Copper fluorapatite assisted synthesis of new 1,2,3-triazoles bearing a benzothiazolyl moiety and their antibacterial and anticancer activities

Article abstract of DOI:10.1039/c9nj00377k

A series of new 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazoles and 2-(4-((4-(benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-phenylacetamides (5a-t) have been synthesized via a copper fluorapatite (CuFAP) catalysed click reaction. The compounds (5a-t) were synthesized using freshly prepared 2-aryl-4-hydroxybenzothiazole (1) as a starting material. 2-Aryl-4-hydroxybenzothiazole (1) was condensed with propargyl bromide (2) in N,N-dimethylformamide in the presence of potassium carbonate to obtain a key intermediate, benzothiazolyl phenoxymethylalkyne (3). This alkyne (3) was then separately subjected to subsequent click chemistry with freshly prepared aryl/benzyl azides and substituted 2-azido-N-phenylacetamides (4a-t) in the presence of copper fluorapatite (CuFAP) and triethyl amine and good to excellent yields of the title compounds (5a-t) were obtained. All the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR and HRMS analyses. All the synthesized compounds were found to be effective against human breast carcinoma (MCF-7) cells. Among them, compounds 5e, 5h, 5j, 5o and 5p were found to be strong inhibitors for the growth of MCF-7 cells with IC₅₀ values of 10.14, 9.84, 10.06, 10.13 and 9.19 μg mL^-1, respectively. In addition, compounds 5a, 5c, 5d, 5e, 5f, 5k, 5n, 5o and 5q have shown activity against a multidrug resistant pathogenic strain of E. coli with MIC values of 7.99, 8.44, 8.11, 8.06, 8.54, 9.40, 8.02, 9.25 and 10.62 μg mL^-1, respectively.

Full text of DOI:10.1039/c9nj00377k

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Copper Fluorapatite assisted synthesis of new 1,2,3-triazolesDOI
b
: 1
e
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C9NJ00377K
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benzothiazolyl moiety and their antibacterial and anticancer activities
a
a
b
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Sambhaji T. Dhumal, Amarsinh R. Deshmukh, Kiran R. Kharat, Bhaskar R. Sathe,
c
a*
Santosh S. Chavan, Ramrao A. Mane
aDepartment of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad,
31004, India.
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bCentre for Advanced Life Sciences, Deogiri College, Aurangabad- 431005, India.
cChemistry and Chemical Bioengineering Unit, Okinawa Institute of Science and Technology
Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495 (Japan).
*
Corresponding Author: manera2011@gmail.com (Dr. Ramrao A. Mane)
Abstract:
A series of new 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]
thiazoles and 2-(4-((4-(benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-
phenylacetamides (5a-t) has been synthesized via Copper Fluorapatite (CuFAP) catalysed
click reaction. The compounds (5a-t) were synthesized using freshly prepared 2-aryl-4-
hydroxybenzothiazole (1) as a starting material. 2-Aryl-4-hydroxybenzothiazole (1) was
condensed with propargyl bromide (2) in N,N-dimethylformamide in the presence of
potassium carbonate to obtain a key intermediate, benzothiazolyl phenoxymethylalkyne (3).
This alkyne (3) was then separately subjected following click chemistry with freshly prepared
aryl/benzyl azides and substituted 2-azido-N-phenylacetamides (4a-t) in presence of Copper
fluorapatite (CuFAP) and triethyl amine and obtained better to excellent yields of the titled
1
compounds (5a-t). All the newly synthesized compounds were characterized by IR, H NMR,
13C NMR and HRMS analyses. All the synthesized compounds were found to be effective
against human breast carcinoma (MCF-7) cells. Among them, compounds 5e, 5h, 5j, 5o and
5
p were found to be strong inhibitors for the growth of MCF-7 cells with IC values 10.14,
50
9.84, 10.06, 10.13 and 9.19 µg/mL, respectively. In addition, compounds 5a, 5c, 5d, 5e, 5f,
k, 5n, 5o and 5q have shown activity against the multidrug resistant pathogenic strain of
5
E.coli with MIC values 7.99, 8.44, 8.11, 8.06, 8.54, 9.40, 8.02, 9.25 and 10.62 µg/mL,
respectively.
Keywords
Copper Fluorapatite, 1,2,3-Triazole, 2-Arylbenzothiazole, Click Chemistry, Anticancer
Activity, Antibacterial Activity, ADME Prediction.

