One-pot multicomponent synthesis of indole incorporated thiazolylcoumarins and their antibacterial, anticancer and DNA cleavage studies

Article abstract of DOI:10.1016/j.bmcl.2014.10.100

A series of indole incorporated thiazolylcoumarins (7a-q) have been synthesized and evaluated for their antibacterial, anticancer and DNA cleavage studies. Analysis of antibacterial studies indicated that all the synthesized compounds possess promising activity towards the screened bacterial strains. In vitro anticancerous action was studied for compound 7a (NSC: 768621/1) against the full panel of 60 human tumor cell lines. The five dose level activity results revealed that, the compound 7a was active against all the cell lines among them it has shown potent activity against Leukemia: CCRF-CEM (GI₅₀: 0.33 μM), Non-Small Cell Lung Cancer: NCI-H522 (GI₅₀: 1.03 μM), Colon Cancer: HCT-116 (GI₅₀: 1.60 μM), CNS Cancer: SF-539 (GI₅₀: 1.58 μM), Melanoma MALME-3M (GI₅₀: 1.59 μM), Ovarian Cancer: OVCAR-3 (GI₅₀: 1.16 μM), Renal Cancer: UO-31 (GI₅₀: 0.76 μM), Prostate Cancer: PC-3 (GI₅₀: 0.82 μM) and Breast Cancer: BT-549 (GI₅₀: 1.13 μM). DNA cleavage studies revealed that even at 50 μg/mL concentration complete DNA digestion was observed for all the compounds, except for compound (7o) where partial DNA digestion was observed even at 100 μg/mL.

Full text of DOI:10.1016/j.bmcl.2014.10.100

Accepted Manuscript
One-pot multicomponent synthesis of indole incorporated thiazolylcoumarins
and their antibacterial, anticancer and DNA cleavage studies
Rajitha Gali, Janardhan Banothu, Ramesh Gondru, Rajitha Bavantula,
Yashodhara Velivela, Peter. A. Crooks
PII:
S0960-894X(14)01171-8
DOI:
http://dx.doi.org/10.1016/j.bmcl.2014.10.100
BMCL 22155
Reference:
Bioorganic & Medicinal Chemistry Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 June 2014
27 October 2014
31 October 2014
Please cite this article as: Gali, R., Banothu, J., Gondru, R., Bavantula, R., Velivela, Y., Crooks, r.A., One-pot
multicomponent synthesis of indole incorporated thiazolylcoumarins and their antibacterial, anticancer and DNA
cleavage studies, Bioorganic & Medicinal Chemistry Letters (2014), doi: http://dx.doi.org/10.1016/j.bmcl.
2014.10.100
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One-pot multicomponent synthesis of indole
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incorporated thiazolylcoumarins and their
antibacterial, anticancer and DNA cleavage studies
Rajitha Gali,a Janardhan Banothu,a Ramesh Gondru,a Rajitha Bavantula,a* Yashodhara Velivela,b Peter. A.
Crooksc
1
*Corresponding author: Tel: 0091-0870-2459445; Fax: 0091-0870-2459547
E-mail: rajitabhargavi@yahoo.com

Bioorganic & Medicinal Chemistry Letters
journal homepage: www.els evier.com
One-pot multicomponent synthesis of indole incorporated thiazolylcoumarins
and their antibacterial, anticancer and DNA cleavage studies
Rajitha Gali,a Janardhan Banothu,a Ramesh Gondru,a Rajitha Bavantula,a* Yashodhara Velivela,b Peter. A. Crooksc
aDepartment of Chemistry, National Institute of Technology, Warangal-506004, Telangana, India.
bDepartment of Bio-Technology, Kakatiya University, Warangal-506009, Telangana, India
cDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
ARTICLE INFO
ABSTRACT
A series of indole incorporated thiazolylcoumarins (7a-q) have been synthesized and evaluated for
their antibacterial, anticancer and DNA cleavage studies. Analysis of antibacterial studies indicated
that all the synthesized compounds possess promising activity towards the screened bacterial strains.
In vitro anticancerous action was studied for compound 7a (NSC: 768621/1) against the full panel of
60 human tumor cell lines. The five dose level activity results revealed that, the compound 7a was
active against all the cell lines among them it has shown potent activity against Leukemia: CCRF-
CEM (GI50: 0.33 µM), Non-small cell lung cancer: NCI-H522 (GI50: 1.03 µM), Colon Cancer: HCT-
116 (GI50: 1.60 µM), CNS Cancer: SF-539 (GI50: 1.58 µM), Melanoma MALME-3M (GI50: 1.59µM),
Ovarian Cancer: OVCAR-3 (GI50: 1.16 µM), Renal Cancer: UO-31 (GI50: 0.76 µM), Prostate Cancer:
PC-3 (GI50: 0.82 µM) and Breast Cancer: BT-549 (GI50: 1.13µM). DNA cleavage studies revealed that
even at 50 µg/mL concentration complete DNA digestion was observed for all the compounds, except
for compound (7o) where partial DNA digestion was observed even at 100µg/mL.
Article history:
Received
Revised
Accepted
Available online
Keywords:
Antibacterial activity
Anticancer activity
DNA cleavage studies
Indoles
Thiazolyl coumarins
2009 Elsevier Ltd. All rights reserved
Cancer is a potential life-threatening disease characterized by
the uncontrolled growth of abnormal cells. About 12.7 million
cancer cases and 7.6 million cancer deaths (13%) are estimated to
have occurred in 2008 world-wide.1 DNA is the primary target
molecule for most of the anticancer and antiviral therapies; DNA
damage, mutation and altered gene expression are key players in
the process of carcinogenesis. Many natural and synthetic
anticancer agents having ability to interact with DNA have been
discovered.2 Indole, thiazole and coumarin moieties are endowed
with anticancer, anticonvulsant, antitubercular, antimicrobial,
antioxidant and anti-inflammatory activities.3 Some of the widely
used anticancer drugs such as Cediranib, Tiazofurin, and
Geiparvarin as well as most active thiazolylcoumarin derivatives4
are shown in (Fig 1).
