Synthesis and antimicrobial activities of some new 5-((3-(aryl)-1-phenyl- 1H-pyrazol-4-yl)methylene)-3-phenylthiazolidine-2,4-diones

Article abstract of DOI:10.1007/s00044-010-9503-2

Aseries of nine newcompounds of 5-((3-(aryl)-1- phenyl-1H-pyrazol-4-yl) methylene)-3-phenylthiazolidine- 2,4-diones was synthesized by Knoevenagel condensation of various 3-(aryl)-1-phenyl-1H-pyrazole-4-carbaldehydes with 3-phenylthiazolidine-2,4-dione in

Full text of DOI:10.1007/s00044-010-9503-2

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:10–15
DOI 10.1007/s00044-010-9503-2
ORIGINAL RESEARCH
Synthesis and antimicrobial activities of some new 5-((3-(aryl)-1-
phenyl-1H-pyrazol-4-yl)methylene)-3-phenylthiazolidine-2,4-
diones
•
Om Prakash Deepak Kumar Aneja
•
•
Sanjiv Arora Chetan Sharma K. R. Aneja
•
Received: 27 January 2010 / Accepted: 3 November 2010 / Published online: 17 November 2010
Ó Springer Science+Business Media, LLC 2010
Abstract Aseriesofninenewcompoundsof5-((3-(aryl)-1-
phenyl-1H-pyrazol-4-yl)methylene)-3-phenylthiazolidine-
2,4-diones was synthesized by Knoevenagel condensation
of various 3-(aryl)-1-phenyl-1H-pyrazole-4-carbaldehydes
with 3-phenylthiazolidine-2,4-dione in ethanol in the
presence of piperidine as a catalyst. The reaction afforded
the desired products in good yields. All the nine compounds
were screened for their in vitro antibacterial (Staphylo-
coccus aureus, Bacillus subtilis, Pseudomonas aeruginosa
and Escherichia coli) and antifungal (Aspergillus niger and
A. flavus) activity. Biological activities of these compounds
were compared with those of commercially available anti-
biotics, ciprofloxacin and antifungal agent fluconazole.
Two compounds 3e and 3i were found to be most effective
against S. aureus and B. subtilis. Out of the nine compounds
tested for antifungal activity, five, 3c–f and 3h showed more
than 50% inhibition against the A. flavus, whereas the three
compounds 3a, 3d and 3f showed more than 50% inhibition
against A. niger.
Introduction
Over the years, 4-thiazolidinones have enjoyed a prominent
place in heterocyclic chemistry largely due to the wide range
of biological activity associated with this class of com-
pounds (Bhargava and Chaurasia, 1969). Diverse biological
activities, namely, antihyperglycemic (Lee et al., 2005),
bactericidal (Mahalle et al., 2008; Bozdag-Dundar et al.,
2008a, b), pesticidal (Hyo et al., 2007), fungicidal (Deohate
et al., 2004), insecticidal (Sahu et al., 2007), anticonvulsant
(Altintas et al., 2006), tuberculostatic (Thaker et al., 2003),
anti-inflammatory (Szeto and Li, 2008; Pastromas et al.,
2008; Murugan et al., 2009; Cioni and Ramelli, 2009; Sha
et al., 2009), antithyroid and potentiation of pentobarbital
induced sleeping time, etc., have been associated with
thiazolidinone derivatives. Different possibilities of het-
erocyclic modifications (Bozdag-Dundar et al., 2008a, b)
with a wide spectrum of pharmacological properties are the
most important grounds for investigation of this class of
compounds (Jeon et al., 2006; Chandrappa et al., 2008;
Ramesh et al., 2004; Clark et al., 1991; Tuncbilek and
Altanlar, 1999, 2006). The fifth position of thiazolidine-2,
4-diones (the active methylene group) being relatively more
reactive, hence most of the modification at this position
exhibit a wide spectrum of pharmacological properties.
There have been many reports in literature depicting that the
presence of heterocyclic moieties like thienyl, furyl, pyridyl
and pyrimidinyl at aforesaid position proves to be more
potent and efficacious than a simple aryl group (Rawal et al.,
2007; El-Gaby et al. 2009; Kaneria et al., 2003). These
observations coupled with the fact that pyrazole derivatives
(Kalluraya and Chimbalkar, 2001) possess wide spectrum of
biological activities; we directed our attention to synthesize
2,4-thiazolidinones having pyrazole moiety at their fifth
position.
