Synthesis, anti-proliferative activity, SAR, and kinase inhibition studies of thiazol-2-yl- substituted sulfonamide derivatives

Article abstract of DOI:10.1002/jccs.201800312

A series of novel thiazol-2-yl substituted-1-sulfonamide derivatives were synthesized from anilines. This involved the coupling of sulfonyl chlorides with thiazol amine to obtain the final compounds 7a–7j and 8a–8j. All synthesized compounds were screened for anticancer activity against MCF-7, HeLa, A-549, and Du-145 cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Preliminary bioassay suggests that most of the compounds show anti-proliferation to different degrees, with doxorubicin used as positive control. The synthesized compounds show IC₅₀ values in the range 2.74–8.17 μM in the different cell lines. The compounds 7d, 7e, 8a, 8d, and 8e were active compared to doxorubicin. The compounds having butyl and pantyl chains were more active than their lower and higher carbon chains and also their ring counterparts.

Full text of DOI:10.1002/jccs.201800312

Received: 6 August 2018
Revised: 9 October 2018
Accepted: 12 October 2018
DOI: 10.1002/jccs.201800312
C O M M U N I C A T I O N
Synthesis, anti-proliferative activity, SAR, and kinase inhibition
studies of thiazol-2-yl- substituted sulfonamide derivatives
Chandrakant D. Pawar1 | Sadhana L. Chavan1 | Umakant D. Pawar2 | Dattatraya N. Pansare1 |
Santosh V. Deshmukh3 | Devanand B. Shinde4
1Department of Chemical Technology, Dr.
A series of novel thiazol-2-yl substituted-1-sulfonamide derivatives were synthe-
Babasaheb Ambedkar Marathwada University,
Aurangabad, Maharashtra, India
2Regional Forensic Science Laboratories,
sized from anilines. This involved the coupling of sulfonyl chlorides with thiazol
amine to obtain the final compounds 7a–7j and 8a–8j. All synthesized compounds
were screened for anticancer activity against MCF-7, HeLa, A-549, and Du-145
cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
Aurangabad, Maharashtra, India
3Department of Chemistry, Vasantrao Naik
Collage, Aurangabad, Maharashtra, India
(MTT) assay. Preliminary bioassay suggests that most of the compounds show
anti-proliferation to different degrees, with doxorubicin used as positive control.
The synthesized compounds show IC50 values in the range 2.74–8.17 μM in the
different cell lines. The compounds 7d, 7e, 8a, 8d, and 8e were active compared to
doxorubicin. The compounds having butyl and pantyl chains were more active than
their lower and higher carbon chains and also their ring counterparts.
4Shivaji University, Kolhapur, Maharashtra, India
Correspondence
Chandrakant D. Pawar, Department of Chemical
Technology, Dr. Babasaheb Ambedkar
Marathwada University, Aurangabad, Maharashtra
431004, India.
Email: dbschandrakant13@gmail.com
KEYWORDS
anticancer, cyclization, kinase inhibitors, sulfonamide, thiazol-2-yl
inhibition,[7] in vitro anti-HIV activity,[8] COX-2 inhibition,
1
| INTRODUCTION
[9]
glycosidase inhibitory activity,[10] antimalarial activity,[11]
and carbonic anhydrase inhibition.[12] The benzo[d]thiazol-
2-yl nucleus is extensively used because of its endocyclic NH2
such that its combination with other groups forms various
building blocks and key intermediates showing promising bio-
logical activities.[13,14] By considering the diversified biologi-
cal activity of benzo[d]thiazol-2-yl, and in continuation of our
research work on such compounds,[15–19] we report here the
synthesis of two series of compounds with the sulfonamide
group. All the synthesized compounds were tested for their
biological activity against different cell lines and in enzymatic
studies.
In recent years, kinase studies have become an important and
most extensively investigated activity in the search for anti-
cancer agents. Kinases play an important role in the function-
ing of the cell; the normal or abnormal functioning of a cell
depends on different kinases. Different kinases act as potential
therapeutic targets in different cancers. The present che-
motheraptic treatment of patients increases the median sur-
vival by several months.[1,2] Thus, there is need to develop
new strategies for the treatment of cancer. Protein kinase rep-
resents an excellent therapeutic target from the biological and
drug development perspectives. The United States Food and
Drug Administration (USFDA) has approved kinase inhibitors
for the treatment of cancer. Keeping this is mind, there is con-
tinuous research going on.[3–5] In the present work, we have
chosen the 2-aminobenzo[d]thiazol-2-yl nucleus and its deriv-
atives for anticancer study. The benzo[d]thiazol-2-yl deriva-
tives show anti-mycobacterial [6] and monoacylglycerol lipase
2
| RESULTS AND DISCUSSION
We synthesized N-(benzo-[d]-thiazol-2-yl)-substituted-
1-sulfonamide (7a–7j) and N-(naptho-[2,3-d]-thiazol-2-yl)-
substituted-1-sulfonamide (8a–8j) using aniline (1a) and
© 2018 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2018;1–8.
http://www.jccs.wiley-vch.de
1

2
PAWAR ET AL.
naphthalene-2-amine (1b), as shown in Schemes 2 and 3. In
Scheme 1 we show the synthesis of substituted-[d]-thiazol-
2-amines 5a and 5b. The compounds benzo-(d)-thiazol-
2-amine (5a) and naphtha-[2,3-d]-thiazol-2-amine (5b) are
the key intermediates for the synthesis of the final com-
pounds 7a–7j and 8a–8j. For the synthesis of compound 5a,
researchers have used different strategies like the one-step
scheme using CuI, DABCO, NaH, etc.[20–26] Some
researchers have used ammonium/potassium thiocyanate,
cyclization reactions, oxidizing agents, etc.[27–31] We have
optimized the synthesis of 5a in stepwise manner to get good
yield, neat reaction profile, and under less harsh conditions.
The optimized steps are shown in Scheme 1.
For the optimization of the reaction condition, we have
taken 1a as a representative compound and carried out all
the screening reactions to obtain 5a. For the synthesis of
compound 5b, the same experimental protocol was used. We
screened different bases and solvents for obtaining good
yields. For optimization of step (a), we used toluene and
benzene as solvents and NaHCO3, Na2CO3, K2CO3 and
CS2CO3 as bases.