N
O
N
O
CH3
NH2
N
N
O
H3CO
O
H3C
H3C
O
O
O
HO
O
F
S
HO
O
OH
HN
H3C
(iii)
Geiparvarin
(ii)
Tiazof urin
(i) Cediranib
R1
H
N
Br
S
N
N
O
R2
S
NH
N
NH
N
O
OH
S
Ar
N
NH
N
X
N
O
O
O
O
CH3
O
O
(vii) Ar = 2,4-Dichlorophenyl, X = H
(viii) Ar = 2,4-Dichlorophenyl, X = Br
(vi)
(iv) R1 = H, R2 = Br
(v) R1 = OH, R2 = H
(ix)
(x)
Ar = 2,5-Dichlorothiophene, X = H
Ar = 2,5-Dichlorothiophene, X = Br
Fig. 1. Some of the widely used anticancer drugs (i, ii & iii) and potent
antimicrobial thiazolylcoumarin derivatives (iv to x).
Multi-component reactions (MCRs) have emerged as an
efficient and powerful tool in modern synthetic organic chemistry
in which three or more different starting materials react to give a
final product in a one-pot procedure.5 Several methods have been
reported for the synthesis of thiazolylhydrazones4,6 in multistep
process, for longer reaction times. In the present study and in
continuation of our research towards the synthesis of biologically
potent heterocyclic compounds,7 we opted to design a moiety that
embodied indole, thiazole and coumarin in a single frame via
multicomponent approach and their antibacterial, anticancer and
DNA cleavage activities were evaluated.
A series of indole incorporated thiazolylcoumarins (7a-q)
were synthesized via multicomponent condensation of 3-(2-
bromoacetyl)-2H-chromen-2-ones (4a-d)/2-(2-bromoacetyl)-3H-
benzo[f]chromen-3-one (4e), indole-3-carbaldehyde (5a-e) and
thiosemicarbazide (6) in absolute ethanol with catalytic amount
of acetic acid under reflux conditions with 84-97% yield.8 The
synthetic pathway was outlined in Scheme 1. Indole-3-
carbaldehydes (5a-e) and 3-(bromoacetyl)-2H-chromen-2-ones
(4a-d)/2-(2-bromoacetyl)-3H-benzo[f]chromen-3-one (4e) were
synthesized according to the literature methods.9
2

All the newly synthesized compounds were characterized by
IR, NMR and mass spectral studies as well as elemental analyses.
In the IR spectrum of compound (7a), the appearance of a broad
band in the range of 3150-3300 cm-1, sharp bands at 1720, 1623
cm-1, and a medium band at 1105 cm-1 corresponds to N-H, C=O,
the singlets at 11.55 and 11.89 ppm confirm the hydrazinyl and
indole NH protons respectively. 13C NMR, spectroscopic
analyses also confirmed the structural identity, with resonances
observed at 168.55, 159.21, 154.87, 144.29 ppm corresponding
to thiazolyl carbon, δ-lactone carbonyl carbon, coumarin 4th
carbon, and imine carbons respectively. Molecular ion peak from
the mass spectrum as well as elemental analyses further
confirmed the product formation.
1
C=N and C-S stretching frequencies respectively. In case of H
NMR spectrum, the singlets at 8.32 and 8.57 ppm confirm the
presence of imine and coumarin 4th protons respectively, whereas
Scheme 1. Synthesis of indole incorporated thiazolylcoumarins.
All the synthesized compounds (7a-q) were screened for their in
vitro antibacterial activity against Bacillus subtilis (Gram
positive) and Escherichia coli (Gram negative) bacterial strains
with respect to standard antibiotic drug Streptomycin using cup-
plate agar diffusion method.10 The activity was performed at 50
µg/mL for 7a-q and 30 µg/mL for Streptomycin, and the
resulting zone of inhibition (ZOI) were given in Table 1. The
activity results (Table 1) revealed that, the compound without
having any substitutions (7a) on coumarin, thiazole and indole
moieties has shown maximum ZOI against Escherichia coli (ZOI
= 18 mm) and good ZOI against Bacillus subtilis (ZOI = 15 mm).
Except compound derived from 6,8-dibromo-3-(2-bromoacetyl)-
2H-chromen-2-one and 1H-indole-3-carbaldehyde i.e. 7f and 3-
(2-bromoacetyl)-6-chloro-2H-chromen-2-one and 2-methyl-1H-
indole-3-carbaldehyde i.e. 7q against Escherichia coli, remaining
all the compounds have also shown good ZOI ranging from 10-
15 mm against both the tested bacterial strains.
(less than 0) can be detected. The results were analyzed by
COMPARE program.12 The percentage growth inhibition (GI%)
of the treated cells 10-5 M concentration with the compound 7a is
given in Table 2.
Table 1. Zone of inhibition values for analogs (7a-q) at 50
µg/mL and positive control drug Streptomycin at 30 µg/mL.
Entry
Product
Zone of inhibition in mm
Bacillus subtilis Escherichia coli
18 15
1
2
7a
7b
13
13
15
15
10
10
10
10
10
15
13
15
15
15
15
10
30
10
10
14
13
7
3
7c
4
7d
5
7e
6
7f
7
7g
10
10
12
10
15
15
12
12
12
10
6
8
7h
9
7i
10
11
12
13
14
15
16
17
18
7j
7k
In vitro anticancer activity was carried out at National
Cancer Institute, Bethesda, USA.11 Among all the compounds 7a
was selected by NCI and initially screened at a single high dose
of 10-5 M concentration on all the 60 human cancer cell lines was
organized into nine sub-panels derived from nine different human
cancer types: Leukemia, Lung, Colon, CNS, Melanoma, Ovarian,
Renal, Prostate and Breast cancer cell lines. Output from the
single dose screen is reported as a graph of mean growth percent
of the treated cells (supporting file). From the graph both growth
inhibition values (between 0 and 100) and cytotoxicity values
7l
7m
7n
7o
7p
7q
Streptomycin
30
Bacillus subtilis:- Resistant: 7a, 7d, 7e, 7k, 7m, 7n, 7o, 7p; Intermediate: 7b,
7c, 7f, 7g, 7h, 7i, 7j, 7l, 7q.
Escherichia coli:- Resistant: 7a, 7d, 7k, 7l; Intermediate: 7b, 7c, 7e, 7g, 7h,
7i, 7j, 7m, 7n, 7o, 7p; Susceptible: 7f, 7q.