Keywords Pyrazole ꢀ Thiazolidine-2,4-dione ꢀ
Antibacterial activity ꢀ Antifungal activity
O. Prakash (&) ꢀ D. K. Aneja ꢀ S. Arora
Department of Chemistry, Kurukshetra University,
Kurukshetra 136119, India
e-mail: dromprakash50@rediffmail.com
C. Sharma ꢀ K. R. Aneja
Department of Microbiology, Kurukshetra University,
Kurukshetra 136119, India
123

Med Chem Res (2012) 21:10–15
11
Chemistry
Table 1 Physical data of (Z)-5-((3-(aryl)-1-phenyl-1H-pyrazol-4-
yl)methylene)-3-phenylthiazolidine-2,4-diones (3a–i)
The starting material 3-phenylthiazolidine-2,4-dione (1)
was prepared according to literature procedure in two steps
starting from carbon disulphide and aniline (Furniss et al.,
1991; Brown, 1961; Momose et al., 1991). 4-Formylpy-
razoles (2) were prepared according to literature (Kira
et al., 1969) procedure involving Vilsmeier–Haack reac-
tion of various substituted acetophenone phenylhydrazones
using POCl3/DMF at 50–60°C for 4–5 h.
Compounds
Ar
MP (°C)
Yields %
3a
3b
3c
3d
3e
3f
C6H5
216–217
231–232
236–237
244–245
261–262
246–247
260–261
259–260
219–220
73
70
75
77
75
70
78
71
70
4-MeC6H4
4-OMeC6H4
4-ClC6H4
4-BrC6H4
4-FC6H4
3g
3h
3i
4-OHC6H4
4-NO2C6H4
2-Thienyl
5-((3-(Aryl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3-phe-
nylthiazolidine-2,4-diones (3a–i) were prepared according to
Scheme 1. Initially, Knoevenagel condensation was carried
out starting from 3-phenylthiazolidine-2,4-dione (1) and 1,3-
diphenyl-1H-pyrazole-4-carbaldehyde (2a) in ethanol in the
presence of catalytic amount of piperidine to give the desired
product (3a) as yellow solid in 73% yield (Scheme 1). We
studied the reaction of different 1-phenyl-3-aryl-1H-pyra-
zole-4-carbaldehydes (2b–i) with 3-phenylthiazolidine-2,4-
dione (1) under similar conditions, the reaction afforded
the desired products 3b–i in good yields. The geometry of
3a–i was assumed to be (Z)-isomer as observed in other
instances (Unangst et al., 1993). The physical data of these
synthesized products have been summarized in Table 1.
The structures of all the heterocyclic compounds 3
synthesized were confirmed by spectral (IR, NMR) and
elemental analyses. IR spectrum of product 3a displayed
disappearance of bands at 1674 cm-1 (due to C=O of
aldehyde) and appearance of 1744, 1697 (due to C=O of
154.92 (C3')
N
H
N
139.21 (C1'')
166.35 (C2)
H
O
S
O
N
165.19 (C4)
Fig. 1 Characteristic values of 13C spectrum of compound 3a
1
thiazolidinedione). The H NMR spectrum of 3a showed
singlets at d 8.047, 8.275 for the =CH proton and pyrazolyl
proton, respectively, apart from other aromatic signals. Its
13C spectrum showed signals at d 166.35, 165.19, 154.92
and 139.21 due to carbonyl groups C2 and C4 of thiazoli-
dine-2,4-dione, C3 of pyrazole and =CH carbon, respec-
tively, apart from other signals (Fig. 1).
both gram-positive (S. aureus and B. subtilis) bacteria. On
the basis of zone of inhibition produced against the test
bacterium, compound 3e (Ar = 4-BrC6H4) and 3i (Ar =
2-thienyl) were found to be most effective against S. aureus
showing the maximum zone of inhibition of 22 and 23 mm
and B. subtilis, producing 21 and 20 mm, respectively.