By using NaHCO3 as the base, after 2 hr we obtained
15 and 10% yield, after 5 hr 30 and 31% yield, and after
12 hr 60 and 45% of compound 3a in toluene and benzene,
respectively. The reaction of aniline with thiophosgene in
toluene at room temperature for 12 hr resulted in 60% yield
of compound 3a. For increasing the yield of 3a, we used
Na2CO3 as the base and toluene and benzene as solvents.
The reaction yields were monitored by liquid
chromatography-mass spectrometry (LC-MS) after 3, 5, and
12 hr. After 12 hr, the highest yield obtained was 30 and
20%, respectively, for toluene and benzene. Further, we used
the strong base K2CO3 in toluene and benzene for 3, 6, and
12 hr; again, the highest yield was obtained after 12 hr
(35 and 25%, respectively, for the corresponding solvents).
By using Cs2CO3 as base in both solvents for 12 hr at room
temperature, the obtained yield was 30 and 20%, i.e. there
was a decrease in the yield. For step (a), the reaction with
NaHCO3 as base and toluene as solvent at room temperature
for 12 hr resulted in a yield of 60% for compound 3a. The
same reaction conditions were used for the synthesis of
compound 3b.
In step (b), compound 3a was reacted with aq. ammonia
in tetrahydrofuran (THF) at room temperature for 12 hr, and
there was 30% formation of compound 4a. The reaction was
heated for 2 hr at 100ꢀC in a steel bomb vessel for 6 hr, and
there was formation of 15% of the product. There was a mul-
tiple spot streak on the thin-layer chromatography (TLC),
indicating that we had to decrease the temperature and time;
so in the next reaction we used 70ꢀC for 2 hr, and there was
30% formation of compound 4a, with the TLC profile look-
ing better than the earlier one. When we heated compound
3a at 100ꢀC for 2 hr, the TLC profile was prominent with
the formation of one distinct spot. After isolation, we
obtained 80% of the compound 4a. The same reaction condi-
tions were applied for the synthesis of compound 4b to
obtain 70% yield.
In step (c), compound 4a was heated with Br in acetic
acid for 2 hr, and there were multiple spot streaks on the
TLC. So we stirred the reaction mixture at room temperature
for 1 hr, with no change in the starting material. Further,
when we continued the reaction for 3 hr, there was slight for-
mation of a new spot (charring in ninhydrine stain) along
with unreacted starting material. We continued the reaction
for 12 hr at room temperature, whereupon the staring mate-
rial disappeared, and after work-up and isolation, there was
80% formation of compound 5a. For the synthesis of com-
pound 5b, the same reaction condition was used, giving 70%
yield. The detailed experimental procedures are given in
Section 3.
In Schemes 2 and 3, the compound 5a/5b was reacted
with different sulfonyl chlorides (6a–6j) in DCM and
pyridine at room temperature to obtain the final compounds
7a–7j/8a–8j with yields in the range of 70–80% (after opti-
mization). We used aliphatic sulfonyl chlorides for the sul-
fonamide coupling reactions and different bases like
triethylamine (TEA), diisopropylethylamine (DIPEA), pyri-
dine, and 4-dimethylaminopyridine (DMAP), but all failed
to give good yields, they being in the range 40–50% after
O
S
O
N
S
O
S
R
(a)
N
O
NH2
NH
R
Cl
S
7a-7j
5a
6a-6j
SCHEME 2 Synthesis of N-(benzo-(d)-thiazol-2-yl)-substituted-
1-sulfonamides (7a–7j). Reagents and conditions: (a): Substituted sulfonyl
chloride (6a–6j), pyridine, DCM, 0ꢀC to room temperature, 12 hr
H
S
NH2
Cl
N
N
S
N
NH
2 (c)
(b)
(a)
NH2
Cl
S
S
2
1a-1b
5a-5b
3a-3b
4a-4b
O
S
O
NH2
NH2
N
S
O
S
NH2
R
(a)
N
S
O
NH2
NH
R
Cl
1a
1b
1a-1b
6a-6j
5b
8a-8j
SCHEME 1 Synthesis of substituted-(d)-thiazol-2-amines (5a, 5b).
Reagents and conditions: (a): NaHCO3, thiophosgene (2), 0ꢀC to room
SCHEME 3 Synthesis of N-(naptho-(2,3-d)-thiazol-2-yl)-substituted-
1-sulfonamides (8a–8j). Reagents and conditions: (a): Substituted sulfonyl
chloride (6a–6j), pyridine, DCM, 0ꢀC to room temperature, 12 hr
temperature, 12 hr; (b): aq. ammonia, THF, 100ꢀC, 2 hr; (c): Br2\ACOH,
0ꢀC to room temperature, 12 hr

PAWAR ET AL.
3
isolation. We tried combinations of different bases and sol-
vents [DCM/TEA (1:1) (55% yield); DCM/pyridine (1:1)
(75% yield), DCM/DIPEA (1:1) (35% yield)], among which
the DCM/pyridine combination worked well with 70–80%
yield of sulfonamide coupling. In the other two combina-
tions, the yield was in the range 35–55%, so DCM/pyridine
(1:1) was used as base and solvent, respectively, for sulfon-
amide coupling to obtain the desired compounds 7a–7j/8a–
8j. The detailed experimental procedure, work-up, and yield
are given in Section 3.
layer was separated, washed with brine (30 mL), dried over
anhydrous Na2SO4, and concentrated in vacuo. The crude
product obtained was purified by column chromatography
(silica, 100–200 mesh, 5–20% EtOAc in hexane) to afford
1-isothiocyanatobenzene (3a, 4.35 g, 60%, b.p. 224–226ꢀC
[430ꢀF]) as a light yellow oil.
Synthesis
of
2-isothiocyanatonaphthalene
(3b)
[1636-33-5]: The experimental procedure was the same as
for 3a, and compound 3b was obtained with 60% yield from
compound 1b.
Table of substituents (6a–6j):
3.1.2
| Step b: Synthesis of 1-phenylthiourea (4a) [103-85-5]
Sr. no.