3
*Corresponding author: Tel: 0091-0870-2459445; Fax: 0091-0870-2459547
E-mail: rajitabhargavi@yahoo.com

Table 2. Growth percent and growth inhibition (GI%) in
single dose assay (10-5 M) for compound 7a (NSC:
768621/1).
Table 3. GI50, TGI and LC50 values of compound 7a against
60 human cancer cell lines.
Panel/ Cell line
GI50 (µM)
MGMID (µM)
TGI (µM)
LC50 (µM)
Leukemia
CCRF-CEM
HL-60(TB)
K-562
MOLT-4
RPMI-8226
SR
Non-Small Cell
Lung Cancer
A549/ATCC
HOP-62
Panel/ Cell line
Growth percent
Growth inhibition (GI%)
0.33
0.45
3.18
0.40
0.90
1.83
1.78
7.64
10.4
3.27
4.79
4.92
> 100
> 100
> 100
> 100
> 100
> 100
Leukemia
CCRF-CEM
HL-60(TB)
K-562 0.99
MOLT-4
-26.91
-28.24
0.99
-32.32
-33.83
-0.54
cytotoxic
cytotoxic
99.01
cytotoxic
cytotoxic
cytotoxic
1.18
RPMI-8226
SR
Non-Small Cell Lung
Cancer
1.54
3.73
2.38
2.44
3.16
2.84
1.03
5.30
20.0
7.70
5.82
32.2
9.69
2.26
> 100
> 100
> 100
> 100
> 100
> 100
4.96
A549/ATCC
HOP-62
HOP-92
-30.98
11.30
-14.45
42.82
25.93
15.29
5.79
cytotoxic
88.7
cytotoxic
57.18
74.07
84.71
94.21
cytotoxic
NCI-H226
NCI-H23
NCI-H322M
NCI-H460
NCI-H522
Colon Cancer
COLO 205
HCC-2998
HCT-116
HCT-15
2.44
NCI-H226
NCI-H23
NCI-H322M
NCI-H460
NCI-H522
Colon Cancer
COLO 205
HCC-2998
HCT-116
HCT-15
1.92
2.82
1.60
1.61
2.01
1.86
2.19
3.55
6.80
3.22
3.47
5.55
4.14
5.24
6.55
> 100
6.49
-77.80
28.15
8.49
7.48
71.85
91.51
92.52
2.00
7.46
HT29
KM12
SW-620
> 100
9.22
70.9
12.32
32.14
-47.67
17.50
87.68
67.86
HT29
KM12
SW-620
CNS Cancer
SF-268
SF-295
cytotoxic
82.50
1.93
2.23
1.58
3.39
2.00
1.75
8.77
6.76
3.38
62.1
8.92
5.60
> 100
> 100
7.25
CNS Cancer
SF-268
SF-295
SF-539
SNB-19
2.14
14.73
-25.04
0.41
85.27
cytotoxic
99.59
> 100
> 100
77.7
SNB-75
U251
SF-539
SNB-19
39.43
15.44
-6.38
60.57
84.56
cytotoxic
Melanoma
LOX IMVI
MALME-3M
M14
SNB-75
U251
1.93
1.59
1.95
2.10
1.61
3.96
2.09
2.15
1.60
3.60
4.17
4.22
5.47
3.62
96.9
4.97
5.63
3.38
6.71
> 100
9.13
Melanoma
LOX IMVI
MALME-3M
M14
-52.19
-10.02
34.19
22.44
-9.49
54.83
69.78
8.34
cytotoxic
cytotoxic
65.81
MDA-MB-435
SK-MEL-2
SK-MEL-28
SK-MEL-5
UACC-257
UACC-62
Ovarian Cancer
IGROV1
25.2
8.17
> 100
15.2
2.10
MDA-MB-435
SK-MEL-2
SK-MEL-28
SK-MEL-5
UACC-257
UACC-62
Ovarian Cancer
IGROV1
OVCAR-3
OVCAR-4
OVCAR-5
OVCAR-8
NCI/ADR-RES
SK-OV-3
Renal Cancer
786-0
77.56
cytotoxic
45.17
30.22
> 100
7.11
91.66
57.04
1.54
1.16
1.37
2.34
1.90
2.82
3.95
4.70
2.91
5.87
7.80
4.56
9.23
> 100
> 100
7.31
42.96
OVCAR-3
OVCAR-4
OVCAR-5
OVCAR-8
NCI/ADR-RES
SK-OV-3
Renal Cancer
786-0
> 100
> 100
> 100
> 100
> 100
0.26
-80.31
-4.09
55.24
2.99
99.74
cytotoxic
cytotoxic
44.76
2.15
97.01
75.10
37.76
24.90
62.24
1.35
2.21
1.31
1.61
1.97
1.08
0.76
4.09
8.20
4.36
4.65
4.77
3.96
2.23
> 100
> 100
70.8
A498
ACHN
CAKI-1
-53.65
6.72
cytotoxic
93.28
89.93
1.47
1.31
> 100
33.9
A498
ACHN
CAKI-1
RXF 393
SN12C
UO-31
10.07
-41.32
25.19
0.22
> 100
5.47
cytotoxic
74.81
99.78
RXF 393
SN12C
UO-31
Prostate Cancer
PC-3
DU-145
0.828
1.80
2.66
4.27
7.63
> 100
-90.51
cytotoxic
Prostate Cancer
PC-3
DU-145
Breast Cancer
MCF7
Breast Cancer
MCF7
-37.33
-36.09
cytotoxic
cytotoxic
2.40
1.39
15.5
3.33
> 100
7.94
MDA-MB-
231/ATCC
HS 578T
8.91
-37.04
91.09
cytotoxic
3.20
1.13
1.98
1.52
1.93
58.9
2.43
5.90
3.92
> 100
5.22
MDA-MB-
231/ATCC
BT-549
BT-549
T-47D
MDA-MB-468
> 100
> 100
-12.14
4.07
2.39
cytotoxic
95.93
97.61
T-47D
MDA-MB-468
4
*Corresponding author: Tel: 0091-0870-2459445; Fax: 0091-0870-2459547
E-mail: rajitabhargavi@yahoo.com

The compound 7a has shown significant growth inhibition at
a single dose of 10-5 M concentration and it has been further
evaluated for five dose screening at five different minimal
concentrations against full 60 cell lines. Dose-response curves of
compound 7a were created by plotting cytotoxic effect against
the log10 of the drug concentration for each cell line (Fig. 2).
