Investigation of anticancer potencies of newly generated Schiff base imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines

Article abstract of DOI:10.1016/j.cclet.2016.10.021

A new series of multi-heterocyclic Schiff base was constructed starting from 4′-(imidazol-1-yl)-acetophenone which was converted to its 2-bromoethanone precursor which on cyclic condensation with thiourea yielded final thiazol-2-amine intermediate (3) to

Full text of DOI:10.1016/j.cclet.2016.10.021

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Chinese Chemical Letters xxx (2016) xxx–xxx
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Chinese Chemical Letters
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Original article
Investigation of anticancer potencies of newly generated Schiff base
imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines
Nikhil M. Parekha,1, Bhupendra M. Mistryb,1, Muthuraman Panduranganb,
Surendra K. Shindec, Rahul V. Pateld,
*
a
Department of Mathematics, Science & Humanities, Shroff S. R. Rotary Institute of Chemical Technology, Valia 393 135, India
Organic Research Laboratory, Department of Bioresources and Food Science, College of Life and Environmental Sciences, Konkuk University, Seoul 143 701,
b
Republic of Korea
c
College of Life Science and Biotechnology, Department of Biological and Environmental Science, Dongguk University, 32, Ilsandong-gu, Goyang-si,
Gyeonggi-do 410-820, Republic of Korea
d
Department of Food Science and Biotechnology, Dongguk University-Seoul, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 8 June 2016
Received in revised form 23 August 2016
Accepted 8 September 2016
Available online xxx
A new series of multi-heterocyclic Schiff base was constructed starting from 40-(imidazol-1-yl)-
acetophenone which was converted to its 2-bromoethanone precursor which on cyclic condensation
with thiourea yielded final thiazol-2-amine intermediate (3) to be reacted with substituted aldehydes to
generate final imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines (4a–4i). New Schiff base
was investigated for their in vitro cytotoxic efficacies against a panel of three human cancer cell lines
namely, MCF7 (human breast cancer), HCT116 (human colon cancer), and DU145 (human prostate
cancer) and one normal skin fibroblast (SF). Most of these synthetic derivatives shown important
cytotoxic actions against individual carcinoma cell line collections, but weak actions against SF, which is
as anticipated. Observations of SAR suggested that the difference in the characteristics of substituents
attached to the Schiff base function leads to the interesting variations within pharmacological effects of
resultant molecular systems. Structural analysis performed using FT-IR, 1H NMR, 13C NMR spectroscopy
and CHN analysis for final potent anticancer Schiff base, which warrant further investigations.
© 2016 Rahul V. Patel. Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of
Medical Sciences. Published by Elsevier B.V. All rights reserved.
Keywords:
Schiff Base
Imidazole
Thiazole
Anticancer
Drug designing
SAR
1. Introduction
interacted with azomethine’s nitrogen atom via forming a
hydrogen bond which interferes with normal cell processes [4]
and results in the destruction of enzymatic activity of cancerous
cells, thereby presents Schiff base as a potential target to discover
anticancer chemotherapeutics. Hence, in the current research, we
were directed to construct Schiff base derivatives involving the
presence of three different types of heterocycles as imidazole,
thiazole, and other heteroaromatics. Imidazole ring, highly polar
heterocycle, is an important five-membered aromatic heterocycle
widely present in natural products and synthetic molecules. It
readily binds with different targeted enzymes in a biological
Schiff bases, named after Hugo Schiff and their very first
formation was accomplished in the nineteenth millennium [1].
They are known as azomethine or imine as nitrogen analogue an
aldehyde or ketone structurally, where imine or azomethine group
found to replace the carbonyl group [2]. Schiff base is very widely
used and the most appreciated organic building blocks to have a
diverse range of pharmacological importance as well as a versatile
tool to explore in many other fields as biological, inorganic and
analytical chemistry. They hold
a spectrum of biological
importance as antioxidant, anthelmintic, antitubercular, anti-
inflammatory, anticancer, antimicrobial, anticonvulsant and so
forth [3]. The active centers of cell constituents are supposed to get
system via ion–dipole, coordination, van der Waals forces,
p–p
stacking, hydrophobic effects, cation– , and so on, because of its
p
unique electronrich characteristic which establishes diverse weak
interactions, thereby exhibiting broad bioactivities [5]. Hence, we
have selected imidazole as a starting heterocyclic core to build the
desire Schiff bases with intermediate thiazole entity which
represents a versatile tool to generate anticancer chemotherapeu-
tics [6]. Finally, different N, S and O-based heterocycles were
* Corresponding author.
E-mail address: rahul.svnit11@gmail.com (R.V. Patel).
Authors contributed equally.
1
http://dx.doi.org/10.1016/j.cclet.2016.10.021
1001-8417/© 2016 Rahul V. Patel. Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights
reserved.
Please cite this article in press as: N.M. Parekh, et al., Investigation of anticancer potencies of newly generated Schiff base
imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.10.021

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N.M. Parekh et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
Table 1
attached to the Schiff base function because, such heterocyclic
compounds have a considerable active role as antibacterial [7,8],
anti-viral [9], anti-fungal [10], anti-inflammatory [11], and anti-
tumor drugs [12–14].
Results of anticancer activity investigation for final Schiff base 4a–4i.
Entry
MTT assay (IC50 mmol/L ꢁ SD)a
MCF7b
HCT116c
DU145d
SFe
Heterocycles represent a common architectural device of most
promoted drugs and hence, we effort here to produce multi-
heterocyclic systems to be examined for their in vitro anticancer
results, because cancer provides being a major health issue in
developed along with developing countries. With >100 types of
cancer exist, 8.2 million people die each year from cancer, an
estimated 13% of all deaths worldwide and 70% the increase in new
cases of cancer expected over the next 2 decades [15]. In the
attempts to distinguish a variety of chemical substances that may
provide as leads for creating novel anticancer agents, nitrogen- and
sulfur- that contains heterocycles are of specific attention [16–18]
and the fact prompted us to generate anticancer multi-hetero-
aromatic systems as imidazolylphenylheterocyclic-2-ylmethyle-
nethiazole-2-amines. Recently, we have observed many structures
those represent similar features as ours with Schiff bases function
linked to 2-aminothiazole nucleus presenting interesting phar-
macological effects [19–22]. Hence, we attempt here to generate
Schiff base derivatives holding all three other building block as
diverse heterocycles which anticipated delivering significant
anticancer effects.
4a
4b
4c
4d
4e
4f
4g
4h
38.28 ꢁ 2.03
54.90 ꢁ 3.24
38.32 ꢁ 1.89
67.34 ꢁ 1.85
96.45 ꢁ 3.56
86.67 ꢁ 2.67
27.76 ꢁ 2.14
56.98 ꢁ 0.87
61.26 ꢁ 2.19
11.12 ꢁ 0.56
72.10 ꢁ 0.92
58.99 ꢁ 2.04
46.56 ꢁ 2.37
42.76 ꢁ 3.21
82.96 ꢁ 1.22
93.21 ꢁ 2.07
82.45 ꢁ 2.31
44.45 ꢁ 1.09
36.34 ꢁ 2.57
5.02 ꢁ 0.34
40.32 ꢁ 2.80
49.87 ꢁ 1.82
64.23 ꢁ 1.78
70.12 ꢁ 2.08
50.09 ꢁ 0.41
27.54 ꢁ 2.76
25.78 ꢁ 1.65
57.23 ꢁ 3.01
26.90 ꢁ 0.84
4.68 ꢁ 0.50
>50
>50
>50
>50
>50
>50
>50
>50
>50
>50
4i
Doxorubicin
a
Each value is the mean of three independent experiments.
Human breast cancer.
Human colon cancer.
Human prostate cancer.
Normal skin fibroblast cell.
b
c
d
e
formation of both intermediates. In further steps, intermediate 3
was reacted with various desired heterocyclic aldehyde entities (a–
i) in the presence of organocatalyst piperidine with molecular
sieve (4A) to furnish final thiazolyl Schiff bases 4a–4i [24]. All FT-IR
and 1H NMR data were in accurate accordance with the proposed
structural features of the final compounds and 1H NMR for
compound 4a as a representative analogue; N CH peak was
¼
2. Results and discussion
observed at 8.91 ppm which apparently confirms the accurate
synthesis. Mass spectral data were presented as M+1 molecular ion
peaks and which were also in accordance with the molecular
weights for the 4a–4i and elemental analysis data were in a
considerable range acceptable to confirm the correct formation of
anticipated structures.
2.1. Chemistry
Scheme 1 represents the chemical steps followed to obtain
desired Schiff base 4a–4i. 40-(Imidazol-1-yl)acetophenone was
selected as a starting material to be treated with aqueous HBr with
glacial acetic acid as well as bromine to give the first intermediate
derivative 1-(4-(1H-imidazol-1-yl)phenyl)-2-bromoethanone (2).
Intermediate 2 was subsequently reacted with thiourea in the
presence base to generate final thiazole-2-amine intermediate 3.
FT-IR spectra of intermediate 2 revealed aromatic stretching at
2976 cmꢀ1, carbonyl group characteristic peak at 1697 cmꢀ1 as well
as C-Br peak at 691 cmꢀ1 which ensure its correct formation. In
addition, FT-TR solid state spectrum obtained for intermediate 3
revealed NH2 characteristic peak at 3438 cmꢀ1 and thiazole ring
2.2. Pharmacology
The newly yielded multi-heterocomponent Schiff base 4a–4i
were subjected to the screening of their in vitro anticancer
potencies against a panel of three cancerous cell lines as MCF7
(human breast cancer), HCT116 (human colon cancer), and DU145
(human prostate cancer) as well as one non-cancer normal skin
fibroblast (SF) to inspect the cytotoxic character of the said
molecules toward the healthy cell line. The results of anticancer
peaks were observed as 1523 for C
¼N as well as 691 as CꢀꢀSꢀꢀC
linkage. 1H NMR spectra for intermediate 2 revealed peak for
COCH2Br linkage as a singlet 4.80 ppm, whereas, a peak at 7.71 ppm
was assigned to thiazole-H and such data confirmed the correct
screening are presented in Table 1 in terms of IC50s in
mmol/L, and
the bioassay data suggested that these new Schiff base displayed a
variable degree of anticancer activity with a broad scope of SAR
Het
NH2
O
O
N
S
N
CH2Br
thiourea
S
CH3
N
Br2
R-CHO
N
N
N
acetic acid
N
N
N
N
4'-(Imidazol-1-yl)acetophenone
N
1
2
3
4a-4i
Multi-heterocyclic Schiff base
O
S
NH
NH
S
Het
=
O
O
O
O
O
N
N
Furfural
e
2-Thiazolecarboxaldehyde
Pyrrole-2-carboxaldehyde
2-Thiophenecarboxaldehyde
2-Imidazolecarboxaldehyde
a
b
c
d
O
O
O
S
N
N
O
N
O
2-Benzofurancarboxaldehyde
2-Quinolinecarboxaldehyde
Benzothiazole-2-carboxaldehyde 2-Pyridinecarboxaldehyde
f
g
h
i
Scheme 1. Schematic presentation for the synthesis of imidazolylphenyl-heterocyclic-2-ylmethylene-thiazole-2-amines (4a–4i).
Please cite this article in press as: N.M. Parekh, et al., Investigation of anticancer potencies of newly generated Schiff base
imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.10.021

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N.M. Parekh et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
3
studies leading to a tool which can facilitate further rationale in
drug designing. It was noticed that primary imidazole and
intermediate thiazole rings were having an essential role to
provide promising cancerous cell inhibitory effects, whereas,
varying the type of coupled heterocyclic entity to the Schiff base
function has a key role in determining the final anticancer potency
of resultant molecule.
1.78
m
mol/L) and pyrrole (4d: 70.12 ꢁ 2.08
m
mol/L) with
57.23 ꢁ 3.01 of IC50 against DU-145 cell line. Overall, many of
the final Schiff base derivatives showed <50
m
mol/L of IC50
s
s
against all three cancerous cell lines and >50
against non-cancer cells which present them as leading candidates
for anticancer drug discovery.
mmol/L of IC50
A molecule with a benzothiazole entity (4g) connected to the
azomethine function showed the highest anticancer activity
3. Conclusion
against MCF-7 cell line with IC50 of 27.76 ꢁ 2.14
can be comparable to that of control drug doxorubicin with
mol/L of IC50 Moreover, the presence of two
heteroatoms as S and N was found beneficial to gain activity
against MCF-7 as compounds 4a with thiazole ring and 4c with
m
mol/L which
To conclude, a successful attempt has been made to furnish a
new series holding multi-hetero component resides with tremen-
dous anticancer action against three different cancerous cell lines.
Imidazole and thiazole core were kept constant in all final
molecules to get a regular anticancer data with a variable degree
of efficacy observed while varying heterocyclic moieties connected
to the Schiff base link. The correct formation of the desired
molecules was ensured utilizing different analytical techniques
followed by the inspection of their in vitro anticancer effects, in
11.12 ꢁ 0.56
m
.
imidazole moiety presented 38.28 ꢁ 2.03
mol/L of IC50s, respectively. All these three derivatives indicated
low cytotoxic character toward normal skin fibroblast cell with
>50 mol/L of IC50. It will be suffice to mention here that S
m
mol/L and 38.32 ꢁ1.89
m
m
heteroatom has a good role to play for the anticancer potency
against MCF-7 because a compound with S-heterocyclic entity in
terms of thiophene (4b) demonstrated good anticancer action with
which, all compounds presented <100 mmol/L of IC50s. Core
imidazole liked to the thiazole ring was very beneficial, as final
results also displayed anticipated potencies with thiazole core
lined to the Schiff base function. The presence of particular
heteroatom, as well as presence of an additional benzene ring, had
a significant effect against MCF-7 and DU-145, and heterocycles
with S atoms were more active, whereas, against HCT116, N-
heterocycles played a major role. Overall, 4a, 4g, and 4i showed
tremendous activity against all cancerous cell lines. In addition, all
54.90 ꢁ 3.24
bearing oxygenated heterocycles showed poor anticancer poten-
cies with IC50s >85 mol/L. Finally, molecules holding single N
atom as 4d, 4h and 4i appeared to have moderate anticancer effects
with IC50s, 67.34 ꢁ1.85 mol/L, 56.98 ꢁ 0.87 mol/L and
61.26 ꢁ 2.19 mol/L, respectively. Furthermore, quinolone ring
(4i) had the most influence on HCT116 cell line with 36.34 ꢁ 2.57
mol/L of the IC50 level and >50 mol/L of IC50 against non-cancer
mmol/L of IC50, whereas, compounds (4e and 4f)
m
m
m
m
compounds presented >50 mmol/L of IC50s against non-cancer
m
m
normal skin fibroblast (SF) cells which indicated tolerable
cytotoxic nature of these Schiff bases toward healthy cells. As
some substituent were found inactive, for example, those with O
heteroatom, more studies are obviously warranted to replace basic
core from imidazole and thiazole to other heteroatom-containing
rings to examine their overall influence on anticancer effects.
skin fibroblast cell being the most active analogue of the series
against the mentioned cancerous cell line. Similar to the activity
results observed against MCF-7, nitrogen-based heterocycles were
found remarkably active against HCT116 cell line as compounds 4c,
4d, and 4h with imidazole, pyrrole and pyridine rings demon-
strated 46.56 ꢁ 2.37
m
mol/L, 42.76 ꢁ 3.21
m
mol/L and 44.45 ꢁ1.09
m
mol/L, respectively, however their cytotoxicity towards SF was
4. Experimental
observed beyond 50
mmol/L, thus suggesting these N-heterocyclic
candidates as potentially active anticancer agent against human
colon cancer. The above data suggested that heterocycle with
single N atom were active against human colon cancer than those
carrying two N atoms. In fact, the presence of an additional
heteroatom in the form of S lead to the reduced activity of the
Reichert Thermover instrument was utilized to record melting
points of the final compounds which were uncorrected. FT-IR
spectra were recorded using KBr on Perkin Elmer RXI spectrometer.
Proton and carbon NMR data were recorded on Bruker AVANCE III
400 instrument spectrometer (1H NMR, 400 MHz; 13C NMR,
100 MHz) in the presence of TMS internal standard and with
DMSO. Mass spectra have been registered on JEOL-Accu TOF JMS-
T100LC DART-MS spectrometer. Microanalytical data were collect-
ed using Carlo Erba analyzer model 1108. TLC plates were used to
monitor the reaction as well as to identify the purity of the
prepared products.
molecule as 4g and 4a showed >70 mmol/L of IC50s against
HCT116 cell line, respectively. However, molecules bearing only a
single sulfur atom as compound 4b observed to have moderate
anticancer activity against HCT116 cell line with IC50 of
58.99 ꢁ 2.04
to activity recorded against MCF-7, compounds 4e and 4f were
found least sensitive against HCT116 cell line with >80 mol/L of
mmol/L. Lastly, with O-based heterocycles, similar
m
IC50s. Presence of an additional aromatic ring along with a
heterocyclic core in terms of benzofuran (4f), benzothiazole (4g)
and quinolone (4i) was a key to have successive anticancer action
against DU-145 prostate cancer cell line with IC50s, 27.54 ꢁ 2.76
4.1. Synthetic procedure for 1-(4-(1H-imidazol-1-yl)phenyl)-2-
bromoethanone (2)
In
a
flask charged with 40-(imidazol-1-yl)acetophenone
m
mol/L, 25.78 ꢁ 1.65
m
mol/L and 26.90 ꢁ 0.84
m
mol/L, respective-
(0.01 mol) with glacial acetic acid (20 mL) and aqueous hydro-
bromic acid (HBr) [48% (w/w)]. The resulting mixture was
immersed in an ice–salt mixture (0–5 ꢂC), and bromine
(0.01 mol) was added, and temperature of the reaction mixture
does not exceed 5 ꢂC. After completion of addition, it was stirred at
room temperature for 2–3 h. The progress of the reaction was
monitored by using TLC. After the completion of the reaction, the
suspension was poured onto crushed ice. The colorless precipitate
was filtered, repeatedly washed with water and dried at room
ly and it was found that heterocyclic with two different
heteroatoms (4g) was most active. Similarly, further data recorded
against DU-145 cell line proved that S has an excellent role to play
as molecules with thiazole (4a) and thiophene (4b) entities
showed 40.32 ꢁ 2.80
m
mol/L and 49.87 ꢁ1.82
mmol/L of IC50s,
toward SF cells presenting
respectively; and >50 of IC50
s
themselves as lead anticancer candidates against prostate cancer.
However, with an exception to the activity data for MCF-7 and
HCT116, a compound with O heteroatom in the form of furan (4e)
was as active as that with thiophene ring towards DU-145 cell line
temperature. Yield: 55%–57%, m.p: 147–149 ꢂC; FT-IR (KBr) cmꢀ1
:
2976 (Ar-stretching), 1697 (C
¼
O), 691 (CꢀꢀBr); 1H NMR (400 MHz,
with 50.09 ꢁ 0.41
m
mol/L of IC50. Finally, a derivative with a
DMSO–d6):
d
8.38 (s,1H), 8.13 (d,1H, J = 7.6 Hz,), 8.02 ꢀ7.96 (m, 2H),
pyridine (4h) ring has good action than imidazole (4c: IC50, 64.23 ꢁ
7.94 ꢀ7.87 (m, 2H), 7.84 (d, 1H, J = 7.5 Hz,), 4.80 (s, 2H). 13C NMR
Please cite this article in press as: N.M. Parekh, et al., Investigation of anticancer potencies of newly generated Schiff base
imidazolylphenylheterocyclic-2-ylmethylenethiazole-2-amines, Chin. Chem. Lett. (2016), http://dx.doi.org/10.1016/j.cclet.2016.10.021

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N.M. Parekh et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
(100 MHz, DMSO–d6):
129.9, 125.4, 123.7, 122.5, 34.23.
d
181.34, 150.12, 148.34, 137.6, 134.2, 132.7,
of fresh serum free media and 10
mL of MTT reagent (5 mg/mL) was
placed in the place of old media followed by the incubation at 37 ꢂC
for 4 h and lastly, this media was changed to 200 mL of DMSO
4.2. Synthetic procedure for 4-(4-(1H-imidazol-1-yl)phenyl)thiazol-
2-amine (3)
followed by last incubation at 37 ꢂC for 10 min. The absorbance at
570 nm was calculated on a spectrophotometer (Spectra Max,
Molecular devices) IC50 principles were identified from plot: % cell
viability (from control) versus concentration [23].
In a flask charged with compound 2 (0.01 mol), thiourea
(0.01 mol) and triethylamine (0.01 mol) and the reaction mixture
was refluxed for 10–12 h in 30 mL acetonitrile until the complete
consumption of starting material as detected by TLC. The reaction
mixture was then cooled, poured onto ice. The precipitate was
filtered, dried and recrystallised from ethanol. Yield: 45%–53%, m.
Conflicts of interest
The authors report no conflicts of interest.
Acknowledgments
p: 160–163 ꢂC; FT-IR (KBr) cmꢀ1: 3438 (NH2), 1577 (aromatic C
stretch),1523 (C
N) thiazole, 1154 (CꢀꢀN), 691 (CꢀꢀSꢀꢀC) thiazole;
1H NMR (400 MHz, DMSO–d6):
5.08 (s, 1H, NH2), 8.13 (d, 1H,
J = 7.5 Hz,), 7.98–7.91 (m, 2H), 7.84 (d, 1H, J = 7.5 Hz,), 7.71 (s, 1H),
7.61 (s, 2H), 7.48–7.42 (m, 2H). 13C NMR (100 MHz, DMSO–d6):
¼C
¼
This work is supported by Dongguk University-Seoul, Republic
of Korea, research funds 2016-2017. This article was supported by
the KU Research Professor Program of Konkuk University, Seoul,
Republic of Korea.
d
d
167.52, 153.71, 147.89, 146.21, 138.7, 134.6, 131.8, 128.7, 125.6, 124.6,
122.8, 121.9. Anal Calcd. for C22H22N2O3: C, 72.91; H, 6.12; N, 7.73;
Found: C, 72.76; H, 6.29; N, 7.62.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2016.10.021.
4.3. General method for the preparation of imidazolylphenyl-
heterocyclic-2-ylmethylene-thiazole-2-amines (4a–4i)
References
A mixture of substituted compound 3 (0.01 mol), substituted
heterocyclic aldehyde (0.01 mol) and piperidine (0.01 mol) was
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filtered, dried, and recrystallized using ethanol to give the final
compounds 4a–4i, for example, 4-(4-(1H-imidazol-1-yl)phenyl)-
N-(thiazol-2-ylmethylene)thiazol-2-amine (4a): Yield 65%. m.p.
213–214 ꢂC; FT-IR (KBr) cmꢀ1: 3067 (aromatic CꢀꢀH stretch), 1608
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¼
N) thiazole, 1147 (CꢀꢀN), 685 (CꢀꢀSꢀꢀC) thiazole; 1H NMR
(400 MHz, DMSO–d6):
d
8.91 (s,1H, N CH); 8.38 (s,1H), 8.13 (d,1H,
¼
J = 7.5 Hz), 8.05 (d, 1H, J = 7.5 Hz), 7.99–7.92 (m, 2H), 7.84 (d, 1H,
J = 7.5 Hz), 7.75 (s, 1H), 7.55 (d, 1H, J = 7.5 Hz), 7.49–7.43 (m, 2H). 13
NMR (100 MHz, DMSO–d6): 164.71, 164.03, 152.22, 147.72, 146.81,
C
d
144.11, 135.26, 131.25, 130.19, 125.67, 123.88, 122.45, 121.37, 118.30,
113.17, 112.61. EI-MS m/z (M+): 338.74; Anal Calcd. for C16H11N5S2:
C, 56.95; H, 3.29; N, 20.76; Found: C, 56.88; H, 3.35; N, 20.64.
4.4. In vitro evaluation of anticancer activity
Human cancer cell lines namely, MCF7 (human breast cancer),
HCT116 (human colon cancer), and DU145 (human prostate
cancer) and one normal skin fibroblast (SF), MTT [3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], DMEM,
trypsin–EDTA, RPMI and 96-well flat bottom tissue culture plates
were obtained from the commercial suppliers. Cancerous were
grown in DMEM medium, and SF cells were grown in RPMI
medium supplemented with 10% fetal bovine serum, 200 lg/mL
streptomycin, 100 l g/mL penicillin, 2 mmol/L L-glutamine, and
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compounds to be tested was prepared in DMSO with sterile PBS to
get required concentration. A standard MTT colorimetric assay was
performed for investigating the anticancer potential of 4a–4i
because MTT is a photosensitive compound and is consumed by
living organisms and a mitochondrial dehydrogenase enzyme
performs its reduction to a purple formazan product that is
impermeable to the cell membrane. DMSO solubilization of test
compounds yields liberation and resulting formazan product with
purple color is directly related to the cell viability. Cells placed in
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