P. Khloya et al. / Bioorg. Med. Chem. Lett. xxx (2015) xxx–xxx
3
Table 1
In vivo anti-inflammatory (AI) activity of compounds (1a–1p and 2a–2p) in carrageenan induced rat paw edema assay (acute inflammatory model)
Compounds
Volume of edemaa (mL) and % AIb
1h
2h
3h
4h
Swelling
Inhibition (%)
Swelling
Inhibition (%)
Swelling
Inhibition (%)
Swelling
Inhibition (%)
Control
Indomethacin
1.11 0.12
0.07 0.02*
0.10 0.02*
0.22 0.08*
0.29 0.08*
0.22 0.06*
0.11 0.03*
0.15 0.06*
0.18 0.04*
0.15 0.04*
0.26 0.10*
0.22 0.08*
0.16 0.08*
0.17 0.04*
0.12 0.04*
0.10 0.03*
0.18 0.08*
0.18 0.08*
0.24 0.07*
0.19 0.06*
0.19 0.06*
0.14 0.02*
0.20 0.10*
0.13 0.04*
0.19 0.03*
0.18 0.06*
0.14 0.02*
0.22 0.05*
0.23 0.05*
0.33 0.03*
0.32 0.07*
0.15 0.04*
0.29 0.09*
0.26 0.05*
1.21 0.16
0.14 0.05*
0.30 0.06*
0.29 0.08*
0.22 0.09*
0.15 0.11*
0.20 0.01*
0.19 0.14*
0.18 0.06*
0.38 0.11*
0.32 0.10*
0.27 0.07*
0.25 0.05*
0.22 0.03*
0.22 0.03*
0.35 0.06*
0.47 0.11*
0.27 0.08*
0.39 0.10*
0.25 0.07*
0.16 0.04*
0.21 0.05*
0.16 0.04*
0.24 0.11*
0.22 0.07*
0.26 0.05*
0.22 0.05*
0.40 0.07*
0.57 0.22*
0.64 0.16*
0.46 0.11*
0.19 0.04*
0.33 0.10*
0.23 0.06*
1.73 0.09
0.15 0.03*
0.28 0.06*
0.24 0.10*
0.31 0.06*
0.24 0.12*
0.33 0.08*
0.27 0.11*
0.31 0.13*
0.38 0.11*
0.33 0.02*
0.39 0.07*
0.32 0.06*
0.34 0.11*
0.32 0.07*
0.25 0.08*
0.50 0.13*
0.12 0.04*
0.28 0.06*
0.24 0.05*
0.18 0.04*
0.20 0.06*
0.21 0.09*
0.20 0.06*
0.31 0.17*
0.28 0.05*
0.37 0.09*
0.56 0.14*
0.61 0.12*
0.75 0.14*
0.69 0.19*
0.16 0.05*
0.49 0.10*
0.43 0.08*
1.88 0.20
0.16 0.05*
0.24 0.06*
0.34 0.14*
0.42 0.13*
0.22 0.10*
0.24 0.08*
0.17 0.04*
0.37 0.06*
0.53 0.08*
0.45 0.09*
0.32 0.09*
0.23 0.05*
0.26 0.07*
0.28 0.10*
0.21 0.07*
0.19 0.04*
0.18 0.07*
0.30 0.01*
0.22 0.07*
0.17 0.03*
0.22 0.05*
0.23 0.08*
0.19 0.06*
0.18 0.04*
0.20 0.07*
0.18 0.04*
0.36 0.10*
0.47 0.13*
0.37 0.11*
0.54.0.11*
93.69
90.99
80.18
73.87
80.18
90.19
86.48
83.78
86.48
76.57
80.18
85.58
84.68
89.89
90.99
83.78
83.78
87.37
82.88
82.88
87.38
81.98
82.88
82.88
83.78
87.38
80.18
79.27
70.27
71.17
86.48
73.87
76.57
88.42
75.20
76.03
81.81
87.60
83.47
84.29
85.12
68.59
73.55
79.33
79.33
81.81
81.81
71.07
61.15
77.68
67.76
79.33
86.77
82.64
86.77
86.77
81.81
78.51
81.81
66.94
52.89
47.10
61.98
89.29
72.72
80.99
91.32
83.81
86.12
82.08
87.23
80.92
84.39
82.08
78.03
80.92
77.45
81.50
80.34
81.50
85.54
71.09
93.06
83.81
86.12
89.59
88.43
87.86
88.43
82.08
83.81
78.61
67.63
64.73
56.14
60.11
90.75
71.67
75.14
91.48
87.23
81.91
88.29
87.23
90.95
90.95
80.31
71.80
76.06
82.97
87.76
86.17
85.10
88.92
89.89
90.42
84.04
88.29
90.95
88.29
87.76
89.89
90.42
89.36
90.42
80.85
75.00
80.31
71.27
88.82
79.78
85.10
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
0.21 0.03*
0.38 0.10*
0.28 0.08*
*
a
b
Significantly different compared to respective control values, P <0.01.
Values are expressed as mean SEM (number of animals = 6) and analyzed by ANOVA.