Cytotoxic effects of each compound were determined as GI50,
TGI and LC50 values. The compound 7a has exhibited broad
spectrum of growth inhibition activity against nine tumor cell
lines with average GI50 values (MGMID) 1.18-2.44 µM as shown
in (Table 3).
compound 7o and 7h remaining all the compounds have shown
complete DNA cleavage even at 50 µg/mL concentration.
Compound 7o has partially cleaved the DNA at both the
concentrations, and compound 7h has partially cleaved the DNA
at 50 µg/mL and completely cleaved at 100 µg/mL. From this, it
can be concluded that almost all the compounds (except 7o and
7h) inhibit the growth of the pathogenic organism by cleaving the
genome.
Fig. 3. Agarose gel DNA cleavage analysis of compound 7(a-q) using pUC18
plasmid; Where, M-standard DNA molecular weight marker; P-pUC18
plasmid DNA; FeSO4-pUC18 plasmid with 5 mM FeSO4; Remaining all
lanes: pUC18 plasmid with compound (7a-q) at 50 and 100 µg/mL
concentrations.
In conclusion,
a
series of indole incorporated
synthesized via one-pot
thiazolylcoumarins
were
multicomponent approach with good yields. All the synthesized
compounds were screened for their in vitro antibacterial and
DNA cleavage activities, and anticancer activity of compound 7a
was also evaluated. Antibacterial results revealed that, the
compounds 7a, 7d, 7e, 7k, 7l, 7m, 7n and 7o exhibited broad
spectrum antibiotic activity at 50 µg/mL. DNA cleavage studies
have shown that all the compounds exhibit promising DNA
cleavage activity at 50 and 100 µg/mL concentration except
compound 7o and 7h. The primary anticancer screening of
compound 7a was carried at 10-5 M concentration and the results
have shown 50-99% growth inhibition against all the 60 human
tumor cell lines, thus it was further selected for fifth dose level
and screened against all the cell lines. Even at fifth dose level, it
has exhibited marked anticancer activity in µM concentration
Fig. 2. Dose response curve of nine sub-panel cell lines for compound 7a.
The DNA cleavage activity on pUC18 was carried out at 50
and 100 µg/mL concentrations using agarose gel electrophoresis
method.13 The pictures of the gels are presented in (Fig. 3).
Results have been compared with the standard DNA cleavage
agent FeSO4. From these results we noticed that, except
5
*Corresponding author: Tel: 0091-0870-2459445; Fax: 0091-0870-2459547
E-mail: rajitabhargavi@yahoo.com

3-(2-(2-((1H-Indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)2H-chromen-
against all the cell lines. Therefore these studies provide a new
lead compound for further development of more potent
antibacterial and anticancer agents.
2-one (7a): Yellow solid; Yield: 97%; mp: 248-250 oC; IR (KBr, υmax cm
1): 3229, 3158 (N-H), 1720 (C=O), 1623 (C=N), 1576 (C=C), 1105 (C-
S); 1H NMR (400 MHz, DMSO-d6): δ 7.19-7.24 (m, 2H), 7.38-7.47 (m,
3H), 7.64 (t, J = 7.6 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.0
Hz, 1H), 8.23 (d, J = 7.2 Hz, 1H), 8.32 (s, 1H), 8.57 (s, 1H), 11.55 (s,
1H), 11.89 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 168.55, 159.21,
154.87, 152.72, 144.29, 140.32, 138.49, 132.33, 132.04, 130.41, 130.28,
129.27, 125.15, 124.96, 121.06, 119.67, 116.29, 112.88, 111.72, 110.33,
103.81; MS (ESI) m/z: 387 [M + H]+; HRMS for C21H14N4O2S: Calcd.
386.0837; Found 386.0835; Anal. calcd. for: C, 65.27; H, 3.65; N, 14.50;
Found: C, 65.35; H, 3.62; N, 14.33.
-
Acknowledgements
The authors wish to thank the Director, National Institute of
Technology, Warangal for providing infrastructure and professor
F. A. Khan, IIT Hyderabad for his helping hand in providing
HRMS. One of the authors RG thanks to UGC providing
research fellowships. We are grateful to NCI/NIH, Bethesda,
USA for performing the antitumor testing of the synthesized
compounds.
3-(2-(2-((2-Methyl-1H-indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)2H-
chromen-2-one (7b): Yellow solid; Yield: 95%; mp: 264-266 oC; IR
(KBr, υmax cm-1): 3416, 3187 (N-H), 1702 (C=O), 1618, 1604 (C=N),
1576 (C=C), 1103 (C-S); 1H NMR (400 MHz, DMSO-d6): δ 2.50 (s, 3H),
7.11-7.14 (m, 2H), 7.32-7.46 (m, 3H), 7.61 (d, J = 7.6 Hz, 1H), 7.74 (s,
1H), 7.86 (d, J = 7.6 Hz, 1H), 8.11 (t, J = 7.2 Hz, 1H), 8.35 (s, 1H), 8.56
(s, 1H), 11.44 (s, 1H), 11.72 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ
167.88, 158.69, 152.28, 142.80, 140.03, 139.35, 138.27, 135.70, 131.70,
128.79, 125.11, 124.72, 121.75, 120.55, 120.35, 120.08, 119.11, 115.86,
110.93, 109.71, 107.18, 11.50; MS (ESI) m/z: 401 [M + H]+; Anal. calcd.
for C22H16N4O2S: C, 65.98; H, 4.03; N,13.99; Found: C, 65.87; H, 4.18;
N, 14.09.
Supplementary data
Supplementary data (NCI anticancer activity data and
characterization data of all compounds) associated with this
article can be found, in the online version, at.....
References and notes
1. (a) Bagi, C. M. J. Musculoskel. Neuron Interact. 2002, 2, 579; (b)
Mehlen, P.; Puisieux, A. Nat. Rev. Cancer 2006, 6, 449; (c) Simpson, C.
D.; Anyiwe, K.; Schimmer, A. D. Cancer Lett. 2008, 272, 177.
2. Riou, J. F.; Fosse, P.; Nguyen, C. H.; Larsen, A. K.; Bissery, M. C.;
Grondard, L.; Saucier, J. M.; Bisagni, E.; Lavelle, F. Cancer Res. 1993,
53, 5987.