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1
. Introduction
1
,2,3-triazoles are five membered N-heterocyclic compounds and are featured in a
1
large number of bioactive molecules and medicinal chemistry. Among the various 1,2,3-
triazoles, 1,4-disubstituted-1,2,3-triazole derivatives have been found to have broad spectrum
applications in different areas such as bioconjugations, polymers, pesticides, supramolecular
chemistry, pharmaceuticals and surface sciences.2-5 Triazoles act as effective surrogates in
bioactive molecules because they are capable to exhibit hydrogen bonding, dipole-dipole
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moments and π-stacking interactions. They are also used as a linkers and show bioisosteric
effects on peptide linkage, aromatic rings, imidazoles and double bonds.7,8 These
aforementioned features of triazoles are found to be responsible for their therapeutic
significance in medicinal chemistry as they bind with biological targets with high affinity and
have improved solubility.9
Literature survey revealed that, 1,4-disubstituted-1,2,3-triazole derivatives are
endowed with numerous therapeutic activities such as antifungal,10 antibacterial,11
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antitubercular, antidiabetic, anticancer, anti-HIV, antileishmanial and antiviral. In
recent years, triazole has been gaining special attention in the drug discovery because the
drugs bearing 1,2,3-triazole scaffold viz tazobactum, cephalosporin and cetatrizine are
clinically used against bacterial infections.18 While triazole bearing medicaments like
fluconazole, itraconazole, voriconazole and ketoconazole are widely used as antifungal
agents.19
Benzothiazole is a privileged fused heteroatomic compound containing sulphur and
nitrogen as heteroatoms. Benzothiazoles are emerged as key scaffolds for new drugs
2
0
discovery because of their inherent affinity for diverse biological receptors. Benzothiazole
and its derivatives offer high degree of structural diversity that has proven their usefulness
2
1
for searching new therapeutic leads. Benzothiazole containing compounds are gaining
immense importance due to the broad spectrum of pharmacological activities such as
2
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antimicrobial, anticancer, antitubercular, antifungal, antidiabetic, antiinflammtory
and antiviral.28
Physical, metabolic, chemical and genetic conditions are mainly responsible for the
growth of the malignant cells. Breast cancers are the malignancies in mammary gland cells
29
30
in women. Several factors make women at high risk of the breast cancer. The use of
various therapies like radiations, surgical removal and chemotherapeutic drugs can reduce
invasive breast cancer. However due to harmful side effects of the radio/chemotherapy the

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patients are found to remain traumatized.31,32 The search for target-specific and less side-
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DOI: 10.1039/C9NJ00377K
effect cancer therapy is still undergoing. Owing to the therapeutic significance of
benzothiazoles and 1,2,3-triazoles, in recent years a library of thiazole/benzothiazole
derivatives conjugated with 1,2,3-triazole (Fig. 1) has been synthesized and the conjugates
are found to possess antibacterial and anticancer activities. Benzothiazole based 1,2,3-
triazole 1 has displayed potent anticancer activity against Colo-205 and A549 cells.33
Whereas thiazole substituted 1,2,3-triazole 2 has exhibited potent anticancer activity against
leukemia K-562 and SK-MEL-5 cell lines.34 Recently reported thiazoles/benzothiazoles
coupled with 1,2,3-triazole 3-4 have been reported for their antibacterial and antitubercular
activities.35-36
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O
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S
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CF3
F
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NH
N
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Figure 1. 1,2,3-Triazoles containing bioactive molecules
Literature reveals that triazoles possessing benzothiazolyl scaffold have displayed
remarkable anticancer and antibacterial activities. It has been also revealed that triazoles
possessing 4-benzothiazolyl phenoxymethyl moiety has not been reported. Keeping this in
view and in a search of better anticancer and antibacterial new therapeutics here it has been
thought worthwhile to design and synthesize the titled compounds, 2-(4-((1-phenyl-1H-1,2,3-
triazol-4-yl)methoxy)phenyl)benzo[d]thiazoles
and
2-(4-((4-(benzo[d]thiazol-2-
yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-phenylacetamides (5a-t) by developing a
convenient and novel synthetic protocol from readily available 2-aryl-4-hydroxy
benzothiazole.
In view of the wide applications of 1,2,3-triazoles, there is an extensive interest in
developing novel synthetic methods for their constructions. The conventional way to
synthesize 1,2,3-triazoles is by following Huisgen 1,3-dipolar cycloaddition of alkynes with