However, in case of gram-negative bacteria, none of the
compounds showed any activity as shown in Table 2. In
the whole series, the minimum inhibitory concentration
(MIC) of various tested chemical compounds ranged
between 32 and 128 lg/ml against gram-positive bacteria
(Fig. 2). The compounds 3e and 3i were found to be best,
showed the lowest MIC of 32 lg/ml against S. aureus and
compound nos. 3e, 3f and 3i showed the lowest MIC of
32 lg/ml against B. subtilis (Table 3). Of all the nine
compounds screened, compounds 3e and 3i were found to
be highly effective in inhibiting the growth of gram-posi-
tive bacteria.
Biological results and discussion
A total of nine compounds 3a–i were screened for their
antibacterial and antifungal activity. All the tested com-
pounds possessed variable antibacterial activity against
Ph
N
N
O
Ph
Ar
S
N
N
EtOH, Piperidine
reflux, 4-5 h
S
N
Ph
+
All the nine synthesized compounds tested for their
antifungal activity, five compounds, 3c–f and 3h showed
more than 50% inhibition against the A. flavus, whereas
three compounds 3a, 3d and 3f showed more than 50%
inhibition against A. niger. (Table 4).
H
Ar
O
N
Ph
CHO
O
O
1
3
2
Scheme 1
123

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Med Chem Res (2012) 21:10–15
Table 2 In vitro antibacterial activity of compounds (3a–i) through
agar well diffusion method
Table 4 In vitro antifungal activity of compounds (3a–i) through
poisoned food method
Compounds
Diameter of growth of inhibition zone (mm)a
Compounds
Mycelial growth inhibition (%)
S. aureus
B. subtilis
E. coli
P. aeruginosa
A. flavus
A. niger
3a
18.6
18.3
18.6
20.6
21.6
19.3
20.3
20.6
22.3
26.0
19.3
19.6
16.6
18.3
20.6
20.6
18.3
18.3
21.6
24.0
–
–
–
–
3a
50
55.5
44.4
50
3b
3b
50
3c
–
–
3c
66.6
61.1
55.5
55.5
44.4
61.1
33.3
77.7
3d
–
–
3d
55.5
38.8
55.5
50
3e
–
–
3e
3f
–
–
3f
3g
–
–
3g
3h
–
–
3h
50
3i
–
–
3i
50
Ciprofloxacin
25.0
22.0
Fluconazole
81.1
a
– No activity, values including diameter of the well (8 mm) are
means of three replicates
Experimental
Staphylococcus
aureus
Bacillus subtilis
All the reagents were purchased from commercial sources
and were used without further purification. Melting points
were taken on slides in an electrical apparatus Labindia
visual melting range apparatus and are uncorrected. 1H
NMR and 13C NMR spectra were recorded on a Brucker
300 MHz instrument using TMS as an internal standard. IR
spectra were recorded on a Perkin–Elmer 1800 FT-IR
spectrophotometer.
140
120
100
80
60
40
Preparation of (Z)-5-((3-(aryl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-phenylthiazolidine-2,4-diones (3)
20
0
General procedure
A mixture of 1,3-diphenyl-1H-pyrazol-4-carboxaldehyde
(2a, 1 g, 4 mmol) and 3-phenylthiazolidine-2,4-dione (1,
1.01 g, 5 mmol) in ethanol (20 ml) and 2–3 drops of piper-
idine, was refluxed 4–5 h. A solid was separated out of the
reaction mixture within 15–20 min and the refluxing was
continued for 4–5 h to complete the reaction. The reaction
mixture was cooled to room temperature, filtered and washed
with ethanol to give the pure product 3a (1.3 g, 76% yield).