3-(2-(2-((5-Methoxy-1H-indol-3-yl)methylene)hydrazinyl)thiazol-4-
yl)2H-chromen-2-one (7c): Green solid; Yield: 97%; mp: 262-264 oC; IR
(KBr, υmax cm-1): 3411, 3273 (N-H), 1698 (C=O), 1619 (C=N), 1577
(C=C), 1098 (C-S); 1H NMR (400 MHz, DMSO-d6): δ 3.87 (s, 3H), 6.84-
6.87 (m, 1H), 7.34 (d, J = 8.8 Hz ,2H), 7.41 (d, J = 7.2 Hz, 1H), 7.46 (d,
J = 8.4 Hz, 1H), 7.62 (d, J = 7.2 Hz, 3H), 7.72-7.87 (m, 1H), 8.27 (s,
1H), 8.56 (s, 1H), 11.38 (s, 1H), 11.83 (s, 1H); MS (ESI) m/z: 417 [M +
H]+; Anal. calcd. for C22H16N4O3S: C, 63.45, H, 3.87; N,13.45; Found: C,
63.55, H, 3.72; N,13.31.
3. (a) Weng, J. R.; Tsai, C. H.; Kulp, S. K.; Chen, C. S. Cancer Lett. 2008,
262, 153; (b) Bialonska, D.; Zjawiony, J. K. Mar. Drugs 2009, 7, 166; (c)
Rosenbaum, C.; Rohrs, S.; Muller, O.; Waldmann, H. J. Med. Chem.
2005, 48, 1179; (d) Kumar, D.; Sundaree, S.; Johnson, E. O.; Shah, K.
Bioorg. Med. Chem. Lett. 2009, 19, 4492; (e) Kashyap, M.; Kandekar, S.;
Baviskar, A. T.; Das, D.; Preet, R.; Mohapatra, P.; Satapathy, S. R.;
Siddharth, S.; Guchhait, S. K.; Kundu, C. N.; Banerje, U. C. Bioorg.
Med. Chem. Lett. 2013, 23, 934; (f) Reddy, Y. T.; Sekhar, K. R.; Sasi,
N.; Reddy, P. N.; Freeman, M. L.; Crooks, P. A. Bioorg. Med. Chem.
Lett. 2010, 20, 600; (g) Sonar, V. N.; Thirupathi reddy, Y.; Sekhar, K. R.;
Sasi, S.; Freeman, M. L.; Crooks, P. A. Bioorg. Med. Chem. Lett. 2007,
17, 6821; (h) Penthala, N. R.; Yerramreddy, T. R.; Crooks, P. A. Bioorg.
Med. Chem. Lett. 2010, 20, 591; (i) Vikas, S.; Pradeep, K.; Devender, P.
J. Heterocycl. Chem. 2010, 47, 491; (j) Kashyap, S. J.; Garg, V. K.;
Sharma, P. K.; Kumar, N.; Dudhe, R.; Gupta, J. K. Med. Chem. Res.
2012, 21, 2123; (k) Zhiwei, C.; Jianhao, B.; Weike, S. Chin. J. Chem.
2013, 31, 507; (l) Borges, F.; Roleira, F.; Milhazes, N.; Santana, L.;
Uriarte, E. Curr. Med. Chem. 2005, 12, 887.
2-(2-(2-((1H-Indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-3H-
benzo[f]chromen-3-one (7d): Yellowish green solid; Yield: 90%; mp:
-1
298-300 oC; IR (KBr, υmax cm ): 3383, 3247 (N-H), 1701 (C=O), 1631,
1604 (C=N), 1574 (C=C), 1100 (C-S); 1H NMR (400 MHz, DMSO-d6): δ
7.18-7.25 (m, 2H), 7.46 (d, J = 6.8 Hz, 1H), 7.63-7.69 (m, 2H), 7.81-
7.84 (m, 3H), 8.10 (d, J = 8.0 Hz, 1H), 8.20-8.39 (m, 4H), 9.31 (s, 1H),
11.56 (s, 1H), 11.91 (s, 1H); MS (ESI) m/z: 437 [M + H]+; HRMS for
C25H16N4O2S: Calcd. 436.0994; Found 436.0990; Anal. calcd. for: C,
68.79; H, 3.69; N, 12.84; Found: C, 68.81; H, 3.58; N, 12.68.
3-(2-(2-((1H-Indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-6-bromo-2H-
chromen-2-one (7e): Green solid; Yield: 89%; mp: 272-274 oC; IR (KBr,
4. (a) Arshad, A.; Osman, H.; Bagley, M. C.; Lam, C. K.; Mohamad, S.;
Zahariluddin, A. S. Eur. J. Med. Chem. 2011, 46, 3788; (b) Vijesh, A.
M.; Isloor, A. M.; Prabhu, V.; Ahmad, S.; Malladi, S. Eur. J. Med. Chem.
2010, 45, 5460.
-1
υmax cm ): 3164, 3049 (N-H), 1712 (C=O), 1632, 1603 (C=N), 1575
(C=C), 1067 (C-S), 693 (C-Br); 1H NMR (400 MHz, DMSO-d6, D2O
exchange): δ 7.20 (t, J = 8.0 Hz, 2H), 7.40-7.47 (m, 3H), 7.74 (t, J = 8.8
Hz, 2H), 8.07 (s, 1H), 8.20 (d, J = 7.2 Hz, 1H), 8.29 (s, 1H), 8.48 (s, 1H);
MS (ESI) m/z: 467 [M + 2]+; Anal. calcd. for C21H13BrN4O2S: C, 54.20;
H, 2.82; N, 12.04; Found: C, 54.28; H, 2.74, N, 12.21.
5. Ganem, B. Acc. Chem. Res. 2009, 42, 463.
6. (a) Franco, C.; Bruna, B.; Adriana, B.; Daniela, S.; Paola, C.; Arianna,
G.; Simone, C.; Melissa, D. A.; Maddalena, M. S.; Francesca, S. J.
Heterocycl. Chem. 2010, 47, 1269; (b) Chimenti, P.; Petzer,
A.; Carradori, S.; D'Ascenzio, M.; Silvestri, R.; Alcaro, S.; Ortuso,
F.; Petzer, J. P.; Secci, D. Eur. J. Med. Chem. 2013, 66, 221.