R
Sr. no.
R
To a stirred solution of 3a (2.00 g, 14.8 mmol) in THF
(20 mL) was added aq. ammonia (20 mL) in a steel bomb
vessel, and the reaction mixture was stirred at 100ꢀC for
2 hr. Progress of the reaction was monitored by TLC and the
consumption of starting material by LC-MS. After comple-
tion, the reaction mixture was poured into cold H2O
(30 mL) and extracted with DCM (2 × 20 mL). The organic
layer was separated, washed with brine (20 mL), dried over
anhydrous Na2SO4, and concentrated in vacuo to afford
1-phenylthiourea (4a, 1.80 g, 80%, m.p. 148–151ꢀC) as a
yellow solid.
The crude obtained was used further for the next reaction
without purification.
Synthesis of 1-(naphthalen-3-yl)thiourea (4b): The
experimental procedure was the same as for 4a to obtain
compound 4b with 70% yield from compound 3b.
6a=7a=8a
6b=7b=8b
6c=7c=8c
–CH3
–C2H5
–C3H7
6f=7f=8f
6g=7g=8g
6h=7h=8h
–C7H15
–C8H17
6d=7d=8d
6e=7e=8e
–C4H9
6i=7i=8i
6j=7j=8j
–C5H11
3
| EXPERIMENTAL
All chemicals, unless otherwise specified, were purchased
from commercial sources and were used without further
purification. The major chemicals were purchased from
Sigma–Aldrich and Avra labs. The development of the
reactions was monitored by TLC analysis on Merck pre-
coated silica gel 60 F254 aluminum sheets and visualized
by UV light. The melting points were recorded on an SRS
Optimelt melting point apparatus, and are reported uncor-
3.1.3
| Step c: Synthesis of benzo[d]thiazol-2-amine (5a)
[136-95-8]
1
To a 0ꢀC cooled 4a (1.52 g, 1.0 mmol) in a round-bottomed
flask was added Br2/AcOH (15 mL). The reaction mixture
was allowed to come to room temperature and stirred for
12 hr. Progress of the reaction was monitored by TLC and
the consumption of the starting material by LC-MS. After
completion, the reaction mixture was poured into cold H2O
(30 mL) and basified by using saturated aq. Na2CO3
(30 mL). The reaction mixture was extracted with DCM
(2 × 20 mL). The organic layer was separated, washed with
brine (20 mL), dried over anhydrous Na2SO4, and concen-
trated in vacuo to afford benzo[d]thiazol-2-amine (5a,
1.20 g)[31] as a yellow solid.
rected. The H NMR spectra were recorded on a 400 MHz
Varian NMR spectrometer. The 13C spectra were recorded
on a 100 MHz Varian NMR spectrometer. The chemical
shifts are reported as NMR spectra δ ppm units. The fol-
lowing abbreviations are used: singlet (s), doublet (d), trip-
let (t), quartet (q), multiplet (m), and broad (br s). The
mass spectra were recorded with a Micromass-QUATTRO-
II (WATERS) mass spectrometer.
3.1 | Experimental procedure for the synthesis of
thiazol-2-yl-substituted-1-sulfonamide derivatives (7a–7j
and 8a–8j)
The crude obtained was used further for the next reaction
without purification.
3.1.1
[103-72-0]
| Step a: Synthesis of 1-isothiocyanatobenzene (3a)
Yellow solid; yield 80%; m.p. 168–171ꢀC; 1H NMR
(400 MHz, DMSO-d6, ppm) δ 8.01 (d, J = 7.8 Hz, 1H),
7.63–7.52 (m, J = 14.2, 4.2 Hz, 2H), 7.19 (t, J = 7.8 Hz,
1H), 6.48 (br s, 2H).
To a stirred solution of comp-1a (5.00 g, 53.7 mmol) in tolu-
ene (50 mL). Cooled reaction mixture to 0 C and added
ꢀ
NaHCO3 (9.0 g, 107 mmol), stirred reaction mixture for 10
min. Added comp-2 (9.27 g, 80.6 mmol) and allowed reac-
tion mixture come to room temperature and stirred for 12 h.
Progress of the reaction was monitored by TLC and the con-
sumption of the starting material by LC-MS. After comple-
tion, the reaction mixture was poured into cold H2O
(50 mL) and extracted with DCM (2 × 30 mL). The organic
Naphtho[2,3-d]thiazol-2-amine (5b) [39608-20-3]: The
experimental procedure was the same as for 5a to obtain
compound 5b with 70% yield from compound 4b.
Yellow
semisolid;
yield
70%;
1H
NMR
(400 MHz,DMSO-d6, ppm) δ 8.56 (s, 1H), 7.96 (d,

4
PAWAR ET AL.
J = 8.2 Hz, 1H), 7.82–7.78 (q, J = 13.8, 5.8 Hz, 2H),
7.57–7.47 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t, J = 7.6 Hz,
1H), 6.38 (br s, 2H).
229 (M + H); HPLC 99.3% RT 9.84 min; Anal. Calc. for
C8H8N2O2S2: C, 42.09; H, 3.53; N, 12.27; S, 28.09;
Found: C, 42.07; H, 3.55; N, 12.29; S, 28.11.
3.1.4
and 8a–8j
| Step d: General procedure for the synthesis of 7a–7j
3.3.2
[549542-441]
| N-(Benzo[d] thiazol-2-yl)ethane-1-sulfonamide (7b)
Yellow solid; yield 82%; m.p. 116–117ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.58 (br s, 1H), 8.0 (d,
J = 7.8 Hz, 1H), 7.64–7.52 (m, J = 14.2, 4.2 Hz, 2H), 7.18
(t, J = 7.8 Hz, 1H), 3.26–3.19 (q, J = 14.4, 7.2 Hz, 2H),
1.16 (s, 3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 173.4,
148.2, 126.4, 125.6, 124.8, 121.6, 121.5, 44.2, 14.2; LC-MS
m/z (%): 243 (M + H); HPLC 98.24% RT 8.81 min; Anal.