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DOI: 10.1039/C9NJ00377K
organic azides. This cycloaddition normally requires high temperature and long reaction
time and affords a mixture of 1,4 and 1,5-regioisomers. To overcome the above difficulties,
most popular “click chemistry approach”, for the synthesis of exclusively 1,2,3-triazoles has
been developed by Sharpless and co-workers38 and independently by Meldal and co-
workers.39 Copper-catalyzed alkyne-azide cycloaddition (CuAAC) has been become a
classical protocol for getting 1,4-disubstituted 1,2,3-triazoles as a sole regioisomer.
Numerous successful examples have been reported in the literature for the preparation of
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1
,2,3-triazoles using CuSO .5H O and sodium ascorbate, copper nanoparticles, copper
4 2
oxide nanoparticles,42 copper supported on graphene oxide,43 cellulose supported copper
nanoparticles,44 copper nanoparticles supported on silica coated maghemite,45 copper
4
6
47
nanoparticles supported on charcoal and copper ferrite nanoparticles.
It is also revealed from literature that, apatites are emerging as accelerators for
4
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carrying various value added transformations. Apatites are found in nature or derived from
minerals. Hydroxy calcium apatites and fluoro calcium apatites are most commonly used
4
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apatites having general formula, Ca10 (PO ) X (X=OH,F). These are found to be well
4 6
2
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explored as catalysts for rapidly conducting various organic transformations. Since last few
decades, copper hydroxyapatite and copper fluorapatite (CuFAP) have been introduced as
stable and safer heterogeneous catalysts for carrying condensations/cyclocondensations and
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various other organic transformations such as- O-aryloxime ethers, N-arylation, and C-N
5
3
bond formation. CuFAP has ability to adsorb organic, organometallic molecules and salts
on their surface.54
Literature survey also revealed that existing synthetic protocols, used for obtaining
1
,2,3-triazoles by carrying cycloaddition of alkynes and azides are having one or other kind
of limitations. Continuous efforts are found to be directed for performing the cycloaddition
efficiently by incorporating safer and suitable recyclable catalysts, replacing
CuSO /Cu(OAc) and reducing agent. Considering the significance of Ca/Cu apatites as
4
2
recyclable catalysts, recently Cu (II) hydroxyapatite has been applied not only for carrying O-
arylation or N-arylation but also for accelerating the rate of cycloaddition of azides and
5
5
alkyne for getting 1,2,3-triazoles. It has also been observed that the use of CuFAP has not
been attempted in carrying the cycloaddition under discussion. CuFAP is most stable and
5
6
having more advantage as a catalyst than that of copper hydroxyapatite. Keeping the above
observations in mind here first time strategy has been adopted to incorporate CuFAP in
catalysing cycloaddition of azides and new alkyne for obtaining high yields of 1,2,3-triazoles
(5a-t).

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2
. Results and Discussion
2
.1 Chemistry
The desired compounds, new 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)
benzo[d]thiazoles and 2-(4-((4-(benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-
yl)-N-phenylacetamides (5a-t) have been synthesized starting from freshly prepared 2-aryl-4-
hydroxybenzothiazole (1). 2-Aryl-4-hydroxybenzothiazole (1) was allowed to interact with
propargyl bromide (2) in DMF in the presence of K CO at room temperature for 2h to obtain
1
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a key intermediate, benzothiazolyl phenoxymethyl alkyne (3). Then cycloaddition of this
intermediate, benzothiazolyl phenoxymethyl alkyne (3) was separately carried with various
azides (4a-t) in the presence of CuFAP and triethyl amine and obtained the desired products,
2-(4-((1-phenyl/benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazoles and 2-(4-
(
(4-(benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-phenylacetamides (5a-
t), respectively with better to excellent yields.
1
13
All the newly synthesized compounds were characterized by IR, H NMR, C NMR
and HRMS techniques. The IR spectrum of compound (5a) indicates the formation of product
-1
as it shows a characteristic absorption peaks at 1466 and 1400 cm which correspond to the
1
N-N and N=N stretching, respectively. The H NMR spectrum of compound (5a) displays
peaks, a singlet at  5.40 ppm, due to the OCH and a multiplet in the region 7.13 to 8.10 ppm
2
due to the merged signals of triazolyl ring-H and 13 aromatic-H. The presence of three
1
3
characteristics carbon signals are observed at 62.31, 115.41 and 167.80 ppm in C NMR
spectrum of compound (5a). The signal of carbon at 62.31 ppm due to the OCH group
2
whereas carbon signals at 115.41 and 167.80 ppm due to the triazolyl ring carbon and
thiazolyl ring carbon, respectively, confirming the presence of a 1,2,3-triazole ring in (5a).
The HRMS spectrum further strengthen the structure assigned to (5a) as 2-(4-((1-phenyl-1H-
+
1
,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole, showing [M+H] ion peak at m/z
385.1132 for its molecular formula C H N OS. Experimental procedures and spectra of
2
2
16
4
1
,2,3-triazoles (5a-t) and intermediates are given in supplementary data. The synthetic
sequence is depicted in Scheme 1.