Values in parentheses (percentage anti-inflammatory activity, AI %).
carboxylates (1a–1p) displayed a characteristic C@O stretch of
ester moiety around 1713 cmÀ1 and their 1H NMR spectra exhib-
ited a typical triplet–quartet pattern; a quartet around d 4.30–
4.01 and a triplet around d 1.30–1.01 which could be assigned to
the ethoxy group of ester moiety present at C-5 position of thiazole
ring. The final pyrazolylthiazole carboxylic acids 2a–2p exhibited
carbonyl absorption band (C@O) around 1674–1682 cmÀ1 in their
IR spectra. The disappearance of signals corresponding to the eth-
oxy group and appearance of a broad singlet due to carboxylic
group in their 1H NMR spectra confirmed the conversion of carbox-
ylates into corresponding pyrazolylthiazole carboxylic acids. The
other protons appeared in the aromatic region in full agreement
with the proposed structures. The mass spectra of all the synthe-
sized compounds showed molecular ion peak at M+1 correspond-
ing to their molecular formula further substantiating the chemical
structures.
The 32 newly synthesized compounds 1a–1p and 2a–2p were
evaluated for their in vivo anti-inflammatory activity by carra-
geenan-induced rat paw edema method. The protocol of animal
experiments has been approved by the Institutional Animal Ethics
Committee (IAEC). Each test compound was dosed orally (50 mg/
kg body weight) 30 min prior to induction of inflammation by
carrageenan injection. Indomethacin was used as a reference
anti-inflammatory drug and anti-inflammatory activity was calcu-
lated at hourly intervals up to 4 h after injection and presented in
Table 1 as the mean paw volume (mL) as well as the percentage
anti-inflammatory activity (% AI). Considering the fact that carra-
geenan-induced paw edema assay is a biphasic event involving
120
80
40
0
3h
4h
i
a
c
e
1
k
1
g
o
1
m
in
1
1
1
1
1
c
a
h
t
e
m
o
d
n
I
Compounds/Standard Drug
Figure 2. Comparison of Al activity of newly synthesized compounds (1a–1p) and
standard drug indomethacin after 3 h and 4 h carrageenan injection.
the release of histamine and serotonin as the mediators of inflam-
mation in the first phase which normally lasts for about 2 h after
the carrageenan injection followed by the second phase which
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P. Khloya et al. / Bioorg. Med. Chem. Lett. xxx (2015) xxx–xxx
120
80
40
0
biphasic event can be attributed to the inhibition of prostaglandin
synthesis. A careful study of the results shown in Table 1 revealed
that most of the compounds showed significant AI activity 3 h and
4 h after carrageenan injection with as many as 22 compounds
showing more than 80% inhibition after 3 h (as compared to the
reference drug 91.32%) and 26 compounds showing more than
80% inhibition after 4 h (as compared to the references drug
91.48%). Three compounds out of all the tested compounds, 1p
(R = Cl, R1 = Cl), 2c (R = H, R1 = F) and 2n (R = Cl, R1 = OCH3) showed
remarkable AI activity ranging from 93.06% to 89.59% comparable
to the reference drug indomethacin (91.32%) 3 h after carrageenan
injection. Eight other compounds 1b, 1d, 1n and 2b–2f showed
appreciable AI activity ranging from 89.59% to 85.54% 3 h after car-
rageenan injection. Twelve compounds 1a, 1c, 1e–1g, 1i, 1k–1m,
2a, 2g and 2h, exhibited AI activity 84.39–80.34% inhibition while
remaining compounds in the two series displayed AI activity P60%
3 h after carrageenan injection. After 4 h of carrageenan injection,
nine compounds 1e–1f, 1o–1p, 2c, 2f–2g, 2i and 2h showed AI
activity ranging from 90.95% to 89.36% inhibition comparable to
indomethacin (91.48%). Seventeen other compounds, 1a–1b, 1d,
1g, 1j, 1k–1n, 2a–2b, 2d, 2e, 2j, 2l, 2n and 2p showed AI activity
P80% while remaining five compounds exhibited AI activity
P71% inhibition 4 h after carrageenan injection. Graphical com-
parison of AI activity of newly synthesized compounds (1a–1p
and 2a–2p) with standard drug indomethacin after 3 h and 4 h
carrageenan injection is shown in Figures. 2 and 3.
3h
4h
Compounds/Standard Drug
Figure 3. Comparison of Al activity of newly synthesized compounds (2a–2p) and
standard drug indomethacin after 3 h and 4 h carrageenan injection.