Calc. for C9H10N2O2S2: C, 44.61; H, 4.16; N, 11.56; S,
26.47; Found: C, 44.63; H, 4.17; N, 11.54; S, 26.46.
To a stirred solution of 5a/5b (1 equiv.) in DCM (10 vol.)
was added pyridine (10 vol.) at 0ꢀC. The reaction mixture
was stirred at the same temperature for 15 min, compounds
6a–6j (1.2 equiv.) were dropwise/portionwise were added,
and the reaction mixture was stirred at room temperature for
12 hr. Progress of the reaction was monitored by TLC and
LC-MS. After completion, the reaction mixture was poured
on cold 2 N aqueous HCl (10 vol.) and stirred for 30 min.
After completion, work-up was done by two methods for
the different derivatives.
3.3.3
[1239727-42-4]
| N-(Benzo[d] thiazol-2-yl)propane-1-sulfonamide (7c)
In Method 1, precipitates formed in some derivatives,
which were filtered. The obtained solid was washed with
water (25 mL), cold diethyl ether (25 mL), and cold pentane
(25 mL) to afford crude 7a–7j/8a–8j. In Method 2, extraction
was done with DCM (2 × 20 mL), and the organic layer
was separated, washed with brine (10 mL), dried over anhy-
drous Na2SO4, and concentrated in vacuo to afford crude
7a–7j/8a–8j. The crude compound obtained was purified by
column chromatography (silica, 100–200 mesh, 5–40%
EtOAc in hexane) to afford compounds 7a–7j/8a–8j.
Brown solid; yield 86%; m.p. 151–152ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.58 (br s, 1H), 8.0 (d,
J = 7.8 Hz, 1H), 7.64–7.52 (m, J = 14.2, 4.2 Hz, 2H), 7.18
(t, J = 7.8 Hz, 1H), 3.26–3.21 (d, J = 12.6, 6.4 Hz, 2H),
1.64 (q, J = 14.8, 7.4 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H); 13
C
NMR (CDCl3, 100 MHz, ppm) = δ 174.2, 147.6, 125.8,
124.5, 122.4, 122.2, 121.4, 52.4, 12.8, 12.4; LCMS m/z (%):
257 (M + H); HPLC 96.6% RT 7.34 min; Anal. Calc. for
C10H12N2O2S2: C, 46.85; H, 4.72; N, 10.93; S, 25.02;
Found: C, 46.84; H, 4.73; N, 10.92; S, 25.03.
3.2 | Synthesis of N-(benzo[d]-thiazol-2-yl)-ethane-
1-sulfonamide (7b)
3.3.4
| N-(Benzo[d] thiazol-2-yl)butane-1-sulfonamide (7d)
To a stirred solution of 5a (0.15 g, 0.10 mmol) in DCM
(1.5 mL) was added pyridine (1.5 mL) at 0ꢀC. The reaction
mixture was stirred at the same temperature for 15 min.
Then, 6b (0.15 g, 0.12 mmol) was added dropwise and the
reaction mixture was stirred at room temperature for 12 hr.
The progress of the reaction was monitored by TLC and LC-
MS. After completion, the reaction mixture was poured on
cold 2 N aqueous HCl (5 mL) and stirred for 15 min. Extrac-
tion was done with DCM (2 × 5 mL), the organic layer was
separated, washed with brine (5 mL), dried over anhydrous
Na2SO4, and concentrated in vacuo. The crude product
obtained was purified by column chromatography (silica,
100–200 mesh, 30% EtOAc in hexane) to afford N-(benzo
[d]-thiazol-2-yl)-ethane-1-sulfonamide (7b; 0.2 g, 82%) as a
yellow solid.
[899014-38-1]
Brown solid; yield 89%; m.p. 153–154ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.58 (br s, 1H), 8.0 (d,
J = 7.8 Hz, 1H), 7.64–7.52 (m, J = 14.2, 4.2 Hz, 2H), 7.18
(t, J = 7.8 Hz, 1H), 3.26–3.21 (d, J = 12.6, 6.4 Hz, 2H),
1.64 (q, J = 14.8, 7.4 Hz, 4H), 0.96 (t, J = 7.4 Hz, 3H); 13
C
NMR (CDCl3, 100 MHz, ppm) = δ 173.8, 148.1, 125.8,
125.7, 124.9, 121.6, 121.4, 52.1, 19.1, 18.9, 12.6; LC-MS
m/z (%): 271 (M + H); HPLC 97.8% RT 7.12 min; Anal.
Calc. for C11H14N2O2S2: C, 48.87; H, 5.22; N, 10.36; S,
23.72; Found: C, 48.88; H, 5.21; N, 10.35; S, 23.73.
3.3.5
| N-(Benzo[d] thiazol-2-yl)pentane-1-sulfonamide (7e)
Brown solid; yield 85%; m.p. 149–150ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.58 (br s, 1H), 8.0 (d,
J = 7.8 Hz, 1H), 7.62–7.54 (q, J = 16.6, 8.8 Hz, 2H), 7.18
(t, J = 7.8 Hz, 1H), 3.20–3.12 (d, J = 14.4, 7.2 Hz, 2H),
1.36–1.14 (q, J = 14.8, 7.4 Hz, 6H), 0.78 (t, J = 7.4 Hz,
3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 173.7, 148.2,
125.8, 125.7, 124.9, 121.6, 121.4, 51.8, 34.1, 24.2, 14.8,
12.8; LC-MS m/z (%): 285 (M + H); HPLC 96.6% RT
7.32 min; Anal. Calc. for C12H16N2O2S2: C, 50.68; H,
5.67; N, 9.85; S, 22.55; Found: C, 50.67; H, 5.68; N,
9.86; S, 22.54.
3.3 | Spectral data
3.3.1
| N-(Benzo[d] thiazol-2-yl)methane-1-sulfonamide (7a)
[35607-92-2]
Brown oil; yield 84%; 1H NMR (400 MHz,DMSO-d6, ppm)
δ 8.58 (br s, 1H), 8.0 (d, J = 7.8 Hz, 1H), 7.64–7.52 (m,
J = 14.2, 4.2 Hz, 2H), 7.18 (t, J = 7.8 Hz, 1H), 2.97 (s,
3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 173.4, 148.2,
126.5, 125.6, 123.2, 121.6, 121.5, 41.3; LC-MS m/z (%):

PAWAR ET AL.
