4-Aryl-4H-Chromene-3-Carbonitrile Derivates: Synthesis and Preliminary Anti-Breast Cancer Studies

Article abstract of DOI:10.1002/jhet.2483

A series of new 4-aryl-4H-chromene-3-carbonitrile derivatives were obtained by one-pot synthesis using substituted benzaldehydes, malononitrile, and substituted phenols. All the synthesized compounds (1a, 1b, 1c, 1d, 1e) were screened in vitro for antioxi

Full text of DOI:10.1002/jhet.2483

Month 2015 4-Aryl-4H-Chromene-3-Carbonitrile Derivates: Synthesis and Preliminary
Anti-Breast Cancer Studies
Nancy Thomas, Subin Mary Zachariah, and Prasanna Ramani
a
a
b
*
aDepartment of Pharmaceutical Chemistry, Amrita School of Pharmacy, AIMS Campus, Amrita Vishwa Vidyapeetham,
Kochi, 682041, India
bCenter of Excellence in Advanced Materials and Green Technologies, Dhanvanthri Lab, Department of Sciences, Amrita
Vishwa Vidyapeetham, Amrita Nagar, Coimbatore, 641112, India
*
E-mail: r_prasanna1@cb.amrirta.edu
Additional Supporting Information may be found in the online version of this article.
Received March 27, 2015
DOI 10.1002/jhet.2483
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
A series of new 4-aryl-4H-chromene-3-carbonitrile derivatives were obtained by one-pot synthesis using
substituted benzaldehydes, malononitrile, and substituted phenols. All the synthesized compounds (1a–e)
were screened in vitro for antioxidant and anticancer activities. Compounds 1c–e showed significant antiox-
idant activity in nitric oxide free radical scavenging method while compounds 1c and 1e showed significant
activity in hydrogen peroxide free radical scavenging method. The other compounds showed significant to
moderate activities in both the methods in comparison with ascorbic acid and butylated hydroxytoluene as
standards. Compounds 1c–e exhibited good anticancer activity, using Michigan Cancer Foundation-7
(MCF-7) cell line, compared with those of other synthesized compounds.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
describes a simple and efficient one-pot synthesis of chromene
derivatives (Scheme 1) followed by the results of preliminary
in vitro screening for anticancer activities.
Chromene and its derivatives are widely present in
plants/fruits that possess a broad range of biological activity
[1,2] and identified as one of the potential anticancer agent
[3,4]. Among different types of chromene systems,
2-amino-4H-chromenes are of particular utility as they be-
longs to privileged medicinal scaffolds serving for generation
of small-molecule ligands with highly pronounced anticoagu-
lant, diuretic, spasmolytic, antianaphylactic, antimicrobial,
antiviral, mutagenicity, and antiproliferative activities [5–11].
Several procedures for the synthesis of 2-amino-4H-pyrans
have been described [12–16]. Many catalysts such as piperi-
dine [17], morpholine [18], cetyltrimethylammonium chloride
[19], triethylbenzylammonium chloride [20] and alumina [21]
have been used for this reaction, but all these methods require
a long duration and suffer from lack of general applicability. A
multi-component reaction finds special place in synthetic
strategy for rapid and efficient library generation. This article
CHEMISTRY
In a previous study [2], it was shown that in silico target
profiling was able to identify the targets at which a chemical
library of biological molecules should be tested, leading to
the identification of new molecules for tubulin, estrogen recep-
tor, and Tumor necrosis factors (TNF)-α receptor containing a
chromene scaffold. The synthetic pathway to obtain com-
pounds namely 4-Aryl-4H-chromene-3-carbonitrile derivates
1 is outlined in Scheme 1.
One-pot synthesis of 4-aryl-4H-chromenes 1a–e was per-
formed by using malononitrile 3, substituted benzaldehydes
2, and substituted phenols 4. The reaction mixture was
heated at 60–80°C for 3h in ethanol using catalytic quantities
© 2015 HeteroCorporation

N. Thomas, S. M. Zachariah, and P. Ramani
Vol 000
Scheme 1. Synthesis of compounds 1a–e.
of piperidine. The completion of reaction was monitored
using thin-layer chromatography (TLC); precipitate formed
was filtered and washed with cold ethanol–water mixture.