generally operates between 2 h and 4 h after the carrageenan
injection and involves prostaglandins as the mediators for the
inflammation, thus any AI activity in the second phase of this
Careful study of the results presented in the Table 1 revealed
excellent AI profile of all the newly synthesized compounds 1
Table 2
In vitro antimicrobial activity and MIC of compounds 1a–1p and 2a–2p using agar well diffusion method
Compoundsa
Diameter of growth of inhibition zone in mmb (MIC
l
g/mL)c
Saccharomyces cerevisiae
Staphylococcus aureus
Bacillus subtilis
Escherichia coli
Pseudomonas aeruginosa
Candida albicans
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
14.3 (50)
—
—
—
11.0 (50)
13.6 (50)
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
25.0
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
22.0
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
15.3 (50)
16.3 (50)
18.6 (25)
17.3 (50)
18.3 (25)
16.6 (50)
24.6 (12.5)
14.3 (50)
16.6 (50)
15.6 (50)
22.6 (12.5)
17.6 (50)
16.0 (50)
15.3 (50)
17.6 (50)
13.0 (50)
17.6 (50)
15.3 (50)
25.6 (12.5)
17.6 (50)
16.3 (50)
13.0 (50)
12.0 (50)
27.6 (6.25)
21.3 (25)
15.3 (50)
19.6 (25)
20.6 (25)
24.6 (12.5)
25.3 (12.5)
12.0 (50)
23.6 (12.5)
—
—
15.0 (50)
—
20.6 (25)
14.3 (50)
—
13.3 (50)
15.6 (50)
—
12.0 (50)
15.3 (50)
13.3 (50)
—
18.6 (25)
17.6 (50)
18.3 (25)
17.6 (50)
18.6 (25)
16.3 (50)
12.0 (50)
29.6 (6.25)
18.3 (25)
14.6 (50)
17.6 (50)
18.3 (25)
22.6 (12.5)
18.3 (25)
—
15.0 (50)
—
—
—
—
—
—
—
—
12.0 (50)
—
15.0 (50)
23.6 (12.5)
21.3 (25)
20.6 (25)
20.6 (25)
16.0 (50)
13.3 (50)
15.3 (50)
27.6 (6.25)
15.6 (50)
15.3 (50)
17.6 (25)
20.6 (25)
26.6 (12.5)
12.0 (50)
24.6 (12.5)
24.6 (12.5)
24.6 (12.5)
20.3 (25)
24.6 (12.5)
21.0 (25)
21.6 (25)
16.3 (50)
12.0 (50)
24.6 (12.5)
20.3 (25)
20.6 (25)
15.3 (50)
21.6 (25)
22.6 (25)
—
—
—
16.6 (50)
24.0 (6.25)
Ciprofloxacin
Amphoterician B
24.0 (6.25)
19.3 (6.25)
16.6 (6.25)
—No activity.
a
Concentration 4.0 mg/mL.
b
c
Values, including diameter of the well (8 mm), are means of three replicates.
MIC ( g/mL) = minimum inhibitory concentration.
l
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P. Khloya et al. / Bioorg. Med. Chem. Lett. xxx (2015) xxx–xxx
5
and 2 implying that the pyrazolylthiazole carboxylates or carbox-
ylic acids represent an excellent scaffold for designing antiinflam-
matory agents. It can be claimed, based on the data presented in
Table 1, that AI activity of the ester derivatives, in general, was
found to be superior to the acids. It is difficult to draw a correlation
between the AI activity and the substituents present on the aro-
matic rings in 1 or 2 as the AI activity seems to be independent
of the nature of substituents. The excellent AI inhibition exhibited
by these compounds, 4 h after carrageenan injection suggested
that these compounds do not get easily metabolized in the body.
Additionally, all the 32 newly synthesized compounds 1a–1p
and 2a–2p were also screened for their in vitro antimicrobial activ-
ity against four pathogenic bacteria Bacillus subtilis (MTCC 121),
and Staphylococcus aureus (MTCC 96) representing Gram-positive
bacteria, Pseudomonas aeruginosa (MTCC 741) and Escherichia coli
(MTCC 1652) representing Gram-negative bacteria (Table 2) and
two pathogenic fungal strains Candida albicans (MTCC 3017) and
Saccharomyces cerevisiae (MTCC 170) by agar well diffusion method
using ciprofloxacin and fluconazole as the reference drugs. The
Minimum Inhibitory Concentration (MIC) measurements were
performed using a macrodilution method (Table 2).
(Haryana), India for the award of Senior Research Fellowships.
The authors are thankful to Sophisticated Analytical Instrument
Facility, Central Drug Research Institute, Lucknow for providing
Mass spectra.
Supplementary data
Supplementary data (biological assay, experimental procedure
and spectroscopic characterization of compounds 1a–1p and
2a–2p) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.bmcl.2015.02.004.
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In conclusion, synthesis of pyrazolylthiazole carboxylates and
their corresponding acids was achieved in good yield and the same
were evaluated for their in vivo anti-inflammatory activity as well
as for in vitro antimicrobial activity. Compounds 1p (R = Cl, R1 = Cl),
2c (R = H, R1 = F) and 2n (R = Cl, R1 = OCH3) showed significant AI
activity ranging from 93.06% to 89.59% comparable to the reference
drug indomethacin 3 h after carrageenan injection while 4 h after
carrageenan injection, nine compounds 1e–1f, 1o–1p, 2c, 2f–2g,
2i and 2h showed AI activity ranging from 90.95% to 89.36%
inhibition comparable to indomethacin (91.48%). In case of antimi-
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Acknowledgements
One of the authors (Poonam Khloya) is grateful to the Haryana
State Council for Science and Technology (HSCST), Panchkula
Please cite this article in press as: Khloya, P.; et al. Bioorg. Med. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.bmcl.2015.02.004