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S
N
OH
Br
(
1)
(2)
N3
N3
DMF K CO ,
2
3
R1
R2
R1
R2
rt
4h
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(4k-o) R3
R3
(
4a-j)
S
O
CuFAP, DCM
rt, 1h
CuFAP, DCM
rt, 1h
N
(
3)
S
N
S
N
N
N
N
O
N
O
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O
N3
HN
CuFAP
R1
DCM, rt,
R1
R3
(
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(5k-o)
1h
R2
R1
R2
R3
R3
R2
(
4p-t)
S
N
O
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N
N
O
NH
(
5p-t)
R1
R2
R3
1
2
3
1
2
3
1
2
3
1
2
3
5
5
5
a=R =H, R =H, R =H
5f=R =H, R =Br, R =H
5k=R =H, R =H, R =H
5p=R =H, R =H, R =H
1
3
1
2
3
1
2
3
1
2
3
2
5q=R =H, R =Cl, R =H
b=R =Cl, R =H, R =H
5g=R =OCH3, R =H, R =H
5l=R =H, R =H, R =F
1
2
3
1
2
3
1
2
3
1
2
3
c=R =H, R =Cl, R =H
5h=R =H, R =H, R =OCH
5m
=R =Cl, R = , R =H
H
5r=R =H, R =H R =Cl
3
1
2
3
1
2
3
1
2
3
1
2
3
5
d=R =H, R =H, R =Cl
5i=R =F, R =H, R =F
5n=R =H, R =Cl, R =H
5s=R =H, R =CH , R =H
3
1
2
3
1
2
3
1
2
3
1
2
3
5
e=R =Br, R =H, R =H
5j=R =CH , R =CH R =CH
5o
=R =H, R =H, R =Br
5t=R =H, R =H, R =CH
3
3
3,
3
Scheme 1. Synthetic route for 1,2,3-triazole coupled benzo[d]thiazole derivatives (5a-t).
In the present work freshly prepared azides (4a-t) have been cyclo added on freshly
prepared alkyne (3) using CuFAP as reusable catalyst. Attempts were made to provide right
reaction conditions for the cycloaddition. In search of right conditions, the model reaction has
been performed by varying amount of CuFAP catalyst, media and bases. Here we performed
cyclocondensation of a new benzothiazolyl phenoxy methyl alkyne (3) with phenyl azide (4a)
as a model reaction in the presence of CuFAP and triethylamine at room temperature to
obtain 5a. This model reaction was performed under identical condition in different solvents.
The screening results of the model reaction run in different solvents at rt in the presence of
CuFAP are recorded in Table 1, entry 1-12. Among the screened solvents, DCM was found
to be the best solvent to afford product 5a.