5
3.3.6
|
N-(Benzo[d] thiazol-2-yl)heptane-1-sulfonamide (7f)
3.3.11
| N-(Naphtho[2,3-d] thiazol-2-yl)methane-
Off-white solid; yield 89%; m.p. 134–135ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.58 (br s, 1H), 8.0 (d,
J = 7.8 Hz, 1H), 7.62–7.54 (q, J = 16.6, 8.8 Hz, 2H), 7.18
(t, J = 7.8 Hz, 1H), 3.22 (q, J = 13.2, 4.2 Hz, 2H), 2.61 (q,
J = 12.4, 6.8 Hz, 2H), 1.24 (q, J = 12.4, 6.8 Hz, 2H),
1.21–1.04 (q, J = 14.8, 7.4 Hz, 6H), 0.78 (t, J = 7.4 Hz,
3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 173.7, 148.2,
125.8, 125.7, 124.9, 121.6, 121.4, 52.4, 30.4, 29.2, 28.8,
24.1, 14.8, 12.8; LC-MS m/z (%): 313 (M + H); HPLC
98.2% RT 6.84 min; Anal. Calc. for C14H20N2O2S2: C,
53.82; H, 6.45; N, 8.97; S, 20.52; Found: C, 53.81; H,
6.44; N, 8.96; S, 20.50.
1-sulfonamide (8a)
Brown solid; yield- 85%; m.p. 176–177ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.88 (br s, 1H), 8.58 (s, 1H),
7.96 (d, J = 8.2 Hz, 1H), 7.83–7.79 (q, J = 13.8, 5.8 Hz,
2H), 7.56–7.46 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t,
J = 7.6 Hz, 1H), 2.97 (s, 3H); 13C NMR (CDCl3, 100 MHz,
ppm) = δ 174.1, 148.3, 126.2, 125.9, 124.8, 124.6, 124.5,
122.7, 122.6, 108.6, 41.2; LC-MS m/z (%): 278 (M + H);
HPLC 99.2% RT 9.14 min; Anal. Calc. for
C12H10N2O2S2: C, 51.78; H, 3.62; N, 10.06; S, 23.04;
Found C, 51.79; H, 3.64; N, 10.04; S, 23.05.
3.3.12
| N-(Naphtho[2,3-d] thiazol-2-yl)ethane-
1-sulfonamide (8b)
Yellow solid; yield 80%; m.p. 184–185ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.88 (br s, 1H), 8.58 (s, 1H),
7.96 (d, J = 8.2 Hz, 1H), 7.83–7.79 (q, J = 13.8, 5.8 Hz,
2H), 7.56–7.46 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t,
J = 7.6 Hz, 1H), 3.26–3.19 (q, J = 14.4, 7.2 Hz, 2H), 1.16
(s, 3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 174.1,
148.4, 126.4, 125.8, 124.9, 124.6, 124.5, 122.8, 122.6,
108.6, 43.8, 14.6; LC-MS m/z (%): 293 (M + H); HPLC
99.2% RT 8.25 min; Anal. Calc. for C13H12N2O2S2: C,
53.40; H, 4.14; N, 9.58; S, 21.93; Found C, 53.41; H,
4.13; N, 9.59; S, 21.92.
3.3.7
| N-(Benzo[d] thiazol-2-yl)octane-1-sulfonamide (7g)
Off-white Solid; yield 88%; m.p. 136–137ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.58 (br s, 1H), 8.0 (d,
J = 7.8 Hz, 1H), 7.62–7.54 (q, J = 16.6, 8.8 Hz, 2H), 7.18
(t, J = 7.8 Hz, 1H), 2.22 (q, J = 13.2, 4.2 Hz, 2H), 1.61 (q,
J = 12.4, 6.8 Hz, 2H), 1.38 (q, J = 12.4, 6.8 Hz, 2H),
1.18–1.04 (q, J = 14.8, 7.4 Hz, 8H), 0.81 (t, J = 7.4 Hz,
3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 173.7, 148.2,
125.8, 125.7, 124.9, 121.6, 121.4, 52.4, 30.2, 29.8, 29.1,
28.8, 24.2, 14.8, 12.8; LC-MS m/z (%): 327 (M + H); HPLC
96.5% RT 7.10 min; Anal. Calc. for C15H22N2O2S2: C,
55.18; H, 6.79; N, 8.58; S, 19.64; Found: C, 55.17; H,
6.78; N, 8.59; S, 19.65.
3.3.13
| N-(Naphtho[2,3-d] thiazol-2-yl)propane-
1-sulfonamide (8c)
Yellow solid; yield 86%; m.p. 186–187ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.88 (br s, 1H), 8.58 (s, 1H),
7.96 (d, J = 8.2 Hz, 1H), 7.83–7.79 (q, J = 13.8, 5.8 Hz,
2H), 7.56–7.46 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t,
J = 7.6 Hz, 1H), 3.26–3.21 (d, J = 12.6, 6.4 Hz, 2H), 1.64
(q, J = 14.8, 7.4 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, ppm) = δ 173.1, 148.4, 128.4,
127.6, 125.2, 125.1, 124.8, 121.8, 108.2, 53.1, 12.1, 11.4;
LC-MS m/z (%): 307 (M + H); HPLC 96.4% RT 9.28 min;
Anal. Calc. for C14H14N2O2S2: C, 54.88; H, 4.61; N,
9.14; S, 20.93; Found C, 54.89; H, 4.60; N, 9.13; S, 20.94.
3.3.8
1-sulfonamide (7h)
| N-(Benzo[d] thiazol-2-yl)cyclopropane-
1
Brown semisolid; yield 82%; H NMR (400 MHz,DMSO-
d6, ppm) δ 8.58 (br s, 1H), 8.01 (d, J = 7.8 Hz, 1H),
7.62–7.52 (m, J = 14.2, 4.2 Hz, 2H), 7.19 (t, J = 7.8 Hz,
1H), 2.48 (m, 1H), 0.72–0.84 (q, J = 14.8, 7.4 Hz, 4H); LC-
MS m/z (%): 255 (M + H).