3-(2-(2-((1H-Indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-6,8-dibromo-
2H-chromen-2-one (7f): Green solid; Yield: 90%; mp: 285-287 oC; IR
(KBr, υmax cm-1): 3154 (N-H), 1737 (C=O), 1626, 1606 (C=N), 1574
(C=C), 1109 (C-S), 680 (C-Br); 1H NMR (400 MHz, DMSO-d6): δ 7.17-
7.24 (m, 2H), 7.45 (d, J = 7.6 Hz, 1H), 7.79 (t, J = 8.0 Hz, 2H), 8.11-8.23
(m, 3H), 8.30 (s, 1H), 8.45 (s, 1H), 11.53 (s, 1H), 11.96 (s, 1H); MS
(ESI) m/z: 545 [M + H]+; HRMS for C21H12Br2N4O2S: Calcd. 541.9048;
Found 541.9051; Anal. calcd. for: C, 46.35; H, 2.22; N, 10.29; Found: C,
46.48; H, 2.12, N, 10.42.
7. (a) Kuarm, B. S.; Reddy, Y. T.; Madhav, J. V.; Crooks, P. A.; Rajitha, B.
Bioorg. Med. Chem. Lett. 2011, 21, 524; (b) Laxmi, S. V.; Reddy, Y. T.;
Kuarm, B. S.; Reddy, P. N.; Crooks, P. A.; Rajitha, B. Bioorg. Med.
Chem. Lett. 2011, 21, 4329; (c) Janardhan, B. Rajitha, B. Chin. Chem.
Lett. 2012, 23, 1015; (d) Janardhan, B.; Ravibabu, V.; Rajitha, G.;
Rajitha, B.; Crooks, P. A. Tetrahedron Lett. 2013, 54, 3862.
8. General procedure for the synthesis of indole incorporated
6,8-Dibromo-3-(2-(2-((5-methoxy-1H-indol-3-yl)methylene)hydrazinyl)
thiazol-4-yl)-2H-chromen-2-one (7g): Green solid; Yield: 92%; mp: 266-
268 oC IR (KBr, υmax cm-1): 3417, 3271 (N-H), 1729 (C=O), 1633, 1603
(C=N), 1580 (C=C), 1104 (C-S), 606 (C-Br); 1H NMR (400 MHz,
DMSO-d6): δ 3.86 (s, 3H), 6.84-6.87 (d, J = 8.4 Hz, 1H ), 7.34 (d, J = 8.8
Hz, 1H), 7.73-7.81 (m, 3H), 8.12-8.17(m, 2H), 8.28 (s, 1H), 8.46 (s, 1H),
11.40 (s, 1H), 11.87 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 167.28,
158.06, 154.84, 148.49, 140.48, 136.59, 136.06, 132.29, 132.05, 130.67,
130.31, 129.00, 124.90, 122.50, 116.75, 113.18, 112.92, 111.76, 111.65,
110.16, 103.83, 55.69; MS (ESI) m/z: 575 [M + H]+; Anal. calcd. for
thiazolylcoumarins (7a-q): To
a
mixture of substituted indole-3-
mmol) and
carbaldehyde (5a-e, 1 mmol), thiosemicarbazide (6,
1
substituted 3-(2-bromoacetyl)-2H-chromen-2-ones (4a-d, 1 mmol)/2-(2-
bromoacetyl)-3H-benzo[f]chromen-3-one (4e, 1 mmol) in 10 mL ethanol,
catalytic amount of acetic acid was added and refluxed for 2-4 h. The
progress of the reaction was monitored by TLC. After completion of the
reaction, the solid separated out was filtered, washed with hot ethanol,
afforded analytically pure product without recrystallization.
Spectral data:
6
*Corresponding author: Tel: 0091-0870-2459445; Fax: 0091-0870-2459547
E-mail: rajitabhargavi@yahoo.com

C22H14Br2N4O3S: C, 46.01; H, 2.46; N, 9.76; Found: C, 46.20; H, 2.32,
N, 9.87.
466.1091; Anal. calcd. for: C, 66.94; H, 3.89; N, 12.01; Found: C, 66.81;
H, 3.75; N, 12.12.
3-(2-(2-((1-Ethyl-1H-indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-2H-
chromen-2-one (7h): Yellow solid; Yield: 85%; mp: 246-248 oC; IR
(KBr, υmax cm-1): 3439, 3282 (N-H), 1716 (C=O), 1603 (C=N), 1574
(C=C), 1097 (C-S); 1H NMR (400 MHz, DMSO-d6): δ 1.39 (t, J = 6.8
Hz, 3H), 4.22-4.27 (m, 2H), 7.20-7.29 (m, 2H), 7.40 (t, J = 7.6 Hz, 1H),
7.46 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 7.6 Hz, 1H), 7.61-7.76 (m, 1H),
7.76 (s, 1H), 7.86 (d, J = 8.4 Hz, 2H), 8.25 (t, J = 8.8 Hz, 2H), 8.56 (s,
1H), 11.86 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 167.93, 158.71,
152.26, 143.50, 139.63, 138.09, 136.60, 131.82, 131.61, 128.74, 124.67,
124.54, 122.60, 121.79, 120.68, 120.43, 119.16, 115.84, 110.74, 110.24,
6,8-Dibromo-3-(2-(2-((2-methyl-1H-indol-3-
yl)methylene)hydrazinyl)thiazol-4-yl)-2H-chromen-2-one (7n): Brown
solid; Yield: 85%; mp: 292-294 oC; IR (KBr, υmax cm-1): 3164, 3052 (N-
H), 1715 (C=O), 1626, 1607 (C=N), 1574 (C=C), 1104 (C-S), 699 (C-
Br); 1H NMR (400 MHz, DMSO-d6): δ 2.50 (s, 3H), 7.12-7.14 (m, 2H),
7.33 (t, J = 7.2 Hz, 1H), 7.80 (s, 1H), 8.10-8.13 (m, 2H), 8.17 (d, J = 6.8
Hz, 1H), 8.35 (s, 1H), 8.46 (s, 1H), 11.45 (s, 1H), 11.74 (s, 1H); 13C
NMR (100 MHz, DMSO-d6): δ 168.08, 157.64, 148.04, 143.41, 139.27,
138.92, 136.12, 135.67, 135.58, 130.26, 130.10, 125.14, 122.23, 122.11,
121.66, 120.51, 120.25, 116.31, 111.19, 110.86, 109.70, 11.48; MS (ESI)
m/z: 559 [M + H]+; Anal. calcd. for C22H14Br2N4O2S: C, 47.33; H, 2.53;
N, 10.04; Found: C, 47.24; H, 2.59; N, 10.21.