The crude product was crystallized from ethanol to get corre-
sponding chromene analogue in good yield (Table 1). The
compounds 1a–e were characterized by 1H-NMR, 13C-
NMR, IR, and mass spectra, and the data were found to be
in good agreement with the proposed structures. All the phe-
nols employed in the present work are 3-substituted which
could in principle cyclise through position 2 or 6. The regio-
selective cyclisation at position 6 is most likely due to the
hindrance at position 2 of the 3-substituted phenols.
The plausible mechanism of one-pot synthesis involves
three steps, namely Knoevenagel condensation, Michael
addition followed by intramolecular cyclisation of the
Michael adduct, as shown in Scheme 2.
RESULTS AND DISCUSSION
Biological study. Antioxidant studies. The main feature
of an antioxidant was its ability to trap free radicals. These free
radicals may oxidize nucleic acids, proteins, lipids, or DNA
and can initiate degenerative disease. Antioxidant
compounds scavenge free radicals such as peroxide,
hydroperoxide, or lipid peroxyl and thus inhibit the oxidative
mechanisms. In this study, in vitro antioxidant activity of all
the synthesized compounds was assessed by nitric oxide and
hydrogen peroxide free radical scavenging methods using
ascorbic acid and butylated hydroxytoluene as references.
The nitric oxide scavenging method is based on the gener-
ation of nitric oxide (NO) from sodium nitroprusside. The
NO generated reacts with oxygen to produce nitrite ions,
which are frequently inhibited by antioxidants or nitric oxide
scavengers. The quantity of NO generated will be less when
sodium nitroprusside is incubated in the presence of antioxi-
dants such as chromenes, which are used in this study. The
excess NO is estimated through Griess reagent.
Table 1
One-pot synthesis of malonitrile, substituted benzaldehyde, and
substituted phenol for the preparation of 4-Aryl-4H-chromene-3-
carbonitrile derivatives 1a.
Product 1b
R and R′
Yieldc (%)
Mp (°C)
a
b
c
d
e
OH and Br
OH and F
OCH3 and Br
OCH3 and Cl
OCH3 and F
85
80
70
70
73
108–110
176–178
115–116
162–164
134–136
aAll reactions were run with corresponding substituted phenol, aldehyde,
and malononitrile in ethanolic medium
bAs per Scheme 1.
Excess concentration of nitric oxide implicates cytotoxic
effects observed in various disorders such as cancer,
cThe yield of the reaction is based on substituted phenol.
Scheme 2. Plausible mechanism of the reaction.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
4-Aryl-4H-Chromene
Alzheimer’s, arthritis, and tissue damage. The nitric oxide free
radical can react with superoxide to form the peroxynitrite
anion, which is a potential oxidant that can decompose to
produce hydroxyl radicals and nitric oxide radicals.
The results presented in Table 2 reveal that 4-aryl-4H-
chromene-3-carbonitrile analogues exhibit effective anti-
oxidant activity compared with references. Out of these
compounds, 1c–e were found to be potent than other mol-
ecules. The IC50 values of 1e (IC50 30.0 μg/mL) exhibited
higher nitric oxide scavenging activity when compared
converted into singlet oxygen (O2) and hydroxy radicals,
which is a powerful oxidizing agent. Although H2O2 itself
is not very reactive, it can sometimes be toxic to a cell be-
cause it may give rise to hydroxyl radicals in the cells.
Cytotoxicity studies [22]. The in vitro anticancer screening
of all the prepared compounds was carried out by 3-[4,5-
dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide
(MTT) assay in MCF-7 cell lines. The MTT assay is based
on the hypothesis that living cells reduce tetrazolium due to
the presence of mitochondrial Succinate dehydrogenase
(SDH), which is absent in the metabolically inactive dead
cells. This assay therefore depends on both the number of
viable cells present and mitochondrial activity per cell.
Compounds 1a–e were evaluated for their in vitro cyto-
toxicity toward human estrogen receptor-positive breast
adenocarcinoma MCF-7 cell line. Cytotoxic activity was
evaluated by using the standard MTT assay, after exposure
of cells to the tested compounds for 72h (Table 4). Con-
centration of test drug needed to inhibit cell growth of
50% (CTC50) is obtained from the dose–response curves
for MCF-7 cell line. All the compounds were screened
for their cytotoxicity at different concentrations of 1000,
500, 250, 125, and 62.5 μg/mL. It is evident from results
that all the tested compounds displayed potent to moderate
growth inhibitory activity against MCF-7 cell line. The
with other molecules and standard ascorbic acid (IC50
=
20.6μg/mL). The compounds 1a and 1b show moderate
to good inhibition activity compared with the standard.