3.3.9
1-sulfonamide (7i)
| N-(Benzo[d] thiazol-2-yl)cyclobutane-
1
3.3.14
1-sulfonamide (8d)
| N-(Naphtho[2,3-d] thiazol-2-yl)butane-
Yellow semisolid; yield 86%; H NMR (400 MHz,DMSO-
d6, ppm) δ 8.59 (br s, 1H), 8.01 (d, J = 7.8 Hz, 1H),
7.63–7.52 (m, J = 14.2, 4.2 Hz, 2H), 7.19 (t, J = 7.8 Hz,
1H), 2.52 (m, 1H), 1.12 (m, 4H), 0.98 (m, 2H); LC-MS m/z
(%): 269 (M + H).
Yellow solid; yield 87%; m.p. 189–190ꢀC; 1H NMR
(400 MHz, DMSO-d6, ppm) δ 8.88 (br s, 1H), 8.58 (s, 1H),
7.96 (d, J = 8.2 Hz, 1H), 7.83–7.79 (q, J = 13.8, 5.8 Hz,
2H), 7.56–7.46 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t,
J = 7.6 Hz, 1H), 3.26–3.21 (d, J = 12.6, 6.4 Hz, 2H), 1.64
(q, J = 14.8, 7.4 Hz, 4H), 0.96 (t, J = 7.4 Hz, 3H); 13C
NMR (CDCl3, 100 MHz, ppm) = δ 173.1, 148.4, 128.4,
127.6, 125.2, 125.1, 124.8, 121.8, 108.2, 51.9, 22.8, 22.2,
12.8; LC-MS m/z (%): 321 (M + H); HPLC 95.8% RT
9.08 min; Anal. Calc. for C15H16N2O2S2: C, 56.22; H,
5.03; N, 8.74; S, 20.01; Found C, 56.20; H, 5.01; N,
8.73; S, 20.02.
3.3.10
1-sulfonamide (7j)
| N-(Benzo[d] thiazol-2-yl)cyclopentane-
Brown solid; yield 81%; 1H NMR (400 MHz,DMSO-d6,
ppm) δ 8.57 (br s, 1H), 8.0 (d, J = 7.8 Hz, 1H), 7.61–7.52
(m, J = 14.2, 4.2 Hz, 2H), 7.17 (t, J = 7.8 Hz, 1H), 2.54 (m,
1H), 1.88–1.79 (m, 2H), 1.78–1.57 (m, 4H), 1.11–1.06 (m,
2H); LC-MS m/z (%): 283 (M + H).

6
PAWAR ET AL.
3.3.15
|
N-(Naphtho[2,3-d] thiazol-2-yl)pentane-
3.3.19
| N-(Naphtho[2,3-d] thiazol-2-yl)cyclobutane-
1-sulfonamide (8e)
1-sulfonamide (8i)
Off-white solid; yield 88%; m.p. 179–180ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.88 (br s, 1H), 8.58 (s, 1H),
7.96 (d, J = 8.2 Hz, 1H), 7.83–7.79 (q, J = 13.8, 5.8 Hz,
2H), 7.56–7.46 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t,
J = 7.6 Hz, 1H), 3.20–3.12 (d, J = 14.4, 7.2 Hz, 2H),
1.36–1.14 (q, J = 14.8, 7.4 Hz, 6H), 0.78 (t, J = 7.4 Hz,
3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 173.1, 148.4,
128.4, 127.6, 125.2, 125.1, 124.8, 121.8, 108.2, 52.1, 28.4,
21.6, 18.8, 12.6; LC-MS m/z (%): 335 (M + H); HPLC
98.6% RT 9.14 min; Anal. Calc. for C16H18N2O2S2: C,
57.46; H, 5.42; N, 8.38; S, 19.17; Found C, 57.45; H,
5.41; N, 8.39; S, 19.16.
Gray semisolid; yield 79%; H NMR (400 MHz,DMSO-d6,
ppm) δ 8.88 (br s, 1H), 8.59 (s, 1H), 7.97 (d, J = 8.2 Hz,
1H), 7.83–7.78 (q, J = 13.8, 5.8 Hz, 2H), 7.58–7.45 (m,
J = 14.4, 7.2 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 2.50 (m,
1H), 1.10 (m, 4H), 0.99 (m, 2H); LC-MS m/z (%):
319 (M + H).
1
3.3.20
| N-(Naphtho[2,3-d] thiazol-2-yl)cyclopentane-
1-sulfonamide (8j)
Yellow solid; yield 84%; 1H NMR (400 MHz,DMSO-d6,
ppm) δ 8.88 (br s, 1H), 8.60 (s, 1H), 7.95 (d, J = 8.2 Hz,
1H), 7.84–7.78 (q, J = 12.8, 5.4 Hz, 2H), 7.58–7.46 (m,
J = 12.4, 6.2 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 2.52 (m,
1H), 1.87–1.80 (m, 2H), 1.78–1.57 (m, 4H), 1.11–1.06 (m,
2H); LC-MS m/z (%): 333 (M + H).
3.3.16
| N-(Naphtho[2,3-d] thiazol-2-yl)heptane-
1-sulfonamide (8f)
Off-white solid; yield 85%; m.p. 164–163ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.88 (br s, 1H), 8.58 (s, 1H),
7.96 (d, J = 8.2 Hz, 1H), 7.83–7.79 (q, J = 13.8, 5.8 Hz,
2H), 7.56–7.46 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t,
J = 7.6 Hz, 1H), 3.22 (q, J = 13.2, 4.2 Hz, 2H), 2.61 (q,
J = 12.4, 6.8 Hz, 2H), 1.24 (q, J = 12.4, 6.8 Hz, 2H),
1.21–1.04 (q, J = 14.8, 7.4 Hz, 6H), 0.78 (t, J = 7.4 Hz,
3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 173.1, 148.4,
128.4, 127.6, 125.2, 125.1, 124.8, 121.8, 108.2, 52.6, 30.1,
28.9, 28.4, 22.1, 18.8, 12.6; LC-MS m/z (%): 363 (M + H);
HPLC 99.4% RT 9.36 min; Anal. Calc. for
C18H22N2O2S2: C, 59.64; H, 6.12; N, 7.73; S, 17.69;
Found C, 59.63; H, 6.13; N, 7.74; S, 17.68.