The other derivatives 3b–i were synthesized by adopting
the similar procedure.
compounds/antibiotic
Fig. 2 Comparison of MIC of test compounds with antibiotic up to
MIC 128 (lg/ml)
Table 3 MIC (lg/ml) of compounds (3a–i) by using macro dilution
method
Compounds
S. aureus
B. subtilis
3a
128
128
128
64
64
64
3b
Characterization data of synthesized compounds (3a–i)
3c
128
128
32
3d
(Z)-3-Phenyl-5-((1,3-diphenyl-1H-pyrazol-4-yl)
methylene)thiazolidine-2,4-dione (3a)
3e
32
3f
128
64
32
3g
128
128
32
IR cm-1 (KBr): 1744, 1697, 1597, 1535, 1497, 1358, 1219,
1173, 1142 and 1065. 1H NMR d (300 MHz, CDCl3): 8.275
(s, 1H, Pyrazolyl-H), 8.047 (s, 1H CH=), 7.860–7.835 (m,
2H), 7.721–7.700 (m, 2H), 7.586–7.362 (m, 11H). 13C
3h
64
3i
32
Ciprofloxacin
5
5
123

Med Chem Res (2012) 21:10–15
13
NMR d (300 MHz, CDCl3): 166.35, 165.19, 154.92,
139.21, 132.81, 131.47, 129.71, 129.40, 129.24, 129.12,
128.97, 127.74, 127.38, 127.31, 125.55, 119.64, 119.42 and
116.24. Elemental analysis: calculated for C25H17N3O2S; C
70.90, H 4.05, N 9.92; Found C 70.75, H 3.98, N 9.99.
8.264 (s, 1H, Pyrazolyl-H), 7.973 (s, 1H CH=), 7.842–7.815
(m, 2H), 7.685–7.657 (m, 2H), 7.601–7.410 (m, 8H),
7.383–7.359 (m, 2H). 13C NMR d (300 MHz, CDCl3):
132.16, 130.39, 129.76, 129.41, 127.49, 127.26 and 119.69.
Elemental analysis: calculated for C25H16N3O2SF; C 59.88,
H 3.19, N 8.38; Found C 59.86, H 3.16, N 8.35.
(Z)-3-Phenyl-5-((1-phenyl-3-p-tolyl-1H-pyrazol-4-yl)
methylene)thiazolidine-2,4-dione (3b)
(Z)-5-((3-(4-Fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-phenylthiazolidine-2,4-dione (3f)
IR cm-1 (KBr): 1744, 1690, 1605, 1497, 1450, 1358, 1227,
1
1149 and 1072. H NMR d (300 MHz, CDCl3): 8.260 (s,
IR cm-1 (KBr): 1744, 1690, 1597, 1497, 1450, 1358, 1227,
1
1H, Pyrazolyl-H), 8.041 (s, 1H CH=), 7.855–7.827 (m,
2H), 7.611–7.326 (m, 12H), 2.452 (s, 1H, CH3). 13C NMR
d (300 MHz, CDCl3): 166.39, 165.19, 155.00, 139.25,
139.11, 132.84, 129.67, 129.38, 129.21, 128.83, 128.58,
127.65, 127.32, 125.73, 119.61, 119.19, 116.19 and 21.39.
Elemental analysis: calculated for C26H19N3O2S; C 68.64,
H 4.34, N 9.61; Found C 68.58, H 4.27, N 9.71.
1142 and 1065. H NMR d (300 MHz, CDCl3): 8.264 (s,
1H, Pyrazolyl-H), 7.980 (s, 1H CH=), 7.845–7.819 (m,
2H), 7.712–7.666 (m, 2H), 7.627–7.357 (m, 8H),
7.282–7.201 (m, 2H). 13C NMR d (300 MHz, CDCl3):
166.21, 165.16, 153.95, 139.16, 132.73, 130.80, 130.69,
129.75, 129.41, 129.28, 127.86, 127.62, 127.41, 127.27,
125.09, 119.67, 116.20, 116.15 and 115.91. Elemental
analysis: calculated for C25H16N3O2SF; C 68.02, H 3.63, N
9.52; Found C 68.00, H 3.64, N 9.53.