Scavenging of hydrogen peroxide by compounds 1a–e
may be attributed to their radical scavenging activity, by
which they can donate electrons to H2O2, thus reducing it
to water. The analysis revealed that all the compounds exhib-
ited significant antioxidant properties (Table 3). From the re-
sults of hydrogen peroxide scavenging activity, it is observed
that maximum scavenging activity was exhibited by 1c
(IC50 =26.8μg/mL) and 1e (IC50 =24.2μg/mL) when com-
pared with standard ascorbic acid (IC50 =24.8μg/mL).
Hydrogen peroxide is highly important because of its ability
to penetrate biological membranes and may oxidize a num-
ber of compounds. Hydrogen peroxide molecule gets
Table 2
Nitric oxide scavenging activity.
Percentage inhibition SEM (μg/mL)
30
Compound code
10
20
40
50
1a
1b
1c
1d
29.60 0.1822
22.80 0.0897
30.30 0.2000
28.51 0.1468
25.45 0.0775
31.75 0.1444
34.77 0.0533
42.06 0.0431
35.56 0.0777
46.18 0.1400
45.41 0.1415
39.38 0.1035
38.55 0.0888
50.53 0.0555
53.47 0.1288
48.30 0.2364
59.41 0.1324
54.28 0.1888
48.61 0.1142
49.65 0.0466
68.47 0.0666
66.61 0.1111
59.36 0.1026
67.42 0.0637
68.63 0.1415
61.57 0.1111
58.40 0.4800
77.82 0.0466
75.37 0.1866
68.25 0.1680
76.67 0.0944
74.68 0.1095
70.65 0.1184
66.28 0.0644
89.55 0.1755
1e
BHT
Ascorbic acid
SEM, standard error of the mean; BHT, butylated hydroxytoluene.
Table 3
Hydrogen peroxide scavenging activity.
Percentage inhibition SEM (μg/mL)
Compound code
10
20
30
40
50
1a
1b
1c
1d
29.35 0.1900
23.64 0.0622
26.44 0.0764
28.21 0.0464
27.26 0.0511
29.85 0.0822
26.89 0.0488
44.55 0.0497
37.26 0.0755
41.75 0.0422
43.65 0.0484
46.46 0.0820
37.86 0.0533
41.25 0.0622
56.37 0.1706
49.14 0.0586
53.61 0.2142
54.57 0.0846
55.45 0.0888
48.44 0.0768
56.76 0.2333
68.35 0.1417
60.83 0.0533
66.45 0.0564
67.33 0.0555
63.69 0.0697
59.35 0.0888
68.83 0.0377
76.46 0.1835
70.84 0.0444
74.55 0.0471
75.47 0.0826
74.83 0.0833
68.14 0.0806
86.72 0.0666
1e
BHT
Ascorbic acid
SEM, standard error of the mean; BHT, butylated hydroxytoluene.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

N. Thomas, S. M. Zachariah, and P. Ramani
Vol 000
Table 4
of these compounds indicate that they are good candi-
dates for further pharmacological studies toward discov-
ering effective chemotherapeutic agents for the
treatment of human cancer diseases.
Percentage inhibition of the compounds on MCF-7 cell lines.
Test
concentrations
Percentage
cytotoxicity
CTC50
(μg/mL)
Compounds
(μg/mL)
EXPERIMENTAL
1a
1000
500
250
88.16 0.3
86.44 0.5
82.12 0.6
74.96 0.4
50.50 0.3
77.43 0.3
75.12 0.5
58.58 0.4
52.99 0.3
34.64 0.6
89.31 0.2
87.02 0.4
75.93 0.3
73.50 0.2
71.75 0.3
87.95 0.2
79.36 0.3
78.04 0.4
73.61 0.3
71.10 0.3
87.88 0.4
85.91 0.2
77.65 0.5
75.54 0.4
55.19 0.5
Chemistry. General. All the chemicals used for the
reactions were purchased from Sigma-Aldrich (Bangalore,
India) or Loba Chemie Pvt Ltd. (Mumbai, India) unless
otherwise indicated. All the reactions were performed
under nitrogen/argon atmosphere. The reactions were
monitored by TLC, carried out on Silica gel G60 with
detection by UV or staining in an iodine chamber. NMR
(1H and 13C) spectra were recorded on a Bruker AXS
(400MHz) instrument. IR spectra were recorded on
Shimadzu Fourier transform infrared spectrophotometer.