3.4 | Biological evaluation
All the synthesized compounds were tested for their in vitro
anticancer activity against various cancer cell lines. The anti-
cancer activity test was performed according to the proce-
dure developed by the National Cancer Institute (NCI, USA)
in the “In vitro Anticancer Drug Discovery Screen,” which
uses the protein-binding dye sulforhodamine B (SRB) to
assess cell growth.[32,33] Briefly, cells were grown in 96-well
plates in suspension and then exposed for 48 hr to five serial
concentrations of 1 × 10−7, 1 × 10−6, 1 × 10−5, 1 × 10−4
,
and 1 × 10−3 M of each compound. Cells were fixed and
stained with the protein-binding SRB stain. Excess stain was
washed, the bound stain was solubilized, and the absorbance
was measured at 492 nm using a plate reader. Inhibitory
concentration of the compounds that inhibited 50% of the
net cell growth (IC50) was calculated from the dose–
response curve obtained for each test compound and cell
line. The IC50 values are presented in micromolar (μM) con-
centration. Doxorubicin was used as positive control for the
comparison of cytotoxicity of the synthesized compounds.
Assays were performed in triplicate on three independent
experiments, and their mean values were taken as the final
reading. All the newly synthesized compounds 7a–7j and
8a–8j were evaluated for their anti-proliferative activities
against a panel of four different human cancer cell lines. The
results are summarized in Table 1. These values represent
the concentration required to inhibit 50% of the cell popula-
tion compared to the control cells treated with DMSO and
positive control doxorubicin under similar conditions. The
synthesized compounds were evaluated for their in vitro
anticancer activity against the human lung cancer cell line
(A549), cervical (HeLa) cancer cell line, breast cancer cell
line (MCF-7), and prostate cell line (DU-145). The cell line
activity study results are explained below.
3.3.17
| N-(Naphtho[2,3-d] thiazol-2-yl)octane-
1-sulfonamide (8g)
Off-white solid; yield 86%; m.p. 166–167ꢀC; 1H NMR
(400 MHz,DMSO-d6, ppm) δ 8.88 (br s, 1H), 8.58 (s, 1H),
7.96 (d, J = 8.2 Hz, 1H), 7.83–7.79 (q, J = 13.8, 5.8 Hz,
2H), 7.56–7.46 (m, J = 14.4, 7.2 Hz, 1H), 7.41 (t,
J = 7.6 Hz, 1H), 2.22 (q, J = 13.2, 4.2 Hz, 2H), 1.61 (q,
J = 12.4, 6.8 Hz, 2H), 1.38 (q, J = 12.4, 6.8 Hz, 2H),
1.18–1.04 (q, J = 14.8, 7.4 Hz, 8H), 0.81 (t, J = 7.4 Hz,
3H); 13C NMR (CDCl3, 100 MHz, ppm) = δ 171.1, 148.4,
128.4, 127.6, 125.2, 125.1, 124.8, 121.8, 108.2, 52.8, 30.6,
29.3, 28.4, 28.1, 22.2, 18.8, 12.8; LC-MS m/z (%):
377 (M + H); HPLC 98.8% RT 9.40 min; Anal. Calc. for
C19H24N2O2S2: C, 60.61; H, 6.42; N, 7.44; S, 17.03;
Found C, 60.62; H, 6.41; N, 7.43; S, 17.02.
3.3.18
| N-(Naphtho[2,3-d] thiazol-2-yl)cyclopropane-
1-sulfonamide (8h)
1
Brown semisolid; yield 81%; H NMR (400 MHz,DMSO-
d6, ppm) δ 8.87 (br s, 1H), 8.59 (s, 1H), 7.96 (d, J = 8.2 Hz,
1H), 7.83–7.78 (q, J = 13.8, 5.8 Hz, 2H), 7.58–7.46 (m,
J = 14.4, 7.2 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 2.47 (m,
1H), 0.70–0.86 (q, J = 14.8, 7.4 Hz, 4H); LC-MS m/z (%):
305 (M + H).
For lung cancer cell line (A549), the compounds 7a, 7d,
and 8d were most active with IC50 values of 3.65, 3.88, and

PAWAR ET AL.
7
TABLE 1 In vitro anticancer screening of the synthesized compounds
TABLE 2 Inhibitory activity of selected compounds against panel of eight
against four cell lines
human kinases
Sr. no.
7a
A-549a
HeLab
MCF-7c
DU-145d
7d
(% Inh.)
7e
(% Inh.)
8a
(% Inh.)
8d
(% Inh.)
8e
(% Inh.)