(Z)-5-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-phenylthiazolidine-2,4-dione (3c)
(Z)-5-((3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-phenylthiazolidine-2,4-dione (3g)
IR cm-1 (KBr): 1744, 1690, 1605, 1520, 1450, 1350, 1296,
1
1250 and 1165. H NMR d (300 MHz, CDCl3): 8.248 (s,
1H, Pyrazolyl-H), 8.030 (s, 1H CH=), 7.847–7.821 (m,
2H), 7.657–7.628 (d, 2H, J = 8.7 Hz), 7.576–7.478 (m,
5H), 7.453–7.361 (m, 3H), 7.073–7.044 (d, 2H,
J = 8.7 Hz), 3.893 (s, 3H, OCH3). 13C NMR d (300 MHz,
CDCl3): 166.40, 165.22, 160.40, 154.80, 139.25, 132.79,
130.22, 129.70, 129.39, 129.23, 127.67, 127.30, 125.78,
123.90, 119.62, 119.09, 116.08, 114.45 and 55.41. Ele-
mental analysis: calculated for C26H19N3O3S; C 66.25, H
4.05, N 8.95; Found C 66.30, H 4.09, N 8.94.
IR cm-1 (KBr): 3279, 1728, 1666, 1605, 1528, 1497, 1435,
1358, 1273, 1196, 1173, 1142 and 1072. 1H NMR d
(300 MHz, DMSO-d6): 9.253 (bs, 1H, OH), 8.205 (s, 1H,
Pyrazolyl-H), 7.891 (s, 1H CH=), 7.749–7.746 (m, 2H),
7.433–7.284 (m, 10H), 6.911–6.895 (m, 2H). 13C NMR d
(300 MHz, DMSO-d6): 167.12, 165.41, 158.81, 154.47,
139.26, 133.58, 130.55, 130.07, 129.60, 128.46, 127.85,
124.29, 122.38, 120.30, 119.78, 116.24 and 115.65. Ele-
mental analysis: calculated for C25H17N3O3S; C 68.33, H
3.87, N 9.56; Found C 68.35, H 3.84, N 9.52.
(Z)-5-((3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-phenylthiazolidine-2,4-dione (3d)
(Z)-5-((3-(4-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-phenylthiazolidine-2,4-dione (3h)
IR cm-1 (KBr): 1744, 1690, 1628, 1597, 1535, 1498, 1450,
1358, 1219, 1173, 1142, 1095 and 1065. 1H NMR d
(300 MHz, CDCl3): 8.260 (s, 1H, Pyrazolyl-H), 7.974 (s,
1H CH=), 7.838–7.813 (m, 2H), 7.666–7.638 (m, 2H),
7.584–7.429 (m, 8H), 7.404–7.358 (m, 2H). 13C NMR d
(300 MHz, CDCl3): 166.18, 165.11, 153.67, 139.14,
135.31, 132.72, 130.14, 129.97, 129.76, 129.42, 129.29,
129.21, 127.91, 127.48, 127.26, 124.90, 119.92, 119.69 and
116.20. Elemental analysis: calculated for C25H16N3O2SCl;
C 65.57, H 3.49, N 9.18; Found C 65.54, H 3.46, N 9.15.
IR cm-1 (KBr): 1744, 1697, 1597, 1528, 1504, 1358, 1227,
1149, 1111 and 1080. 1H NMR d (300 MHz, CDCl3):
8.415–8.384 (d, 2H, J = 8.7 Hz), 8.307 (s, 1H, Pyrazolyl-H),
7.980 (s, 1H CH=), 7.936–7.907 (d, 2H, J = 8.7),
7.861–7.830 (m, 2H), 7.617–7.443 (m, 6H), 7.390–7.361 (m,
2H). 13C NMR d (300 MHz, CDCl3): 137.93, 129.86, 129.56,
129.46, 128.27, 127.81, 127.22, 124.19, 123.90, 119.78 and
116.58. Elemental analysis: calculated for C25H17N4O4S; C
63.96, H 3.62, N 11.94; Found C 63.92, H 3.61, N 11.92.
(Z)-5-((3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-4-yl)
methylene)-3-phenylthiazolidine-2,4-dione (3e)
(Z)-3-Phenyl-5-((1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-
yl)methylene)thiazolidine-2,4-dione (3i)
IR cm-1 (KBr): 1744, 1690, 1605, 1528, 1497, 1443, 1366,
1219, 1165, 1072 and 1011. 1H NMR d (300 MHz, CDCl3):
IR cm-1 (KBr): 1744, 1690, 1597, 1528, 1497, 1458, 1404,
1
1358, 1296, 1234, 1196, 1149, 1072 and 1049. H NMR d
123

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Med Chem Res (2012) 21:10–15
(300 MHz, CDCl3): 8.232 (s, 1H, Pyrazolyl-H), 8.194 (s,
1H CH=), 7.836–7.809 (m, 2H), 7.579–7.371 (m, 10H),
7.213–7.184 (m, 2H). 13C NMR d (300 MHz, CDCl3):
166.21, 165.13, 148.85, 139.02, 133.09, 132.77, 129.71,
129.39, 129.25, 128.85, 128.63, 127.98, 127.86, 127.53,
127.43, 127.28, 127.17, 124.80, 119.97, 119.65 and 116.04.