109.80, 40.56, 15.17; MS (ESI) m/z: 415 [M
+
H]+; HRMS for
C23H18N4O2S: Calcd. 414.1150; Found 414.1139; Anal. calcd. for: C,
66.65; H, 4.38; N, 13.52; Found: C, 66.54; H, 4.42, N, 13.39.
2-(2-(2-((1-Ethyl-1H-indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-3H-
benzo[f]chromen-3-one (7o): Green solid; Yield: 88%; mp: 295-297 oC;
IR (KBr, υmax cm-1): 3405, 3150 (N-H), 1713 (C=O), 1633, 1603 (C=N),
1570 (C=C), 1099 (C-S); 1H NMR (400 MHz, DMSO-d6): δ 1.40 (t, J =
7.2 Hz, 3H), 4.22-4.28 (m, 2H), 7.22-7.30 (m, 2H), 7.57 (d, J = 8 Hz,
1H), 7.66 (t, J = 8.8 Hz, 2H), 7.84 (t, J = 8.8 Hz, 3H), 8.11 (d, J = 8.4 Hz,
1H), 8.21-8.29 (m, 3H), 8.37 (d, J = 8.4 Hz, 1H), 9.32(s, 1H), 11.96 (s,
1H); 13C NMR (100 MHz, DMSO-d6): δ 167.99, 158.67, 151.85, 139.57,
136.61, 133.46, 132.81, 131.81, 130.02, 129.08, 128.66, 128.50, 126.09,
124.54, 122.59, 121.79, 121.46, 120.67, 116.42, 113.15, 110.75, 110.24,
6-Bromo-3-(2-(2-((2-methyl-1H-indol-3-yl)methylene)hydrazinyl)thiazol-
4-yl)-2H-chromen-2-one (7i): Green solid; Yield: 84%; mp: 276-278 oC;
IR (KBr, υmax cm-1): 3488, 3234 (N-H), 1738 (C=O), 1638, 1600 (C=N),
1552 (C=C), 1105 (C-S), 664 (C-Br); 1H NMR (400 MHz, DMSO-d6): δ
2.73 (s, 3H), 7.12 (s, 1H), 7.33 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.4 Hz,
1H), 7.76 (t, J = 8.4 Hz, 1H), 7.95 (s, 1H), 8.13 (t, J = 6.8 Hz, 2H), 8.36
(s, 1H), 8.50 (s, 1H), 11.45 (s, 1H), 11.58 (s, 1H); 13C NMR (100 MHz,
DMSO-d6): δ 168.00, 158.27, 152.03, 141.18, 141.01, 140.52, 139.59,
136.63, 135.69, 133.78, 130.61, 125.14, 121.36, 121.18, 120.52, 120.29,
118.06, 116.32, 111.09, 110.89, 11.49; MS (ESI) m/z: 481 [M + 2]+;
Anal. calcd. for C22H15BrN4O2S: C, 55.12; H, 3.15; N, 11.69; Found: C,
55.23; H, 3.27, N, 11.48.
109.77, 40.55, 15.16; MS (ESI) m/z: 465 [M
+
H]+; HRMS for
C27H20N4O2S: Calcd. 464.1307; Found 464.1304; Anal. calcd. for: C,
69.81; H, 4.34; N, 12.06; Found: C, 69.74; H, 4.39; N, 12.11.
6,8-Dibromo-3-(2-(2-((1-ethyl-1H-indol-3-
3-(2-(2-((5-Bromo-1H-indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-2H-
chromen-2-one (7p): Brown solid; Yield: 90%; mp: 301-303 oC; IR
(KBr, υmax cm-1): 3337, 3269 (N-H), 1736, 1698 (C=O), 1621, 1603
(C=N), 1579 (C=C), 1108 (C-S); 1H NMR (400 MHz, DMSO-d6): δ
7.33-7.48 (m, 4H), 7.64 (t, J = 7.6 Hz, 1H), 7.79 (s, 1H), 7.85 (t, J = 6.8
Hz, 2H) , 8.27 (s, 1H), 8.38 (s, 1H), 8.56 (s, 1H), 11.72 (s, 1H), 11.91 (s,
1H); MS (ESI) m/z: 466 [M + H]+; Anal. calcd. for C21H13BrN4O2S: C,
54.20; H, 2.82; N, 12.04; Found: C, 54.29; H, 2.78; N, 12.18.
yl)methylene)hydrazinyl)thiazol-4-yl)-2H-chromen-2-one (7j): Brown
solid; Yield: 87%; mp: 260-262 oC IR (KBr, υmax cm-1): 3488, 3234 (N-
H), 1738 (C=O), 1638, 1600 (C=N), 1552 (C=C), 1105 (C-S), 664 (C-
Br); 1H NMR (400 MHz, DMSO-d6): δ 1.39 (t, J = 7.6 Hz, 3H), 4.22-
4.27 (m, 2H), 7.20-7.29 (m, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.83 (d, J =
8.8 Hz, 2H), 8.12-8.28 (m, 4H), 8.46 (s, 1H), 11.86 (s, 1H); MS (ESI)
m/z: 573 [M + H]+; Anal. calcd. for C23H16Br2N4O2S: C, 48.27; H, 2.82;
N, 9.79; Found: C, 48.07; H, 2.94; N, 9.68.