Melting points were measured with Roy Capillary melting
point apparatus using open capillary tubes and are
uncorrected. Mass data were obtained by using Waters
2695–3100 LC/MS equipped with an electrospray
62.67 0.30
118.00 2.00
<62.5
125
62.5
1000
500
250
125
62.5
1000
500
250
125
62.5
1000
500
250
125
62.5
1000
500
250
125
1b
1c
1d
1e
<62.5
ionization (ESI) source.
General procedure for the synthesis of compounds
(1a–e). Two drops of piperidine were added to a mixture
<62.5
of substituted benzaldehyde (1 mmol), malononitrile
(1 mmol), and substituted phenol (1 mmol) in ethanol
(3 mL) at room temperature. The reaction mixture was
heated to 60–80 °C and stirred for 3 h. The reaction was
monitored by TLC (hexane : ethyl acetate = 7:3); after the
completion of reaction, cooled to room temperature, the
precipitate formed was filtered and washed with cold
ethanol containing trace of water. The crude product
was re-crystallized from ethanol to obtain the desired
62.5
analogues 1c, 1d, and 1e were found to be more potent,
when compared with others, against MCF-7 cell lines with
CTC50 less than 62.5 μg/mL.
The results highlighted that the presence of electron-
donating methoxy group at position 7 increases the
cytotoxic activity. Besides, presence of halogen at posi-
tion 3′ imparted the cytotoxic effect in the compounds.
Our findings are in agreement with other research
groups who emphasized the importance of halogen
substitution at 3′ position on chromene derivatives
[23–25]. The compounds 1a and 1b have demonstrated
anticancer activity with CTC50 values of 62.67 and
118.00 μg/mL, which are found to be less active than
other compounds.
molecules 1a–e.
2-Amino-3-cyano-4-(3′-bromophenyl)-7-hydroxy-4H-chromene
(1a). White crystalline solid. IR (KBr, νmax, cmꢀ1): 3444
(–OH), 3348 and 3585 (NH2), 3070 (arom. –CH), 2191
(CN), 1510 (C¼C), 1311 (C–N), 572 (C–Br). 1H-NMR
(DMSO-d6, 400 MHz): δH 9.78 (s, 1H, OH), 7.41 (d,
J=8Hz, 1H, H-4′), 7.34 (s, 1H, H-2′), 7.28 (t, J=8 Hz, 1H,
H5′), 7.18 (d, J= 8Hz, 1H, H-6′), 6.99 (s, 2H, –NH2), 6.82
(d, J=8.4Hz, 1H, H–Ar), 6.50 (dd, J= 2.4, 8.8 Hz, 1H,
H–Ar), 6.41 (d, J= 2.4 Hz, 1H, H–Ar), 4.67 (s, 1H, H-4).
13C-NMR (DMSO-d6, 400MHz): δC 160.33, 157.28,
149.09, 148.79, 130.90, 129.94, 129.87, 129.57, 126.56,
121.80, 120.43, 112.94, 112.51, 102.24, 55.99, 45.60. MS
CONCLUSION
We described a convenient route to the synthesis of 4-aryl-
4H-chromenes in good yields. From the biological screening,
it was observed that the presence of electron-donating
methoxy groups at position 7 and electronegative
halogens at position 3′ of 4-aryl-4H-chromene moiety
improves the antioxidant and anticancer activity of the
compounds. Molecules 1c, 1d, and 1e showed good
antioxidant and anticancer activities compared with
other compounds of the present study. Cytotoxic effects
(ESI): 365 (M + Na), 343 (M + H).