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DOI: 10.1039/C9NJ00377K
To optimise the amount of CuFAP, required to carry the model cycloaddition, we
attempted the cycloaddition in DCM by varying amounts of CuFAP from 25 mg to 100 mg
using alkyne (3) (0.0004 mol), phenyl azide (4a) (0.0004 mol) and triethyl amine (0.0004
mol). It was observed that high yield of 2-(4-((1-aryl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)
benzo[d]thiazole (5a) was obtained, when the model reaction was performed in the presence
of 50 mg catalyst using 0.0004 mole initial concentration of each of the reactant (Table 2,
entry 1-4). The cyclocondensation was found to be completed within 1h giving 94 % yield of
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
,2,3-triazole (5a). Therefore, 50 mg of CuFAP catalyst was selected as the optimal quantity
for the reaction (Table 2). To investigate the role of the CuFAP, the cycloaddition was
performed under identical conditions in the absence of CuFAP and observed that reaction did
not proceed even when constantly stirred at rt for more than 30 h. This observation clearly
indicated that here CuFAP has played key role in accelerating the rate of the cycloaddition.
Table 1. Screening of reaction media for the synthesis of compound 5a.a
b
Entry
Solvents
DCM
Time (h)
1h
Yields (%)
1
2
3
4
5
6
7
8
9
94
92
70
52
68
48
72
31
18
37
24
42
DMF
1h
DMSO
Isopropanol
MeOH
1h
1h
1h
PEG-400
CHCl3
1h
1h
1,4-Dioxane
THF
1h
1h
1
0
EtOH
1h
11
Toluene
1h
1
2
CH CN
1h
3
aReaction Conditions: Alkyne (3) (0.0004 mol), phenylazide (4a) (0.0004 mol), triethyl
b
amine (0.0004 mol), solvent (5 ml), CuFAP (50 mg), at room temperature, Isolated
yields.

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2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 2. Optimization of amount of CuFAP as catalyst, required for the cycloadditiona
View Article Online
DOI: 10.1039/C9NJ00377K
Entry
Catalyst concentration
Compound (Yield %b)
1
2
3
4
25 mg
50 mg
75 mg
100 mg
65
94
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
~94
~94
aReaction Conditions: Alkyne (3) (0.0004 mol), phenylazide (4a) (0.0004 mol), triethyl
b
amine (0.0004 mol), solvent (5 ml) at room temperature, Isolated yields.
The model reaction was performed under identical conditions as above by varying
organic and inorganic bases, keeping their initial concentration same. The results were
recorded in Table 3 and noted that model reaction gave highest yield of reaction product 5a,
when run in the presence of triethyl amine than the other bases. Keeping all the above
observations in mind, the model reaction was performed under optimised conditions i.e. using
0.0004 mol of initial concentration of each reactant and base, triethyl amine and carrying
reaction in DCM (10 ml) in the presence of 50 mg of CuFAP with stirring for 1h at rt and
obtained 94% yield of 5a. Using the above optimised conditions, various titled reaction
products (5a-t) have been synthesized with better to excellent yields, starting from respective
azides (4a-t) and alkyne (3).
Table 3. Screening of the bases
Entry
Base
Time (h)
Yield (%)
1
2
3
Triethyl amine
1h
1h
1h
94
74
91
Dimethylamine
N,N-diisopropylamine
4
5
6
7
8
DABCO
DBU
1h
1h
1h
1h
1h
61
76
K CO
34
2
3
CS CO
67
2
3
Without base
Trace
aReaction Conditions: Alkyne (3) (0.0004 mol), phenylazide (4a) (0.0004 mol), DCM (5
b
ml), CuFAP (50 mg), Bases (0.0004 mol) at room temperature, Isolated yields.
Owing to the environmental concern the development of heterogeneous recyclable
catalyst are in high demands in worldwide. Hence the having established efficiency of the
CuFAP catalyzed 1,3 dipolar cycloaddition reactions, then we investigated the recyclability