Elemental analysis: calculated for C23H15N3O2S2; C 64.33,
H 3.49, N 9.79; Found C 64.31, H 3.47, N 9.77.
synthesized compounds were made from 128 to 0.25 lg/ml
in sterile tubes no. 1–10. 100 ll sterile Mueller–Hinton
Broth (MHB) was poured in each sterile tube followed by
the addition of 200 ll test compound in tube 1. Twofold
serial dilutions were carried out from the tube no. 1 to the
tube no. 10 and excess broth (100 ll) was discarded from
the last tube no. 10. To each tube, 100 ll of standard
inoculums (1.5 9 108 CFU/ml) was added. Ciprofloxacin
was used as control. Turbidity was observed after incu-
bating the inoculated tubes at 37°C for 24 h.
Biological assay
In vitro antifungal activity
Test microorganisms
The antifungal activity of the synthesized compounds was
evaluated by poisoned food technique. The moulds were
grown on Sabouraud dextrose agar (SDA) at 25°C for 7 days
and used as inocula. 15 ml of molten SDA (45°C) was
poisoned by the addition of 100 ll volume of each com-
pound having concentration of 4.0 mg/ml, reconstituted in
the DMSO, poured into a sterile petri plate and allowed it to
solidify at room temperature. The solidified poisoned agar
plates were inoculated at the centre with fungal plugs (8 mm
diameter), obtained from the actively growing colony and
incubated at 25°C for 7 days. DMSO was used as the neg-
ative control whereas fluconazole was used as the positive
control. The experiments were performed in triplicates.
Diameter of the fungal colonies was measured and expres-
sed as percent mycelial inhibition determined by applying
the formula (Al-Burtamani et al., 2005).
Four bacteria, S. aureus (MTCC 96), B. subtilis (MTCC
121) (gram-positive), E. coli (MTCC 1652) and P. aeru-
ginosa (MTCC 741) (gram-negative) procured from
MTCC, Chandigarh and two fungi, A. niger and A. flavus,
the ear pathogens isolated from the Kurukshetra patients,
were used in this study.
In vitro antibacterial activity
The antibacterial activity of synthesized compounds was
evaluated by the agar well diffusion method. All the cul-
tures were adjusted to 0.5 McFarland standard, which is
visually comparable to a microbial suspension of approx-
imately 1.5 9 108 CFU/ml. 20 ml of Mueller–Hinton agar
medium was poured into each petri plate and the agar
plates were swabbed with 100 ll inocula of each test
bacterium and kept for 15 min for adsorption. Using sterile
cork borer of 8 mm diameter, wells were bored into the
seeded agar plates and these were loaded with a 100 ll
volume with concentration of 4.0 mg/ml of each compound
reconstituted in the dimethylsulphoxide (DMSO). All the
plates were incubated at 37°C for 24 h. Antibacterial
activity of each synthetic compound was evaluated by
measuring the zone of growth inhibition against the test
organisms with zone reader (Hi Antibiotic zone scale).
DMSO was used as a negative control whereas ciproflox-
acin was used as a positive control. This procedure was
performed in three replicate plates for each organism
(Ahmad and Beg, 2001; Andrews, 2001).
Inhibition of mycelial growth% ¼ ðdc ꢁ dtÞ=dc ꢂ 100
where, dc = average diameter of fungal colony in negative
control plates, dt = average diameter of fungal colony in
experimental plates.
Acknowledgments We are thankful to Council of Scientific and
Industrial Research (CSIR 01(2186)/07/EMR-II), New Delhi for
providing financial assistance to carry out this work.
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