Kinase
3.65 Æ 0.12
4.12 Æ 0.13
4.10 Æ 0.21
3.88 Æ 0.11
4.12 Æ 0.08
8.18 Æ 0.11
13.12 Æ 0.24
6.13 Æ 0.18
9.27 Æ 0.08
11.73 Æ 0.22
4.46 Æ 0.16
6.11 Æ 0.11
5.78 Æ 0.18
3.12 Æ 0.08
8.17 Æ 0.16
11.17 Æ 0.12
12.11 Æ 0.11
11.80 Æ 0.06
6.15 Æ 0.12
7.13 Æ 0.06
1.71 Æ 0.18
4.81 Æ 0.16
6.81 Æ 0.08
4.11 Æ 0.04
3.82 Æ 0.22
3.78 Æ 0.06
9.13 Æ 0.08
11.23 Æ 0.12
8.72 Æ 0.08
11.37 Æ 0.12
16.43 Æ 0.08
6.28 Æ 0.16
3.78 Æ 0.11
3.12 Æ 0.17
2.78 Æ 0.12
2.74 Æ 0.08
13.12 Æ 0.04
6.11 Æ 0.17
8.81 Æ 0.11
11.12 Æ 0.12
8.12 Æ 0.08
1.82 Æ 0.06
8.13 Æ 0.06
11.13 Æ 0.22
6.15 Æ 0.06
2.81 Æ 0.12
4.18 Æ 0.12
7.17 Æ 0.06
16.14 Æ 0.11
10.78 Æ 0.08
13.17 Æ 0.11
NA
13.17 Æ 0.16
16.11 Æ 0.12
9.11 Æ 0.12
3.78 Æ 0.11
6.12 Æ 0.22
12.11 Æ 0.04
NA
Aurora-A
Aurora-B
CDK2/cyclinA
CDK2/cyclinE
CDK5/P25
EGFR
65
68
38
17
26
12
34
13
64
70
37
12
38
11
38
21
31
61
43
21
41
17
36
9
63
56
37
22
44
31
38
21
61
67
43
23
36
15
36
9
7b
7c
7d
7e
7f
7g
mTOR
7h
7i
15.16 Æ 0.06
18.43 Æ 0.08
NA
PDK1
7j
8a
7.11 Æ 0.16
7.68 Æ 0.12
9.43 Æ 0.08
3.74 Æ 0.06
8.11 Æ 0.18
14.13 Æ 0.16
13.17 Æ 0.08
7.61 Æ 0.22
12.13 Æ 0.16
4.14 Æ 0.32
1.91 Æ 0.08
3.12 Æ 0.08
8.12 Æ 0.11
3.78 Æ 0.18
4.76 Æ 0.04
7.72 Æ 0.06
12.17 Æ 0.08
NA
inactive and that compounds with butyl and pentyl sulfon-
amides were the most active compared to other synthesized
compounds in both series. The compounds with cyclopropyl,
cyclobutyl, and cyclopentyl were moderate to less active in
both series of compounds. The compounds 7d, 7e, 8a, 8d,
and 8e were the most active in all cell lines studied, so we
further tested them for their activity against a panel of eight
human kinases at 10 μM concentration. The inhibition
results are summarized in Table 2.
The compounds 7d, 7e, 8d, and 8e showed 65, 64,
63, and 61% inhibition, respectively, for aurora-A kinase.
For aurora-B kinase, the compound 7e showed 70% inhibi-
tions, along with the remaining compounds 7d (68%), 8a
(61%), 8d (56%), and 8e (67%) inhibitions. For CDK/cy-
clinA, CDK/cyclinE, CDK5/P25, EGFR, mTOR, and
PDK1, the inhibition was in the range 9–44% for com-
pounds7d, 7e, 8d, and 8e. For mTOR kinase, the inhibition
was in the range 34–38% for compounds 7d, 7e, 8d, and 8e.
For PDK1 kinase, the inhibition for all compounds was very
low, being in the range 9–21%. The active compounds in the
cell line data were most active for the inhibition of aurora-A
and aurora-B human kinases.
8b
8c
8d
8e
8f
8g
8h
8i
5.98 Æ 0.18
9.11 Æ 0.04
6.11 Æ 0.06
1.62 Æ 0.12
8j
Doxor.
Notes: Data are expressed as IC50 (μM) Æ SD (n = 3). IC50: The concentration
required to inhibit 50% of cell population.
a
A-549: Human lung cancer cell line.
HeLa: Human cervical cancer cell line (ATCC No. CCL-2).
MCF-7: Human breast cancer cell line.
DU-145: Human prostate cancer cell line.
b
c
d
3.12 μM respectively. Compounds 7b, 7c, 7e, 8a, 8c, and 8i
were moderately active with IC50 values in the range
4.10–6.15 μM, while the remaining compounds were less
active or inactive.
For the HeLa cell line, the compounds 8d and 8e were
the most active with IC50 values of 2.78 and 2.74 μM,
respectively. Compounds 7a, 7c, 7d, 7e, 8b, and 8c were
moderately active with IC50 values is in the range
3.12–4.81 μM, while the remaining compounds were very
less active or inactive.
For the MCF-7 cell line, compound 7d was the most
active with the IC50 value of 2.81 μM. The compounds 7e,
8d, and 8j were moderately active with IC50 values of
3.74–4.18 μM, while the remaining compounds were much
less active or inactive.
For the Du-145 cell line, compounds 7d, 8a, 8c, and 8d
were moderately active whereas the remaining compounds
were mostly inactive. Compound 8a was the most active for
the Du-145 cell line with the IC50 value of 3.12 μM, but it
was only moderately active for the remaining cell lines. Sim-
ilar results were obtained for the compound 8c for the cell
lines MCF-7 and Du-145, whereas most of the compounds
were inactive for A-549 and HeLa. From the SAR, it can be
concluded that compounds having methyl, ethyl, propyl,
heptyl, and octyl sulfonamides were moderately active to
4
| CONCLUSIONS
We synthesized two series of compounds N-(benzo[d]
thiazol-2-yl)substituted-1-sulfonamide (7a–7j) and N-
(naphtho[2,3-d] thiazol-2-yl)substituted-1-sulfonamide (8a–
8j) from aniline and naphthalene-2-amine, respectively,
through a series of reactions including thiazol synthesis and
sulfonamide coupling. They showed simple reaction condi-
tions, easy work-up, short reaction times, and good to high
yields. The synthesized compounds were screened for anti-
cancer activity against MCF-7, HeLa, A-549, and Du-145
cancer cell lines. Most of the compounds were active for the
tested cell lines with IC50 values in the range
2.74–18.43 μM. The compounds 7d, 7e, 8a, 8d, and 8e were
the most active with IC50 values in the range 2.74–8.17 μM.
The compounds 7d, 7e, 8a, 8d, and 8e showed promising
inhibitions (>55%) for aurora-A and aurora-B human
kinases.

8
PAWAR ET AL.
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ACKNOWLEDGMENT
The authors are thankful to the Head, Department of Chemi-
cal Technology, Dr. Babasaheb Ambedkar Marathwada Uni-
versity, Aurangabad, Maharashtra 431004, India, for
providing the laboratory facilities.
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How to cite this article: Pawar CD, Chavan SL,
Pawar UD, Pansare DN, Deshmukh SV, Shinde DB.
Synthesis, anti-proliferative activity, SAR, and kinase
inhibition studies of thiazol-2-yl- substituted sulfon-
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