Page 9 of 27
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and reusability of catalyst for the synthesis of triazoles (5a-t) from alkyne (3) with
phenylazide (4a) under standard reaction condition, and results are shown in Table 4. The
Copper fluorapatite catalyst can be used to next turn without loss of significant activity. This
cycloaddition proceeded very smoothly and afforded the titled triazoles (5a-t) with excellent
yield. (Table 4, entries 2-5).
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 4. Recoverability and reusability of CuFAP catalyst.a
(Yield%b)
Entry
Run
1
2
3
4
5
Fresh
Run-1
Run-2
Run-3
Run-4
95
94
94
90
90
aReaction Conditions: Alkyne (3) (0.0004 mol), phenylazide (4a) (0.0004 mol), DCM (5
b
ml), CuFAP (50 mg), Et N (0.0004 mol) at room temperature, Isolated yields
3
On the basis of the above presented experimental results and the previous literature
5
7
reports on the CuFAP catalyst, a probable reaction mechanism indicating the role of CuFAP
in rate acceleration of 1,3 dipolar cycloaddition, leading to triazoles has been presented in
Scheme 2. Initially, the triethyl amine abstracts the proton from alkyne, and insitu generated
nucleophile then reacts with CuFAP catalyst to generate the intermediate complex (I). The
corresponding complex (I) undergoes addition on phenyl azide to form intermediate complex
(
II), which is subsequently interconverted to give complex (III). The unstable complex (III)
rapidly breaks, forming stable 1,2,3-triazole (IV) and CuFAP, catalyst in its original form.
Ph
H
O
N N
II
Cu
P
P
N
O
O
(II)
Ph-N3
R
Ph
H
O
H
O
N N
II
Cu
P
P
II
Cu
CuFAP
DCM
P
P
N
O
Et N
3
O
R
O
O
O
R
(III)
(
I)
R
N
N
N
O R
CuFAP
Ph
(IV)
Scheme 2. Plausible reaction mechanism of 1,3 dipolar cycloaddition reaction over CuFAP
catalyst for the synthesis of 1,2,3-triazoles (5a-t).

New Journal of Chemistry
Page 10 of 27
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8
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
View Article Online
DOI: 10.1039/C9NJ00377K
2
.2 Biological Evaluation
2.2.1 Analysis of the antiproliferative action of compounds on human breast cancer cells
The anticancer potential of the synthesized compounds (5a-t) was evaluated in vitro
against Human breast cancer (MCF-7) cells. The effect of the compounds on the MCF-7 cells
growth was observed. The MCF-7 cells were exposed to the compounds for 24 h with
concentration ranges from 9 µg/mL to 120 µg/mL. The Paclitaxel was used as standard
reference anticancer drug. It is evident from Table 5 that the most of synthesized compounds
have shown excellent action as anticancer compounds compared to standard drug, Paclitaxel.
Among the newly synthesized compounds 5b, 5c, 5e, 5h, 5j, 5m, 5n, 5o, 5p, 5q, 5r, 5s and
5t were found to be more effective for inhibition of growth of the MCF-7 cells (Fig. 2). The
compound 5p have phenyl acetamido moiety shown promising anticancer action on MCF-7
cells (IC 9.19 µg/ml). The compound 5h with 4-methoxy substituted benzene ring has also
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
0
displayed notable inhibitory activity with IC 9.84 µg/mL. The compounds 5j and 5e have
5
0
2
7
,4-difluoro and 2-bromo substituted benzene ring, respectively found effective against MCF-
cells with IC 10.06 and 10.14 ug/mL. In addition to this, compounds 5b (IC =18.9), 5c
5
0
50
(
IC =12.39), 5m (IC =12.91), 5n (IC =12.59), 5o (IC =10.14), 5q (IC =12), 5r
50 50 50 50 50
(IC =11.04), 5s (IC =13.07) and 5t (IC =14.4) were found to be strong inhibitors for the
5
0
50
50
growth of MCF-7 cells (Fig. 2). The compounds with phenyl acetamido ring and 4-methoxy
substituted benzene ring are inducing death in MCF-7 cells. Benzothiazoles act via
competing with ATP for binding at the catalytic domain of tyrosine kinase. These compounds
may act into the hydrophobic pockets of EGFR tyrosine kinase.58
Table 5. The IC values of compounds (5a-t)
5
0
Compounds
IC50
-1
(ug.mL )
57.4
5
a
5
b
18.9
5
c
12.39
120.7
10.14
27.78
Na
5d
5
e
5
f
5
g
5h
9.84
5
i
40.45

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5
j
10.06
20.51
30.26
12.91
12.59
10.14
9.19
5k
5
l
5
m
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
n
5o
5
5
p
q
12
5
r
11.04
13.07
14.4
5s
5
t
IC = Concentrations of drug that decrease viability of the cell by 50 % compared to
5
0
untreated control cell. The values are the mean of IC of triplicate experiment.
5
0
Figure 2. Antiproliferative action of 1,2,3-triazoles (5a-t) on Human Breast cancer cells
(MCF-7 cells).