2-Amino-3-cyano-(3′-fluorophenyl)-7-hydroxy-4H-chromene
(1b). Yellow crystalline solid. IR (KBr, νmax, cmꢀ1): 3442
(O–H), 3375 and 3217 (NH2), 3088 (arom. –CH), 2193
(CN), 1500 (C¼C), 1313 (C–N), 1047 (C–F str.). 1H-NMR
(DMSO-d6, 400MHz): δH 9.74 (s, 1H, OH), 7.06–6.96 (m,
4H, o-, m-, & p- to F), 6.93 (s, 2H, NH2), 6.83–6.41 (m,
3H, Ar–H), 4.69 (s, 1H, H-4). 13C-NMR (DMSO-d6,
400MHz): δC 163.43, 160.34, 157.23, 149.27, 148.81,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
4-Aryl-4H-Chromene
REFERENCES AND NOTES
130.61, 130.52, 123.44, 120.45, 114.09, 113.34, 113.05,
112.45, 102.02, 55.99, 45.66; MS (ESI): 283 (M+H).
2-Amino-3-cyano-(3′-bromophenyl)-7-methoxy-4H-chromene
(1c). Yellow crystalline solid. IR (KBr, νmax, cmꢀ1): 3423
[1] Filipe, A.; Marta, C.; Marián, C.; José, B.; Elisabet, G.-P.;
Fernanda, P.; Jordi, M.; María, I. L. Eur J Med Chem 2012, 54, 303.
[2] Nancy, T.; Subin, M. Z. Int J Pharm Sci Rev Res 2013, 22, 50.
[3] Shiva Kumar, K.; Rambabu, D.; Bagineni, P.; Mohammad, M.;
Rama Krishna, G.; Basaveswara Rao, M. V. Org Biomol Chem 2012, 10,
4774.
[4] Manal Kandeel, M.; Aliaa Kamal, M.; Eman Abdelall, K. A.;
Heba Elshemy, A. H. Eur J Med Chem 2013, 59, 183.
[5] Safari, J.; Banitaba, S. H.; Khalili, S. D. J. Mol Catal A: Chem
2011, 335, 46.
[6] Li, Y. L.; Chen, H.; Shi, C. L.; Shi, D. Q.; Ji, S. J. J Comb
Chem 2010, 12, 231.
[7] Shi, D. Q.; Chen, J.; Zhuang, Q. Y.; Hu, W. W. J Chem Res
2003, 30, 674.
[8] Patchett, A. A.; Nargund, R. P. Annu Rep Med Chem 2000,
35, 289.
and 3360 (NH2), 3064 (arom. –CH), 2193 (CN), 1506
1
(C¼C), 1290 (C–N), 1147 (C–O), 580 (C–Br). H-NMR
(DMSO-d6, 400MHz): δH 7.43 (d, J= 7.6 Hz, 1H, H-4′),
7.36 (s, 1H, H-2′), 7.29 (t, J= 8 Hz, 1H, H-5′), 7.19 (d,
J= 7.6Hz, 1H, H-6′), 7.01 (s, 2H, NH2), 6.95 (d, J=8.4Hz,
1H, Ar–H), 6.68 (dd, J= 8.4 Hz, 1H, Ar–H), 6.57 (d,
J=2.4Hz, 1H, Ar–H), 4.74 (s, 1H, H-4), 3.73 (s, 3H, OCH3).
13C-NMR (DMSO-d6, 400MHz): δC 160.28, 159.04, 149.09,
148.89, 133.07, 130.94, 129.96, 129.66, 126.56, 121.84,
120.33, 114.61, 111.43, 100.98, 55.57, 55.37, 45.53. MS
[9] Bonsignore, L.; Loy, G.; Secci, D.; Calignano, A. Eur J Med
Chem 1993, 28, 517.
[10] Bhat, M. A.; Siddiqui, N.; Khan, S. A. Acta Pol Pharm 2008,
65, 235.
(ESI): 379 (M + Na), 357 (M + H), 201 (M + 2Na).
2-Amino-3-cyano-(3′-chlorophenyl)-7-methoxy-4H-chromene
(1d). Yellow crystalline solid. IR (KBr, νmax, cmꢀ1): 3441
and 3370 (NH2), 3053 (arom. –CH str.), 2191 (CN), 1506
(C¼C), 1294 (CN), 1128 (C–O), 785 (C–Cl). 1H-NMR
(DMSO-d6, 400MHz): δH 7.35 (d, J=7.6Hz, 1H, H-4′),
7.29 (s, 1H, H-2′), 7.22 (t, J=8Hz, 1H, H-5′), 7.15 (d,
J=8 Hz, 1H, H-6′), 7.0 (s, 2H, NH2), 6.95 (d, J=8.8Hz,
1H, Ar–H), 6.68 (dd, J=2.4, 8.4Hz, 1H, Ar–H), 6.57 (d,
J=2.4Hz, 1H, Ar–H), 4.75 (s, 1H, H-4), 3.74 (s, 3H,
OCH3). 13C-NMR (DMSO-d6, 400MHz): δC 160.29,
159.04, 148.88, 148.63, 133.15, 130.62, 129.93, 127.10,
126.76, 126.16, 120.32, 114.61, 111.42, 100.98, 55.57,
[11] Skommer, J.; Wlodkowic, D.; Matto, M.; Eray, M. Pelkonen J
Leukemia Res 2006, 30, 322.