6-Chloro-3-(2-(2-((2-methyl-1H-indol-3-yl)methylene)hydrazinyl)thiazol-
4-yl)-2H-chromen-2-one (7q): Green solid; Yield: 93%; mp: 279-281 oC;
IR (KBr, υmax cm-1): 3262, 3154 (N-H), 1716 (C=O), 1630, 1604 (C=N),
1579 (C=C), 1101 (C-S), 782 (C-Cl); 1H NMR (400 MHz, DMSO-d6): δ
2.50 (s, 3H), 7.13 (t, J = 7.2 Hz, 2H), 7.35 (t, J = 6.8 Hz, 1H), 7.49 (d, J
= 8.8 Hz, 1H), 7.63-7.66 (m, 1H),7.79 (s, 1H), 8.03 (s, 1H), 8.11 (t, J =
7.2 Hz, 1H), 8.35 (s, 1H), 8.51 (s, 1H), 11.45 (s, 1H), 11.75 (s, 1H); 13C
NMR (100 MHz, DMSO-d6): δ 168.02, 158.32, 150.82, 139.30, 138.94,
136.64, 135.67, 130.97, 128.43, 127.66, 125.13, 121.67, 120.50, 120.26,
117.77, 110.87, 110.56, 107.25, 11.46; MS (ESI) m/z: 435 [M + H]+;
Anal. calcd. for C22H15ClN4O2S: C, 60.76; H, 3.48; N, 12.88; Found: C,
60.80; H, 3.40; N, 12.79.
6-Bromo-3-(2-(2-((1-ethyl-1H-indol-3-yl)methylene)hydrazinyl)thiazol-4-
yl)-2H-chromen-2-one (7k): Green solid; Yield: 86%; mp: 250-252 oC; IR
-1
(KBr, υmax cm ): 3392, 3025 (N-H), 1726 (C=O), 1634, 1602 (C=N),
1572 (C=C), 1097 (C-S), 694 (C-Br); 1H NMR (400 MHz, DMSO-d6): δ
1.39 (t, J = 7.6 Hz, 3H), 4.21-4.25 (m, 2H), 7.22-7.27 (m, 2H), 7.43 (d, J
= 8.8 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.75-7.79 (m, 2H), 7.85 (s, 1H),
8.14-8.27 (m, 3H), 8.49 (s, 1H), 11.86 (s, 1H); MS (ESI) m/z: 494 [M +
H]+; Anal. calcd. for C23H17BrN4O2S: C, 55.99; H, 3.47; N, 11.36;
Found: C, 55.90; H, 3.54; N, 11.49.
3-(2-(2-((1H-Indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-6-chloro-2H-
chromen-2-one (7l): Yellow solid; Yield: 95%; mp: 258-260 oC; IR (KBr,
-1
υmax cm ): 3429, 3117 (N-H), 1707 (C=O), 1633, 1606 (C=N), 1574
9. (a) Smith, G. F. J. Chem. Soc. 1954, 3842; (b) Sahu, S. K.; Mishra, A.;
Behera, R. K. Indian J. Heterocycl. Chem. 1996, 6, 91.
(C=C), 1078 (C-S), 743 (C-Cl); 1H NMR (400 MHz, DMSO-d6): δ 7.20
(t, J = 7.2 Hz, 2H), 7.45-7.51 (m, 2H), 7.66 (t, J = 7.2 Hz, 2H), 7.80 (s,
1H), 8.01 (s, 1H), 8.22 (d, J = 7.6 Hz, 1H), 8.30 (s, 1H), 8.51 (s, 1H),
11.53 (s, 1H), 11.85 (s, 1H); 13C NMR (100 MHz, DMSO-d6): δ 168.56,
158.81, 151.31, 144.10, 140.36, 137.53, 137.10, 131.48, 130.15, 128.93,
128.13, 124.45, 123.03, 122.07, 121.18, 120.92, 118.29, 112.34, 111.97,
111.17, 110.00; MS (ESI) m/z: 421 [M + H]+; HRMS for C21H13ClN4O2S:
Calcd. 420.0448, Found 420.0452; Anal. calcd. for: C, 59.93; H, 3.11; N,
13.31; Found: C, 59.81; H, 3.20; N, 13.24.
10. Seelay, H. W.; Van Demark, P. J. Microbes in action: A laboratory
manualin microbiology, 2nd ed. D. B. Taraporevala Sons & Co. Pvt.,
Bombay, India. 1975, 55.
11. (a) Alley, M. C.; Scudiero, D. A.; Monks, A.; Hursey, M. L.; Czerwinski,
M. J.; Fine, D. L.; Abbott, B. J.; Mayo, J. G.; Shoemaker, R. H.; Boyd,
M. R. Cancer Res. 1988, 48, 589; (b) Boyd, M. R.; Paull, K. D. Drug
Dev. Res. 1995, 34, 91; (c) Penthala, N. R.; Yerramreddy, T. R.; Crooks,
P. A. Bioorg. Med. Chem. Lett. 2011, 21, 1411; (d) Kattimani, P. P.;
Kamble, R. R.; Kariduraganavar, M. Y.; Dorababu, A.; Hunnur, R. K.
Eur. J. Med. Chem. 2013, 62, 232.
2-(2-(2-((5-Methoxy-1H-indol-3-yl)methylene)hydrazinyl)thiazol-4-yl)-
3H-benzo[f]chromen-3-one (7m): Green solid; Yield: 89%; mp: 281-283
oC; IR (KBr, υmax cm-1): 3176, 3062 (N-H), 1725, 1701 (C=O), 1640,
1602 (C=N), 1577 (C=C), 1104 (C-S); 1H NMR (400 MHz, DMSO-d6):
δ 3.88 (s, 3H), 6.85-6.88 (m, 1H), 7.35 (d, J = 8.8 Hz, 1H), 7.66 (t, J =
8.8 Hz, 2H), 7.74 (d, J = 6.8 Hz, 1H), 7.80-7.84 (m, 3H), 8.10 (d, J = 8.4
Hz, 1H), 8.21 (d, J = 8.8 Hz, 1H), 8.30 (s, 1H), 8.37 (d, J = 8.8 Hz, 1H),
9.32 (s, 1H), 11.41 (s, 1H), 11.94 (s, 1H); 13C NMR (100 MHz, DMSO-
d6): δ 168.12, 158.66, 154.45, 151.87, 140.33, 133.54, 132.86, 131.90,
130.06, 130.02, 129.08, 128.67, 128.50, 126.11, 124.52, 121.50, 119.43,
116.41, 113.14, 112.53, 112.44, 111.22, 109.78, 103.48, 55.28; MS (ESI)
m/z: 467 [M + H]+; HRMS for C26H18N4O3S: Calcd. 466.1100; Found
12. Zaharevitz, D. W.; Holbeck, S. L.; Bowerman, C.; Svetlik, P. A. J. Mol.
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*Corresponding author: Tel: 0091-0870-2459445; Fax: 0091-0870-2459547
E-mail: rajitabhargavi@yahoo.com