New Journal of Chemistry
Page 12 of 27
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
View Article Online
2
.2.2 Antimicrobial action of 1,2,3-triazoles (5a-t)
To determine the antimicrobial activity of each compound, antibacterial assay was
performed. The pathogenic bacterial cultures were exposed to the compounds (concentration
to 50 microgram/mL). All the newly synthesized compounds (5a-t) were screened for their
DOI: 10.1039/C9NJ00377K
0
0
1
2
3
4
5
6
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8
9
0
1
2
3
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
antimicrobial activity against multidrug resistant pathogenic strains of E.coli. We found that,
nine compounds viz. 5a, 5c, 5d, 5e, 5f, 5k, 5n, 5o and 5q were found to display potent
activity against multidrug resistant pathogenic strain of E.coli as compared to the standard
reference drug, Tetracyclin. Compound 5a bearing phenyl ring was found to be the most
potent with MIC 7.99 µg/mL. The compound 5n with 3-chloro benzyl moiety has shown
potent activity with MIC 8.02 µg/mL. The compounds 5e (MIC 8.06), 5d (MIC 8.11), 5c
(
MIC 8.44) and 5f (MIC 8.54) were having 2-bromo, 3-chloro, 4-chloro, 3-bromo
substituents on phenyl, respectively. Other compounds 5k, 5o and 5q have displayed
potential activity with MIC 9.40, 9.25, 10.62 µg/mL, respectively (Fig. 3). Similarly, the
compounds 5r, 5s and 5t were also found to be active against the E.coli (Fig. 3).
Figure 3. Inhibition of growth of multidrug resistant Escherichia coli by using 1,2,3-triazoles
(5a-t).

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2
.2.3 In silico ADME prediction:
Good efficacy and an acceptable ADME (absorption, distribution, metabolism and
excretion) profile are the most important properties of any successful drug. ADME properties
prediction is one of the widely known pharmacokinetic parameter for the prediction of the
oral bioavailability of any drug. Therefore, here we predicted the in silico ADME properties
of newly synthesized compounds (5a-t) and results are incorporated in Table 6.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 6. Pharmacokinetic parameters for in silico ADME prediction of 1,2,3-triazoles (5a-t).
b
MVd
MWe
miLogf
Entry
%
ABS
TPSA
(A )
n-
RO
TB
n-
ON
n-
Lipinski
violations
Drug
likeness
model
score
a
2
g
i
c
OH
NHh
Rule
-
-
-
-
<500
≤ 5
<10
5
<5
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
≤ 1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
-
5
a
90.77
90.77
90.77
90.77
90.77
90.77
87.58
87.58
90.77
90.77
90.77
90.77
90.77
90.77
90.77
80.73
80.73
80.73
80.73
80.73
52.84
52.84
52.84
52.84
52.84
52.84
62.08
62.08
52.84
52.84
52.84
52.84
52.84
52.84
52.84
81.94
81.94
81.94
81.94
81.94
5
5
5
5
5
5
6
6
5
5
6
6
6
6
6
7
7
7
7
7
331.66
345.19
345.19
345.19
349.54
349.54
357.20
357.20
341.52
381.34
348.46
353.39
362.00
362.00
366.34
393.38
393.38
393.38
396.41
396.41
384.46
418.91
418.91
418.91
463.36
463.36
414.49
414.49
420.44
426.55
398.49
416.48
432.94
432.94
477.39
475.96
475.96
475.96
455.54
455.54
5.37
6.21
6.24
6.05
6.34
6.37
5.59
5.43
5.84
7.00
5.69
5.85
6.32
6.37
6.50
5.53
5.55
5.58
5.30
5.35
-0.30
-0.13
-0.19
-0.02
-0.43
-0.47
-0.39
-0.41
-0.47
-0.11
0.10
0.43
0.27
0.57
0.24
0.96
0.67
0.04
0.75
0.50
5
b
5
5
c
5
5
d
5
5e
5
5
f
5
5
g
6
5
h
6
5
i
5
5j
5
5
k
5
5
l
5
5
m
5
5
n
5
5o
5
5
5
p
q
7
7
5
r
7
5s
5t
7
7