[12] Gourdeau, H.; Leblond, L.; Hamelin, B.; Desputeau, C.; Dong, K.;
Kianicka, I.; Custeau, D.; Bourdeau, C.; Geerts, L.; Cai, S.; Drewe, X. J.;
Labrecque, D.; Kasibhatla, S.; Tseng, B. Mol Cancer Ther 2004, 3, 1375.
[13] Cheng, J. F.; Akira, I.; Yoshinori, O.; Thomas, A.; Alex, N.
Bioorg Med Chem Lett 2003, 13, 3647.
[14] Kabalka, G. W.; Venkataiah, B.; Das, B. C. Synlett 2004, 2004,
2194.
[15] Makarem, S.; Mohammadi, A. A.; Fakhari, A. R. Tetrahedron
Lett 2008, 49, 7194.
[16] Shaabani, A.; Ghadari, R.; Ghasemi, S.; Pedarpour, M.;
Rezayan, A. H.; Sarvary, A. W.; Ng, S. J. Comb Chem 2009, 11, 956.
[17] Chetan, B. S.; Nimesh, M. S.; Manish, P. P.; Ranjan, G. P.
J Serb Chem Soc 2012, 77, 1.
55.37, 45.50. MS (ESI): 313 (M+H)+.
2-Amino-3-cyano-(3′-fluorophenyl)-7-methoxy-4H-chromene
(1e).
Pinkish yellow crystalline solid. IR (KBr, νmax,
[18] Ruth, D.; David, S. C. B.; Vanida, C.; Rohan, A. D.; Naresh, K.
Bioorg Med Chem 2012, 20, 1527.
cmꢀ1): 3437 and 3382 (NH2), 3053 (arom. –CH str.),
2189 (CN), 1455 (C¼C), 1296 (C–N), 1126 (C–O), 1045
[19] Bhagya, B.; Ramakrishna, A. NUJHS 2012, 2, 2.
[20] Odedire, O. O.; Olaleye, M. T.; Adekunle, A. S.; Ehigie, L. O.;
Olabinri, P. F. Research Journal of Biological Sciences 2010, 5, 102.
[21] Serhat, K.; Sait, C.; Semra, T.; Okkes, Y.; Ismail, T. Chemistry
Journal 2012, 2, 9.
[22] Francis, D.; Rita, L. J Immunol Methods 1986, 89, 271.
[23] Abdou, I. M.; Saleh, A. M.; Zohdi, H. F. Molecules 2004, 9,
109.
1
(CF). H-NMR (DMSO-d6, 400MHz): δH 7.07–6.95 (m,
4H, o-, m-, & p- to F), 6.99 (s, 2H, NH2), 6.69–6.56 (m,
3H, Ar–H), 4.75 (s, 1H, H-4), 3.74 (s, 3H, –OCH3). 13C-
NMR (DMSO-d6, 400MHz): δC 163.44, 161.01, 160.29,
159.02, 149.00, 148.88, 130.68, 129.91, 123.46, 120.35,
114.70, 113.43, 111.36, 100.96, 55.60, 55.40, 45.67. MS
(ESI): 295 (Mꢀ H).
[24] Mortimer, C. G.; Wells, G.; Crochard, J. P.; Stone, E. L.;
Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. J Med Chem
2006, 49, 179.
[25] Sathianarayanan, Amrutha
B
Chittethu, Asha Jose,
Ranganathan Balasubramanian; Saranya T. S.; Asha Asokan Manakadan;
Prasanna Ramani 2015, Design and Synthesis of Isatin Semicarbazone
Derivatives Against Mammary Carcinoma Cells, Medicinal Chemistry
Research, Accepted.
Acknowledgment. The authors would like to thank the ‘Kerala
State Council for Science, Technology and Environment’ for
their partial financial support to carry out this project.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet