Design and synthesis of three series of novel antitumor–azo derivatives

Article abstract of DOI:10.1007/s00044-017-1839-4

Three new series of thiazoles, quinolones, and thiazolidinones merged with benzimidazole, benzoxazole, and benzothiazole nuclei were synthesized. The compounds were subjected to Infrared, ¹H nuclear magnetic resonance, ¹³C nuclear ma

Full text of DOI:10.1007/s00044-017-1839-4

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-017-1839-4
ORIGINAL RESEARCH
Design and synthesis of three series of novel antitumor–azo
derivatives
1 ●
1
Phoebe F. Lamie John N. Philoppes
Received: 24 February 2016 / Accepted: 1 March 2017
Springer Science+Business Media New York 2017
©
Abstract Three new series of thiazoles, quinolones, and
thiazolidinones merged with benzimidazole, benzoxazole,
and benzothiazole nuclei were synthesized. The compounds
antimicrobial (Temiz et al. 1998; AsIm et al. 2004; Fran-
chini et al. 2009; Gajdos et al. 2009; Alang et al. 2010; Patel
and Shaikh 2010; Sathe et al. 2011), analgesic (Kohli et al.
2007), anti-inflammatory (Hibi et al. 1994; Pardasani et al.
1998; Gulcan et al. 2003; Venkatesh and Pandeya 2009;
Gupta and Rawat 2010; Kaur et al. 2010; Doma et al. 2014),
anticonvulsant (Siddiqui et al. 2007; Rana et al. 2008;
Siddiqui et al. 2009), and antidiabetic (Micael et al. 2005;
Nitta et al. 2008; Surya et al. 2009) activities. These phar-
macophores were designed and synthesized as kinase inhi-
bitors especially on Raf (Ramurthy et al. 2011), Aurora
1
were subjected to Infrared, H nuclear magnetic resonance,
1
3
C nuclear magnetic resonance, mass spectrometry, and
elemental analyses. Cytotoxic activity of compounds were
evaluated against breast (MCF-7) and colon (HCT-116) cell
lines. Seven of the compounds had IC50 values between
0
.0112 and 0.0198 µM and are hence more potent than the
reference drug doxorubicin (IC50 = 0.0084 and 0.0088 µM
against MCF-7 and HCT-116, respectively).
(
Aurrecoechea et al. 2010), and epidermal growth factor
●
●
Keywords Benzimidazole Benzoxazole Benzothiazole
derivatives Antitumor
receptor (Gullick 1991) which are over expressed in varying
levels in certain carcinoma such as breast, colon, and
bladder cancers (Ramurthy et al. 2011).
●
Some 2-aryl-benzothiazole derivatives (Fig. 1) have
received much attention due to their anticancer activities.
They include a series of 3-substituted-2-[4-aminophenyl]-
benzothiazoles (1) whose members were found to have anti-
tumor activity against breast cancer cell line MCF-7 and
MDA-468 (Shi et al. 1996; Hoi et al. 2006; Bhuva and Kini
2010). The bis-benzoxazole derivative (2) was also found to
be very active against different types of human cancer cell
lines (Jin et al. 2006). The dihydrobenzimidazole derivative
(3) was reported to have promising anticancer activity espe-
cially on HCT116 and HL 60 (Ramurthy et al. 2011). Another
benzothiazole derivative (4) was recently evaluated for
in vitro activity against lung and breast cancers. It competes
with ATP for binding at the catalytic domain of epidermal
growth factor receptor tyrosine kinase (Gabr et al. 2014).
A literature survey on compounds with benzothiazole
moieties linked to thiazole ring (5), thiazolidinone (6 and 7) or
quinolone derivative (8) revealed documented antitumor
activities against different cell lines such as MCF-7, MDA-
231, HeLa, overian, kidney, and EVSA-7 (Lipunova et al.
Introduction
Heterocyclic compounds have been popular in medicinal
chemistry research probably due to their wide and varied
biological activities. Examples include benzothiazole deri-
vatives and their isosteres benzoxazole and benzimidazole
derivatives with documented antitumor (Mortimer et al.
2
006; Caleta et al. 2009; Weng et al. 2009; Wee et al. 2009;
Bhuva and Kini 2010; Kamal et al. 2010; Racane et al.
010; Tzanopoulou et al. 2010; Kricker et al. 2012),
2
*
Phoebe F. Lamie
feby.farag@yahoo.com
feebi.lamey@pharm.bsu.edu.eg
1
Department of Pharmaceutical Organic Chemistry, Faculty of
Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt

Med Chem Res
Fig. 1 Structures of some of previously reported antitumor agents (1–8) containing benzimidazole, benzoxazole, and benzthiazole
pharmacophores
2
000; Mosula et al. 2009; Amnekar and Bhusari 2010; Hav-
rylyuk et al. 2010; Seetaramswamy et al. 2013; Pareek et al.
014; Prabhu et al. 2015). The documented anticancer activ-
Khattab et al. 2013). Cyanoacetylation of 2-(4-aminophe-
nyl)benzoxazole and benzothiazole derivatives 9b, c was
prepared using the same reported method for benzimidazole
analog 9a (Abd Ell-All et al. 2015). Spectroscopic data and
elemental analyses were done and confirmed the structures
of 10b, c. Infrared (IR) spectra of 10b, c showed the
appearance of two absorption bands at 2292, 2199, and
2
ities of such compounds guided our design of novel molecules
containing benzothiazole, oxazole or imidazole moieties
joined to thiazole, quinolones or thiazolidinone moieties in a
single molecular framework as shown by the structures in
Fig. 2 and screen them for their antitumor activity against solid
tumors, especially breast and colon cancers.
−1
1656, 1640 cm attributed to C≡N and C=O, respectively.
1
H NMR spectra of 10b, c revealed all the expected protons
of benzoxazole or benzothiazole moiety alongside with a
singlet signal at δ 3.98 and 3.99 for CH protons of 10b, c
2
Results and discussion
Chemistry
and a NH signal at δ 10.64 and 10.66. Two signals due to
1
3
CH and C≡N groups were found in C NMR spectra of
2
10b, c at δ 24.90, 24.93 and δ 125.19, 125.27, respectively.
2-Thioxothiazole derivatives 11a–f were achieved from
The starting materials 9a–c were prepared according to
the reaction of 10a–c with ethyl or phenylisothiocyanate
previously published method (Abdelgawad et al. 2013;
and elemental sulfur in presence of triethylamine as a base.

Med Chem Res
Fig. 2 General formula of the
newly synthesized
benzimidazole, benzoxazole,
and benzothiazole derivatives
(
11a–f, 17a, 17b, and 19a–f)
1
with their numbers in H NMR
and C NMR spectra
13
1
The structures of 11a–f were confirmed by H NMR
data, which revealed the absence of methylene singlet signal
of the parent compounds 10a–c and the emergence of ethyl
group protons in 11a, c, e at δ 1.21 and 4.27 with J value of
11.62 and 11.80 due to NH proton. The carbon atom in
C–CN was also appeared at δ 93.50 and 94.03, C=O
appeared at δ 162.12 and 164.06 and the carbon atom in
1
3
C–NH was appeared at δ 176.00 and 176.80 in C NMR
2
7
.2 Hz for 11a and 1.21 and 4.26 with J value of 7.8 in 11c
of quinolone derivatives in both 17a, b. Mass spectra of
17a, b revealed the molecular ion peak at m/z 302 (30.8%)
and 318 (7.8%), respectively (Scheme 2).
and 6.8 Hz in 11e, or phenyl ring protons in 11b, d, f.
Another exchangeable singlet signal for NH protons also
2
appeared at δ 7.09–7.82 confirmed the formation of 11a–f.
Moreover, C NMR showed signals newly formed of
thioxothiazole ring at δ 82.26–83.15 due to (C–S), δ
The mechanism of this reaction may be attributed to the
presence of CN group in o-position of cyanoacetyl deriva-
tives 16, which aided the intramolecular cyclization to take
place and the formation of the unexpected products 17a, b.
The plausible mechanism for this reaction was shown in
(Fig. 4).
The same reported method for the synthesis of 18a–c
was applied here (Abdelgawad et al. 2013; Kandeel et al.
2013). Treatment of chloroacetyl derivatives 18a–c with
ethyl or phenylisothiocyanate in presence of catalytic
amount of piperidine in ethanol at reflux temperature
afforded the corresponding thiazolidinone derivatives 19a–f
(Scheme 3).
1
3
1
56.72–154.19 (C–NH ) and 184.15–186.90 (C=S), which
2
proved the structures of 11a–f (Scheme 1).
The reaction seemed to be initiated via nucleophilic attack
of the carbanion 12 on sulfur followed by nucleophilic attack
of the thiol group (SH) lone pair in compound 13 on ethyl or
phenylisothiocyanate to yield the carbamodithioate deriva-
tives 14. The latter underwent interamolecular cyclization
followed by toutomerism to afford 11a–f as illustrated by the
following suggested mechanism, (Fig. 3).
Compounds 15a, b were prepared according to our
previously published work (Kandeel et al. 2013).
Upon applying the previous reaction conditions on 15a, b
for the preparation of cyanoacetyl derivatives 16, quinolone
The chemical structure of compounds 19a–f was
1
13
established by IR, H NMR, C NMR, mass spectral data
and elemental analyses. In IR spectra of 19a–f, the dis-
appearance of NH peak of the parent compounds 18a–c
derivatives 17a, b were formed instead.
1
1
H NMR spectra for 17a, b showed singlet D O
confirmed the structures. H NMR spectra of 19a–f
2
exchangeable peak at δ 6.90 and 7.43 for NH protons and
showed the disappearance of D O exchangeable singlet
2
2

Med Chem Res
Scheme 1 Reagents and
conditions: (i)
CNCH COOC H , ethanol,
2 2 5
reflux 3–5 h; (ii) RNCS, S, TEA,
ethanol, reflux, 4–6 h
signal of the parent compounds 18a–c and the appearance
of ethyl group protons as triplet and quartet peaks at δ
(HCT-116). Doxorubicin which is one of the most effective
anticancer agents was used as the reference drug in this
study.
1
.20–1.21 and 3.79–4.24 for CH and CH protons of
3 2
ethyl group, respectively in 19a, c, e or appearance of
The IC50 value, which corresponds to the concentration
required for 50% inhibition of cell viability, was calculated.
The IC50 in μM of the tested compounds compared to the
reference drug are shown in (Table 1) and represented
graphically in (Fig. 6).
1
3
additional phenyl protons in compounds 19b, d, f.
C
NMR spectra of compounds 19a–f exhibited three dis-
tinguished peak for thiazolidinone ring at δ 33.26–37.79
(
(
CH ), 156.17–165.25 (C=N) and 165.34–186.12 due to
C=O). Mass spectrum of 19e showed molecular ion peak
2
at m/z 353 and a base peak at m/z 265.
The reaction proceeded via nucleophilic attack of the lone
pair of acetamide NH to the carbon of the appropriate iso-
thiocyanate derivative to afford the iminothiol derivatives 20
followed by interamolecular nucleophilic attack of thiol lone
Biological results
From the results in Table 1, tested compounds were clas-
sified into three groups, group 1: for compounds 11a–f
which contain thiazole ring merged with benzimidazole,
oxazole and thiazole derivatives, it was found that cytotoxic
activity against MCF-7 for benzoxazole deivatives bearing
ethyl or phenyl moiety was more potent than thiazole or
imidazole isosters. Thus IC50 was 0.0125, 0.0198 μM for
11c, d while 0.0188, 0.0769 μM for 11e, f and 0.0273,
pair on (–CH Cl) with libration of HCl molecule to yield the
2
required compounds 19a–f, the suggested mechanism for the
formation of 19a–f was illustrated in (Fig. 5).
Biological evaluation
0.0862 μM for 11a, b, respectively. On the other hand,
Antitumor activity
all the compounds in this series were nearly equal in IC50
when screened against HCT-116 cell line (IC50 between
0.0358–0.0593 μM).
Concerning compounds 17a, b in group 2, benzoxazole
derivative showed higher activity than benzothiazole analog
All the newly synthesized target compounds were evaluated
for their in vitro cytotoxic activity against both human
adenocarcinoma cell line (MCF-7) and colon tumor cell line

Med Chem Res
Fig. 3 The proposed mechanism
for synthesis of 11a–f
for the two cell lines MCF-7 and HCT-116, with IC50 equal
MCF-7 cell line. The second observation came from the
precedence of benzothiazole cytotoxic activity against
MCF-7 in ethyl bearing compounds 19a–c.
0
.0267, 0.0357 μM and 0.0748, 0.0616 μM, sequentially.
By inspecting the last group of our test compounds
containing thiazolidinone ring system 19a–f against MCF-7
cell line, it was observed that: compounds 19a, 19c, and 19e
bearing ethyl substituent at imino nitrogen, the order of
reactivity was as follows: benzothiazol > benzimidazole >
benzoxazole and IC50 was equal to 0.0128, 0.0172, and
The three isosteres had nearly the same IC50 when tested
against HCT-116 cell line in 11a–f, while benzoxazole
returned to be the most potent between the test compounds
in 17a, b and 19a–f followed by benzothiazoles and
benzimidazoles.
0
.0302 μM, respectively. While the order of reactivity was
Generally, the best results were obtained by
11c, 19e, 19d, 19a, 11e, and 11d with IC50 between
(0.0125–0.0198 μM) for MCF-7, and 19c with IC50 equal to
0.0112 μM for HCT-116 and were attributed to presence of
either ethyl group and/or benzoxazole scaffold. The highest
cytotoxic activity was obtained when benzoxazole ring was
merged with ethyl substituent in compounds 11c (MCF-7)
and 19c (HCT-116).
In the future, the most active compounds in this study
will be screened against additional breast cancer cell lines
and hepatic carcinoma cell line (HepG2). Cell cycle analysis
and apoptosis effects will be evaluated. The mechanism of
action of the most active compounds will be demonstrated
using enzyme assay procedure.
changed to be benzoxazole 19d > benzothiazole 19f >
benzimidazole 19b for phenyl imino derivatives with IC50
of 0.0153, 0.0274 and 0.0937 μM, sequentially.
For screening compounds 19a–f against HCT-116, both
ethyl 19a, 19c, and 19e or phenyl derivatives 19b, 19d, and
1
9f exhibited the same order of reactivity. Thus, benzox-
azole showed the highest activity followed by benzothiazole
and benzimidazole derivatives which were near to each
other with IC50 equals 0.0112, 0.0309 μM for 19c, d,
0
1
.0801, 0.0533 μM for 19e, f and 0.0892, 0.0604 μM for
9a, b.
As a result, we concluded that, benzoxazole derivatives
showed the highest cytotoxic activity especially against

Med Chem Res
Scheme 2 Reagents and
conditions: (i) ICI, CH COOH,
CuCN; (ii) CNCH COOC
3
2
2 5
H ,
dimethylformamide, reflux 12 h
Fig. 4 The postulated
mechanism for formation of
1
7a, b
Conclusion
thiazole or thiazolidinone rings showed higher activity than
that of quinolones. Hence, benzoxazole derivative bearing
ethyl thiazole moiety 11c and benzothiazole derivative with
ethylthiazolidinone pharmacophore 19e exhibited the most
potent activity with IC50 = 0.0125 and 0.0128 µM,
sequentially when compared with the reference doxorubicin
(IC50 = 0.0084 µM). On the other hand, benzoxazole deri-
vative containing ethyl group on its thiazolidinone ring 19c
occupied the first stage in activity between test compounds
against HCT-116 cell line with IC50 = 0.0112 µM compar-
ing to doxorubicin IC50 (0.0088 µM).
In summary, three new series of azo-derivatives merged
with thiazole 11a–f, quinolone 17a, b and thiazolidinone
1
9a–f rings were synthesized. All the compounds were
evaluated in vitro against breast (MCF-7) and colon
HCT-116) cell lines. Most of test compounds exhibited
(
excellent antitumor activity, especially on MCF-7 cell line.
Regarding MCF-7, the arrangement of the most active
compounds
was:
11c > 19e > 19d > 19a > 11e > 11d
Compounds containing
(
IC50 = 0.0125–0.0198 µM).

Med Chem Res
Scheme 3 Reagents and
conditions: (i) ClCH COCl,
2
benzene, reflux, 30 min; (ii)
RNCS, piperidine, ethanol,
reflux, 8–10 h
Fig. 5 The suggested
mechanism for formation of
1
9a–c
Materials and methods
Experimental
III 400 MHz (Bruker BioSpin AG, Fällanden, Switzerland)
for H and 100 MHz for C with BBFO Smart Probe and
Bruker 400 AEON Nitrogen-Free Magnet, Faculty of
1
13
Pharmacy, Beni-Suef University, Egypt, in DMSO-d with
6
Chemistry
TMS as the internal standard, where J (coupling constant)
values are estimated in Hertz (Hz) and chemical shifts were
recorded in ppm on δ scale. Mass spectra (MS) were
recorded on a Hewlett Packard 5988 spectrometer (Palo
Alto, CA). Microanalyses for C, H, and N were carried out
on Perkin-Elmer 2400 analyzer (Perkin-Elmer, Norwalk,
CT) at the Micro analytical unit of Cairo University, Egypt,
Melting points were determined on a Thomas-Hoover
capillary apparatus and are uncorrected. IR spectra were
recorded as films on KBr plates using a Nicolet 550 Series
1
II Magna FT-IR spectrometer (Middleton, WI). H NMR
1
3
and C NMR spectra were measured on a Bruker Avance

Med Chem Res
Table 1 Results of in vitro cytotoxic activity of the synthesized
compounds 11a–f, 17a & b, 19a–f and doxorubicin on human breast
adenocarcinoma cell line (MCF-7) and colon cancer cell line (HCT-
1
16)
*
*
Compound no.
MCF-7 IC50 in µM
HCT-116 IC50 in µM
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1a
1b
1c
1d
1e
1f
0.0273
0.0862
0.0125
0.0198
0.0188
0.0769
0.0267
0.0748
0.0172
0.0937
0.0302
0.0153
0.0128
0.0274
0.0084
0.0526
0.0370
0.0593
0.0448
0.0582
0.0358
0.0357
0.0616
0.0892
0.0604
0.0112
0.0309
0.0801
0.0533
0.0088
Fig. 6 IC50 in μM of the synthesized compounds 11a–f, 17a & b,
1
9a–f and doxorubicin against human breast cancer cell line (MCF-7)
7a
7b
9a
9b
9c
9d
9e
9f
and human colon tumor cell line (HCT-116)
1
2
51.24 (C-7a), 162.20 (C-2), 170.02 (C=O); MS (m/z, %):
78 (M + 1, 13.60), 277 (M , 77.30), 68 (100.00); Anal.
+
Calcd for C H N O (277.28): C, 69.31; H, 4.00; N,
1
6 11 3 2
15.15. Found: C, 69.57; H, 3.85; N, 15.28.
N-(4-(benzo[d]thiazol-2-yl)phenyl)-2-cyanoacetamide
10c)
Doxorubicin
(
*
The values given are means of three experiments
Buff solid; yield 80%; m.p. 236–238 °C; IR (KBr) 3406
−
1 1
and all compounds were within±0.4% of the theoretical
values. All other reagents, purchased from the Aldrich
Chemical Company (Milwaukee, WI), were used without
further purification. The results and methods for preparation
of the target compounds were depicted in Schemes 1–3.
(2NH), 2292 (C≡N), 1640 (C=O) cm ; H NMR (DMSO-
d , δ ppm) δ 3.98 (s, 2H, CH ), 7.45 (t, 1H, J = 7.6 Hz,
6
2
Ar–H, H-6), 7.54 (t, J = 7.6 Hz, 1H, Ar–H, H-5), 7.76 (d,
2H, J = 8.8 Hz, Ar–H, H-3′, H-5′), 8.03 (d, 1H, J = 8 Hz,
Ar–H, H-7), 8.09 (d, 2H, J = 8.8 Hz, Ar–H, H-2′, H-6′),
8
.13 (d, 1H, J = 8 Hz, Ar–H, H-4), 10.64 (s, 1H, NH,
1
3
General method for preparation of compounds (10a–c)
exchangeable with D O); C NMR (DMSO-d , δ ppm):
2 6
2
4.93 (CH ), 119.64 (C-3′, C-5′), 121.11 (C-4), 121.36
2
A mixture of either compound 9a–c (0.001 mol) and excess
ethyl cyanoacetate was boiled under reflux in absolute ethanol
(C-7), 123.15 (C-6), 124.48 (C-5), 125.27 (C≡N), 126.03
(C-1′), 127.40 (C-2′, C-6′), 138.33 (C-4′), 141.21 (C-3a),
154.50 (C-7a), 161.40 (C-2), 169.70 (C=O); MS (m/z,%):
293 (M+, 25.01), 165 (100). Anal. Calcd for C H N OS:
(20 mL) for 3–5 h. After cooling, the solid separated was
filtered, dried, and recrystallized from ethanol to give 10a–c.
1
6 11 3
C, 65.51; H, 3.78; N, 14.32. Found: C, 65.37; H, 3.95;
N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide
N, 14.29.
(
10a)
General method for preparation of compounds (11a–f)
A mixture of compound 10a–c (0.01 mol), elemental sulfur
Paige solid; 85% yield; m.p. 265–267 °C as reported by
Abd Ell-All et al. (2015).
(0.32 g, 0.01 mol) and ethyl or phenylisothiocyanate
N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-cyanoacetamide (10b)
Buff solid; yield 85%; m.p. 267–269 °C; IR (KBr) 3439
derivative (0.01 mol) in ethanol (50 mL) containing trie-
thylamine (1 mL) was refluxed for 4–6 h (monitored by thin
layer chromatography (TLC). The solid separated on hot
was filtered, dried and recrystallized from ethanol 95% to
give 11a–f.
−
1 1
(
2NH), 2199 (C≡N), 1656 (C=O) cm ; H NMR (DMSO-
d , δ ppm) δ 3.99 (s, 2H, CH ), 7.37–7.43 (m, 2H, Ar–H, H-
6
2
4
8
, H-7), 7.75–7.80 (m, 4H, Ar–H, H-5, H-6, H-2′, H-6′),
.18 (d, 2H, J = 8.8 Hz, Ar–H, H-3′, H-5′), 10.66 (s, 1H,
N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-4-amino-3-ethyl-
2-thioxo-2,3-dihydrothiazole-5-carboxamide (11a)
1
3
NH, exchangeable with D O); C NMR (DMSO-d , δ
2
6
ppm): 24.90 (CH ), 110.06 (C-7), 119.11 (C-4), 119.71 (C-
2
3
′, C-5′), 123.05 (C-6), 124.8 (C-5), 125.19 (C≡N), 126.08
Grey solid; 75% yield; mp 280-282 °C; IR (KBr) 3415-
(
C-1′), 127.60 (C-2′, C-6′), 138.5 (C-4′), 141.50 (C-3a),
3176 (2NH and NH ), 1642 (C=O), 1235, 1181 (C=S)
2

Med Chem Res
cm− ; H NMR (DMSO-d , δ ppm): 1.21 (t, J = 7.2 Hz,
1
1
162.75 (C-2), 184.25 (C=S); MS (m/z, %): 397 (M + 1,
4.30), 396 (M+, 16.46), 210 (100%); Anal. Calcd for
C H N O S : C, 57.56; H, 4.07; N, 14.13. Found: C,
6
3
H, CH CH ), 4.27 (q, J = 7.2 Hz, 2H, CH CH ),
.18–7.19 (m, 2H, Ar–H, H-5, H-6), 7.56–7.58 (m, 2H,
2 3 2 3
7
1
9 16 4 2 2
Ar–H, H-4, H-7), 7.76 (s, 2H, NH , exchangeable with
57.33; H, 4.17; N, 13.99.
2
D O), 7.81 (d, J = 8.4 Hz, 2H, Ar-H, H-3′, H-5′), 8.11 (d, J
2
=
8.4 Hz, 2H, Ar–H, H-2′, H-6′), 9.44 (s, 1H, CONH,
4-Amino-N-(4-(benzo[d]oxazol-2-yl)phenyl)-3-phenyl-2-
thioxo-2,3-dihydrothiazole-5-carboxamide (11d)
exchangeable with D O), 12.79 (s, 1H, NH, exchangeable
with D O); C NMR (DMSO-d , δ ppm): 12.18 (CH ),
2
1
3
2
6
3
4
1.06 (CH ), 82.47 (C–S), 115.21 (C-4, C-7), 121.03 (C-3′,
Brown solid; 75% yield; m.p. 298–300 °C; IR (KBr)
2
C-5′), 122.53 (C-5, C-6), 125.09 (C-1′), 127.30 (C-2′, C-6′),
37.60 (C-4′), 140.98 (C-3a, C-7a), 151.61 (C-2), 152.76
3345–3234 (NH and NH ), 1634 (C=O), 1240, 1173
2
−1 1
1
(C=S) cm ; H NMR (DMSO-d , δ ppm): 7.10 (s, 2H,
6
(
C–NH ), 161.17 (C=O), 184.15 (C=S); MS (m/z, %): 395
NH , exchangeable with D O), 7.40–7.43 (m, 4H, Ar–H, H-
2
2
2
(
5
1
M+, 5.38), 98 (100). Anal. Calcd for C H N OS : C,
7.70; H, 4.33; N, 17.71. Found: C, 57.68; H, 4.15; N,
7.69.
7, H-2′′, H-4′′, H-6′′), 7.63–7.66 (m, 3H, Ar–H, H-4, H-3′′,
H-5′′), 7.76–7.79 (m, 2H, Ar–H, H-5, H-6), 7.92 (d, J = 8.8
Hz, 2H, Ar–H, H-2′, H-6′), 8.16 (d, J = 8.8 Hz, 2H, Ar–H,
1
9
17
5
2
1
3
H-3′, H-5′), 9.68 (s, 1H, NH, exchangeable with D O);
C
2
N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-4-amino-3-
NMR (DMSO-d , δ ppm): 82.39 (C-S), 111.24 (C-7),
6
phenyl-2-thioxo-2,3-dihydrothiazole-5-carboxamide (11b)
120.00 (C-4), 120.95 (C-3′, C-5′), 121.16 (C-1′), 125.28 (C-
6), 125.66 (C-5), 128.42 (C-2′, C-6′), 129.39 (C-4′′), 130.66
Grey solid; 54% yield; m.p. 165-167 °C; IR (KBr)
(C-2′′, C-6′′), 130.67 (C-3′′, C-5′′), 135.27 (C-1′′), 142.12
(C-4′), 142.95 (C-3a), 150.59 (C-7a), 153.43 (C–NH2),
161.19 (C=O), 162.76 (C-2), 184.24 (C=S); MS (m/z, %):
445 (M + 1, 5.79), 444 (M+, 17.30), 210 (100). Anal.
Calcd for C H N O S : C, 62.14; H, 3.63; N, 12.60.
3
410–3282 (NH and NH ), 1638 (C=O), 1236, 1180 (C=S)
2
−1
1
cm ; H NMR (DMSO-d , δ ppm): 7.02–7.04 (m, 2H,
6
Ar–H, H-2′′, H-6′′), 7.18–7.19 (m, 3H, NH , exchangeable
2
with D O and Ar–H, H-4′′), 7.41 (d, J = 6.4 Hz, 2H, Ar–H,
2
23 16 4 2 2
H-5, H-6), 7.60–7.66 (m, 4H, Ar–H, H-4, H-7, H-3′′, H-5′′),
Found: C, 61.97; H, 3.42; N, 12.53.
7
.83 (d, J = 8.4 Hz, 2H, Ar–H, H-3′, H-5′), 8.11 (d, J = 8.4
Hz, 2H, Ar–H, H-2′, H-6′), 9.53 (s, 1H, CONH, exchange-
4-Amino-N-(4-(benzo[d]thiazol-2-yl)phenyl)-3-ethyl-2-
thioxo-2,3-dihydrothiazole-5-carboxamide (11e)
able with D O), 12.78 (s, 1H, NH, exchangeable with D O);
2
2
1
3
C NMR (DMSO-d , δ ppm): 83.15 (C–S), 112.59 (C-4, C-
6
7), 121.78 (C-3′, C-5′), 122.00 (C-5, C-6), 123.42 (C-2′, C-
6′), 126.68 (C-1′), 129.37 (C-4′′), 130.20 (C-2′′, C-6′′),
130.73 (C-3′′, C-5′′), 135.00 (C-1′′), 136.68 (C-4′), 143.70
Buff solid; 80% yield; m.p. 244–246 °C; 3458–3251 (NH
−
1 1
and NH ), 1635 (C=O), 1239, 1199 (C=S) cm ; H NMR
2
(DMSO-d , δ ppm): 1.21 (t, J = 6.8 Hz, 3H, CH CH ), 4.26
6
2
3
(
C3a, C-7a), 1562.93 (C-2), 154.19 (C-NH ), 161.20
(q, J = 6.8 Hz, 2H, CH CH ), 7.43 (t, J = 7.6 Hz, 1H,
2
2
3
(
C=O), 186.90 (C=S); MS (m/z, %): 443 (M+, 3.32), 105
Ar–H, H-5), 7.53 (t, J = 7.6 Hz, 1H, Ar–H, H-6), 7.80 (s,
2H, NH , exchangeable with D O), 7.86 (d, J = 8.00 Hz,
(
100). Anal. Calcd for C H N OS : C, 62.28; H, 3.86; N,
2
3
17
5
2
2
2
1
5.79. Found: C, 62.17; H, 4.03; N, 15.67.
2H, Ar–H, H-3′, H-5′), 8.01-8.05 (m, 2H, Ar–H, H-4, H-7),
8
.11(d, J = 8.00 Hz, 2H, Ar–H, H-2′, H-6′), 9.54 (s, 1H,
1
3
4
-Amino-N-(4-(benzo[d]oxazol-2-yl)phenyl)-3-ethyl-2-
CONH, exchangeable with D O); C NMR (DMSO-d , δ
2 6
thioxo-2,3-dihydrothiazole-5-carboxamide (11c)
ppm): 12.19 (CH ), 41.05 (CH ), 82.39 (C–S), 121.03 (C-
3 2
3
′, C-5′), 122.69 (C-4), 123.00 (C-7), 125.71 (C-6), 127.05
Buff solid; 79% yield; m.p. 286–288 °C; IR (KBr) 3347-
(C-5), 127.89 (C-2′, C-6′), 128.16 (C-1′), 134.73 (C-7a),
3
259 (NH and NH ), 1636 (C=O), 1237, 1181 (C=S)
142.45 (C-4′), 152.92 (C-3a), 154.10 (C–NH ), 161.17
2
2
−1 1
cm ; H NMR (DMSO-d , δ ppm): 1.21 (t, J = 6.8 Hz,
(C=O), 167.50 (C-2), 184.24 (C=S); MS (m/z, %): 413 (M
+ 1, 0.34), 412 (M+, 0.91), 64 (100). Anal. Calcd for
C H N OS : C, 55.32; H, 3.91; N, 13.58. Found: C,
6
3
H, CH CH ), 4.26 (q, J = 6.8 Hz, 2H, CH CH ),
2 3 2 3
7
.39–7.41 (m, 2H, Ar–H, H-4, H-7), 7.75–7.79 (m, 2H,
1
9
16
4
3
Ar–H, H-5, H-6), 7.82 (s, 2H, NH , exchangeable with
55.24; H, 4.01; N, 13.55.
2
D O), 7.90 (d, J = 8.4 Hz, 2H, Ar–H, H-2′, H-6′), 8.14 (d, J
2
=
8.4 Hz, 2H, Ar–H, H-3′, H-5′), 9.58 (s, 1H, CONH,
4-Amino-N-(4-(benzo[d]thiazol-2-yl)phenyl)-3-phenyl-2-
thioxo-2,3-dihydrothiazole-5-carboxamide (11f)
1
3
exchangeable with D O); C NMR (DMSO-d , δ ppm):
2
6
1
1
6
2.20 (CH ), 41.05 (CH ), 82.26 (C-S), 111.22 (C-7),
3 2
19.98 (C-4), 120.90 (C-3′, C-5′), 121.09 (C-1′), 125.27 (C-
), 125.65 (C-5), 128.39 (C-2′, C-6′), 142.10 (C-4′), 142.94
Brown solid; 77% yield; mp 260–262 °C; 3459–3221 (NH
−
1 1
and NH ), 1636 (C=O), 1240, 1178 (C=S) cm ; H NMR
2
(
C-3a), 150.58 (C-7a), 153.00 (C-NH ), 161.20 (C=O),
(DMSO-d , δ ppm): 7.09 (s, 2H, NH , exchangeable with
2
6
2

Med Chem Res
1
3
D O), 7.40–7.46 (m, 3H, Ar–H, H-2′′, H-4′′, H-6′′), 7.53 (t,
2
D O); C NMR (DMSO-d , δ ppm): 93.50 (C–CN),
2 6
J = 8 Hz, 1H, Ar–H, H-6), 7.60–7.64 (m, 3H, Ar–H, H-5,
H-3′′, H-5′′), 7.88 (d, J = 8.4 Hz, 2H, Ar–H, H-3′, H-5′),
110.74 (C-7′), 113.00 (CN), 113.14 (C-4′), 114.03 (C-4a),
117.65 (C-8), 119.16 (C-6′), 120.01 (C-5′), 121.60 (C-6),
129.42 (C-7), 129.77 (C-5), 136.96 (C-8a), 142.5 (C-7′a),
150.29 (C-3′a), 152.96 (C-2′), 164.06 (C=O), 176.00
8
.02–8.07 (m, 3H, Ar–H, H-7, H-2′, H-6′), 8.13 (d, J = 8.4
Hz, 1H, Ar–H, H-4), 9.65 (s, 1H, CONH, exchangeable
1
3
with D O); C NMR (DMSO-d , δ ppm): 82.93 (C–S),
(C–NH ); MS (m/z, %): 318 (M+, 7.8), 105 (100). Anal.
2
6
2
1
6
21.06 (C-3′, C-5′), 122.74 (C-4), 123.02 (C-7), 125.74 (C-
), 127.08 (C-5), 127.94 (C-1′), 128.21 (C-2′, C-6′), 129.38
Calcd for C H N OS: C, 64.14; H, 3.17; N, 17.60. Found:
C, 64.28; H, 3.15; N, 17.69.
1
7 10 4
(
(
(
(
C-4′′), 130.66 (C-2′′, C-6′′), 130.76 (C-3′′, C-5′′), 134.74
C-1′′), 135.28 (C-7a), 142.48 (C-4′), 153.35 (C-3a), 154.10
General method for preparation of compounds (19a–f)
C-NH ), 161.15 (C=O), 167.50 (C-2), 186.19 (C=S); MS
2
m/z, %): 461 (M + 1, 0.41), 460 (M+, 0.88), 64 (100).
A mixture of compound 18a–c (0.01 mol) and ethyl or
phenylisothiocyanate derivative (0.01 mol) in ethanol
(50 mL) containing piperidine (1 mL) was refluxed for
Anal. Calcd for C H N OS : C, 59.98; H, 3.50; N, 12.16.
Found: C, 60.13; H, 3.45; N, 12.19.
2
3
16
4
3
8
–10 h (monitored by TLC), then left to cool. The solid
General method for preparation of compounds (17a, b)
separated upon pouring onto ice/water was filtered, dried
and recrystallized from acetone to give 19a–f.
To a solution of compound 15b or 15c (0.01 mol) in dime-
thylformamide (20 mL), ethyl cyanoacetate (0.05 mol,
3-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-2-(ethylimino)
thiazolidin-4-one (19a)
5
.65 g) was added. The reaction mixture was heated under
reflux for 12 h. After cooling, the reaction mixture was
poured onto ice-cooled water. The separated solid was fil-
tered, dried, and crystallized from ethanol 95% to give 17a, b.
Paige solid; 58% yield; mp 238-240 °C; IR (KBr) 3426
−
1 1
(NH), 1719 (C=O) cm ; H NMR (DMSO-d , δ ppm):
6
1
.21 (t, J = 6.4 Hz, 3H, CH CH ), 4.11 (s, 2H, CH ), 4.27
2 3 2
4
-Amino-6-(benzo[d]oxazol-2-yl)-2-oxo-1,2-
(q, J = 6.4 Hz, 2H, CH CH ), 7.40–7.42 (m, 2H, Ar–H, H-
2
3
dihydroquinoline-3-carbonitrile (17a)
5, H-6), 7.80 (d, J = 8.8 Hz, 2H, Ar–H, H-3′, H-5′), 7.90 (d,
J = 8.4 Hz, 2H, Ar–H, H-4, H-7), 8.14 (d, J = 8.8 Hz, 2H,
Ar–H, H-2′, H-6′), 9.57 (s, 1H, NH, exchangeable with
D O), C NMR (DMSO-d , δ ppm): 9.03 (CH CH ), 34.50
2 6 2 3
(CH ), 46.34 (CH CH ), 121.19 (C-4, C-7), 124.93 (C-1′),
2 2 3
Paige solid; 62% yield; m.p. 225–227 °C; IR (KBr)
1
3
3
444–3249 (NH and NH ), 2217 (C≡N), 1634 (C=O)
2
−1
1
cm ; H NMR (DMSO-d , δ ppm): 6.90 (s, 2H, NH ,
6
2
exchangeable with D O), 6.95 (d, J = 8.8 Hz, 1H, Ar–H, H-
127.36 (C-5, C-6), 129.22 (C-2′, C-6′), 130.74 (C-3′, C-5′),
135.15 (C-4′), 140.97 (C-3a, C-7a), 153.10 (C-2), 161.15
(C=N), 186.12 (C=O); MS (m/z, %): 336 (M+, 5.53), 70
(100). Anal. Calcd for C H N OS: C, 64.26; H, 4.79; N,
2
7
2
8
′), 7.35–7.38 (m, 2H, Ar–H, H-5′, H-6′), 7.70–7.72 (m,
H, Ar–H, H-7, H-8), 8.07 (d, J = 8.4 Hz, 1H, Ar–H, H-4′),
.15 (s, 1H, Ar–H, H-5), 11.80 (s, 1H, NH, exchangeable
1
8 16 4
1
3
with D O); C NMR (DMSO-d , δ ppm): 94.03 (C–CN),
16.65. Found: C, 64.41; H, 4.57; N, 16.73.
2
6
111.05 (C-7′), 114.11 (CN), 116.25 (C-4′), 117.53 (C-4a),
119.63 (C-8), 121.60 (C-6), 125.19 (C-5′), 125.31 (C-6′),
132.84 (C-7), 133.12 (C-5), 136.80 (C-8a), 141.5 (C-3′a),
150.38 (C-7′a), 154.36 (C-2′), 162.12 (C=O), 176.80
3-(4-(1H-Benzo[d]imidazol-2-yl)phenyl)-2-(phenylimino)
thiazolidin-4-one (19b)
(
C–NH ); MS (m/z,%): 302 (M+, 30.8), 165 (100). Anal.
Paige solid; 55% yield; m.p. 241–216 °C; IR (KBr) 3394
2
−
1 1
Calcd for C H N O : C, 67.55; H, 3.33; N, 18.53. Found:
(NH), 1669 (C=O) cm ; H NMR (DMSO-d , δ ppm):
1
7
10
4
2
6
C, 67.31; H, 3.17; N, 18.52.
4.42 (s, 2H, CH ), 7.40 (d, J = 8.8 Hz, 2H, Ar–H, H-2′′, H-
2
6
′′), 7.44–7.68 (m, 5H, Ar–H, H-5, H-6, H-3′, H-5′, H-4′′),
4
-Amino-6-(benzo[d]thiazol-2-yl)-2-oxo-1,2-
7.80 (d, J = 8.4Hz, 2H, Ar–H, H-4, H-7), 8.02–8.19 (m,
4H, Ar–H, H-2′, H-6′, H-3′′, H-5′′), 10.55 (s, 1H, NH,
dihydroquinoline-3-carbonitrile (17b)
1
3
exchangeable with D O); C NMR (DMSO-d , δ ppm):
2
6
Brown solid; 59% yield; m.p. 175–177 °C; IR (KBr)
34.35 (CH ), 111.25 (C-4, C-7), 113.26 (C-2′), 119.95 (C-2′
2
3
456–3248 (NH and NH ), 2212 (C≡N), 1640 (C=O)
′, C-6′′), 120.04 (C-5, C-6), 122.03 (C-4′), 125.30 (C-4′′),
125.76 (C-2′, C-6′), 128.84 (C-3′, C-5′), 130.02 (C-3′′, C-5′
′), 141.97 (C-1′′), 141.99 (C3a, C-7a), 150.59 (C-2), 162.50
(C=N), 165.34 (C=O); MS (m/z, %): 384 (M+, 1.06), 57
(100). Anal. Calcd for C H N OS: C, 68.73; H, 4.19; N,
2
−1 1
cm ; H NMR (DMSO-d , δ ppm): 7.40–7.43 (m, 3H,
NH , exchangeable with D O and Ar–H, H-7′), 7.76–7.81
6
2
2
(
m, 3H, Ar–H, H-4′, H-5′, H-6′), 7.96 (d, J = 8.4 Hz, 1H,
Ar–H, H-8), 8.36 (d, J = 8.4 Hz, 1H, Ar–H, H-7), 9.05 (s,
H, Ar–H, H-5), 11.62 (s, 1H, NH, exchangeable with
2
2 16 4
1
14.57. Found: C, 68.53; H, 3.98; N, 14.37.

Med Chem Res
3
-(4-(Benzo[d]oxazol-2-yl)phenyl)-2-(ethylimino)
3-(4-(Benzo[d]thiazol-2-yl)phenyl)-2-(phenylimino)
thiazolidin-4-one (19f)
thiazolidin-4-one (19c)
Grey solid; 57% yield; m.p. 195–197 °C; IR (KBr) 1722
Brown solid; 48% yield; m.p. 180–182 °C; IR (KBr) 1699
−
1 1
−1 1
(
C=O) cm ; H NMR (DMSO-d , δ ppm): 1.21 (t, J = 5.2
(C=O) cm ; H NMR (DMSO-d , δ ppm): 4.05 (s, 2H,
6
6
Hz, 3H, CH CH ), 3.79 (q, J = 5.2 Hz, 2H, CH CH ), 4.08
CH ), 7.18–7.20 (m, 1H, Ar–H, H-4′′), 7.41–7.69 (m, 4H,
2
3
2
3
2
(
7
s, 2H, CH ), 7.18 (d, J = 6.8 Hz, 2H, Ar–H, H-3′, H-5′),
.41–7.43 (m, 2H, Ar–H, H-4, H-7), 7.78–7.80 (m, 2H,
Ar–H, H-3′, H-5′, H-2′′, H-6′′), 7.79–7.96 (m, 5H, Ar–H, H-
6, H-2′, H-6′, H-3′′, H-5′′), 8.14-8.35 (m, 3H, Ar–H, H-4,
2
1
3
Ar–H, H-5, H-6), 8.20 (d, J = 6.8Hz, 2H, Ar–H, H-2′, H-
6
H-5, H-7); C NMR (DMSO-d , δ ppm): 37.79 (CH ),
6
2
1
3
′); C NMR (DMSO-d , δ ppm): 12.72 (CH CH ), 33.26
120.04 (C-4), 120.11 (C-7), 122.73 (C-2′′, C-6′′), 123.10
(C-6), 125.82 (C-5), 127.10 (C-4′′), 128.57 (C-2′, C-6′),
128.63 (C-3′, C-5′), 128.72 (C-1′), 129.03 (C-3′′, C-5′′),
134.79 (C-7a), 141.55 (C-4′), 141.70 (C-1′′), 154.06 (C-3a),
165.25 (C=N), 165.56 (C-2), 167.28 (C=O); MS (m/z, %):
401 (M+, 6.42), 67 (100). Anal. Calcd for C H N OS :
6
2
3
(
CH ), 44.17 (CH CH ), 111.30 (C-7), 120.11 (C-4),
2 2 3
1
5
1
22.47 (C-2′, C-6′), 122.69 (C-1′), 125.31 (C-6), 125.78 (C-
), 129.12 (C-3′, C-5′), 142.08 (C-4′), 150.66 (C-3a),
51.95 (C-7a), 156.44 (C=N), 162.66 (C-2), 172.17
(
C=O); MS (m/z, %): 337 (M+, 3.07), 77 (100). Anal.
2
2
15
3
2
Calcd for C H N O S: C, 64.08; H, 4.48; N, 12.45.
C, 65.81; H, 3.77; N, 10.47. Found: C, 65.73; H, 3.92; N,
1
8 15 3 2
Found: C, 64.03; H, 4.47; N, 12.49.
10.41.
3
-(4-(Benzo[d]oxazol-2-yl)phenyl)-2-(phenylimino)
Biological activity
thiazolidin-4-one (19d)
Materials and methods
Grey solid; 57% yield; mp 200-202 °C; IR (KBr) 1670
−
1 1
(
C=O) cm ; H NMR (DMSO-d , δ ppm): 4.21 (s, 2H,
In this study, doxorubicin (DOX) was chosen as a reference
anticancer drug, as it is one of the most effective anticancer
agents. Serial dilutions were made to reach final con-
centration of (5, 12.5, 25, and 50 μg/mL). All the test
compounds and the reference drug (DOX), were dissolved
in 20% DMSO in concentration 1 mg/mL. All chemicals
used in this study are of high analytical grade. They were
obtained from Sigma-Alderich. Human breast cancer
(MCF-7) and colon cancer (HCT-116) cell lines were sup-
plied from the American Type Cell Culture Collection
(Manassas, USA) and was maintained at Al-Azhar Uni-
versity, Cairo, Egypt.
6
CH ), 6.93–7.01 (m, 2H, Ar–H, H-2′′, H-6′′), 7.12–7.22 (m,
H, Ar–H, H-4′′), 7.35–7.46 (m, 4H, Ar–H, H-4, H-7, H-3′,
H-5′), 7.71–7.84 (m, 4H, Ar–H, H-5, H-6, H-2′, H-6′), 8.10-
.36 (m, 2H, Ar–H, H-3′′, H-5′′); C NMR (DMSO-d , δ
6
2
1
1
3
8
ppm): 33.49 (CH ), 111.53 (C-7), 120.46 (C-4) 121.17 (C-
2
2
1
1
(
(
′′, C-6′′), 124.80 (C-6), 125.50 (C-5), 126.25 (C-4′′),
26.82 (C-1′), 128.37 (C-2′, C-6′), 129.75 (C-3′, C-5′),
29.93 (C-3′′, C-5′′), 138.62 (C-4′), 141.95 (C-1′′), 148.47
C-3a), 150.82 (C-7a), 156.17 (C=N), 162.11 (C-2), 171.97
C=O); MS (m/z, %): 385 (M+, 4.39), 256 (100). Anal.
Calcd for C H N O S: C, 68.55; H, 3.92; N, 10.90.
2
2 15 3 2
Found: C, 68.63; H, 3.77; N, 11.19.
Measurement of potential cytotoxic activity by
sulforhodamine-B stain (SRB) assay
3
-(4-(Benzo[d]thiazol-2-yl)phenyl)-2-(ethylimino)
thiazolidin-4-one (19e)
The cytotoxic activity was performed using SRB assay
Brown solid; 52% yield; m.p. 200-202 °C; IR (KBr) 1719
according to the method of Skehan et al. (1990). Cells were
plated in 96-multiwell plate (10 cells/well) for 24 h before
−
1 1
4
(
C=O) cm ; H NMR (DMSO-d , δ ppm): 1.20 (t, J = 7.2
6
Hz, 3H, CH CH ), 3.63 (s, 2H, CH ), 4.24 (q, J = 7.2 Hz,
treatment with the compounds to allow attachment of cells
to the wall of the plates. Different concentrations of the test
compound (5, 12.5, 25, and 50 µg/mL) were added to the
cell monolayer. Triplicate wells were prepared for each
individual dose. Monolayer cells were incubated with the
different compounds for 48 h at 37 °C and in atmosphere of
2
3
2
2
H, CH CH ), 7.39 (d, J = 8.8 Hz, 2H, Ar–H, H-3′, H-5′),
2
3
7
.74–7.76 (m, 2H, Ar–H, H-5, H-6), 7.85–7.87 (m, 2H,
Ar–H, H-4, H-7), 8.13 (d, J = 8.8 Hz, 2H, Ar–H, H-2′, H-
1
3
6
′); C NMR (DMSO-d , δ ppm): 9.02 (CH CH ), 33.49
6 2 3
(
CH ), 44.07 (CH CH ), 119.79 (C-4), 120.07 (C-7),
2 2 3
1
1
1
21.16 (C-6), 122.75 (C-5), 126.22 (C-2′, C-6′), 128.58 (C-
′), 129.74 (C-3′, C-5′), 133.25 (C-4′), 134.79 (C-7a),
54.09 (C-3a), 156.19 (C=N), 167.30 (C-2), 171.98
5% CO . After 48 h, cells were fixed, washed and stained
2
with SRB stain. Excess stain was washed with acetic acid
and attached stain was recovered with Tris EDTA buffer.
Color intensity was measured in an ELISA reader. The
relation between surviving fraction and drug concentration
was plotted and IC50 (the concentration required for 50%
(
C=O); MS (m/z, %): 353 (M+, 24.42), 265 (100). Anal.
Calcd for C H N OS : C, 61.16; H, 4.28; N, 11.89.
Found: C, 60.99; H, 4.17; N, 12.01.
1
8
15
3
2

Med Chem Res
Gajdos P, magdolen P, Zahradnik P, Foltinova P (2009) New con-
jugated benzothiazole-N-oxides: Synthesis and biological activ-
ity. Molecules 14:5382–5388
inhibition of cell viability) was calculated for each
compound.
Gulcan HO, Unlu SE, Banoglu MF, Sahin (2003) Synthesis of New 4-
(
5-Chloro-2-oxo-3H-benzoxazol-3-yl)butanamide derivatives and
their analgesic and anti- inflammatory properties. Turk J Chem
7:467–476
Acknowledgements The authors would like to thank NMR Lab
members, Faculty of Pharmacy, Beni-Suef University, Beni-Suef,
Egypt for their helping in analysing all the required samples using
proton NMR and DEPT-Q techniques.
2
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