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5
5
5
5
6
a
d
h
b
c
View Article Online
DOI: 10.1039/C9NJ00377K
Percentage Absorption; Topographical polar surface area; Number of rotatable bonds;
e
f
g
Molecular volume; Molecular Weight; Lipophilicity; No. of hydrogen bond acceptors;
i
No. of hydrogen bond acceptors; Number of violations.
In this study, we calculated molecular volume (MV), molecular weight (MW),
0
1
2
3
4
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9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
logarithm of partition coefficient (mi LogP), number of hydrogen bond acceptors (n-ON),
number of hydrogen bonds donors (n-OHNH), topological polar surface area (TPSA),
number of rotatable bonds (n-ROTB) and Lipinski’s rule of five59 of all the newly
synthesized compounds using Molinspiration online property calculation toolkit.60
A
compound is considered to be an orally active drug as well as obeys the Lipinski’s rule of
five if there is only one violation is observed out of the following four criteria’s: miLog P
(
octanol-water partition coefficient) ≤5, molecular weight ≤500, number of hydrogen bond
acceptors ≤10 and number of hydrogen bond donors ≤5. Other than this absorption (% ABS)
of all the derivatives of the series was calculated by formula,
%
ABS = 109-(0.345 × TPSA).61
In addition to this, the drug-likeness model score (a collective property of physico-chemical
properties, pharmacokinetics and pharmacodynamics of a compound is represented by a
numerical value) of each and every compound was computed by MolSoft software.62
It was observed from Table 6 that most of the predictions were found to be within the
acceptable range. All the synthesized compounds exhibited very good % ABS ranging from
8
0.73 to 90.77 %. Drug likeness score was also calculated in order to achieve biological
activity of compound. Most of the compounds from the synthesized series show positive drug
likeness score. All the results show that the compounds possess average to good potential for
the development as orally active drug molecule.
3. Conclusion
A series of new 1,2,3-triazoles bearing benzothiazolyl moiety were synthesized from
1
,3-dipolar cycloaddition reaction of alkyne 3 and various azides (4a-t) using Copper
Fluorapatite (CuFAP) as a catalyst. All the synthesized compounds were evaluated for their
in vitro antiproliferative activity against human breast carcinoma cells MCF-7. Most of the
compounds were found to be effective against human breast carcinoma cells MCF-7.
Compounds 5e, 5h, 5j, 5o and 5p were found as promising anticancer compounds against
MCF-7 cells with IC50 values 10.14, 9.84, 10.06, 10.13 and 9.19 µg/mL, respectively.
Whereas compounds 5a, 5c, 5d, 5e, 5f, 5k, 5n, 5o and 5q were found antimicrobial against

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the multidrug resistant pathogenic strain of E.coli with MIC values 7.99, 8.44, 8.11, 8.06,
8.54, 9.40, 8.02, 9.25 and 10.62 µg/mL, respectively.
4
. Experimental Section
1
1
1
1
1
1
1
1
1
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2
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.1. General
All reagents and solvents were obtained from commercial suppliers and used without
further purification. The Copper fluroapatite were prepared according to reported
procedures53 and prepared catalyst was tested by one example with standard reaction
condition of published paper. All the various azides were synthesized from the reported
63
procedures. Reactions were monitored by thin layer chromatography (TLC) on silica gel
1
plates (GF 254) using UV light to visualize the course of the reactions. H NMR spectra and
13C NMR spectra were respectively recorded at 300 MHz and 100 MHz spectrometer using
CDCl and DMSO-d as solvent at room temperature. Chemical shifts (δ) are reported in ppm
3
6
with TMS as internal standard. Abbreviations for signal couplings are: s, singlet; d, doublet; t,
triplet; m, multiplet. Routine monitoring of reaction was performed by TLC using 0.25 mm
E. Merck precoated silica gel TLC plates (60 F254).
4.1.1 Synthesis of Benzothiazolylphenoxy methyl alkyne (3)
A mixture of 4-(benzo[d]thiazol-2-yl)phenol (1) (0.0044 mol, 1 gm) and propargyl bromide
(
0.0048 mol, 0.52 gm) (2) was dissolved in DMF (10 ml) and to this solution K CO (0.0088
2 3
mol, 1.22 gm) was added. The reaction mass was stirred at room temperature for 2h. The
progress of the reaction was monitored by TLC. After 2 h, the reaction mass was poured on
ice cold water. The off white solid obtained was filtered, washed with water and crystallized
from ethanol.
o
-1
Yield: 74 %, M.P.: 122-124 C; Off White Solid; IR (KBr) ν cm : 3274 (Aromatic C-H
1
stretching), 2127 (C C stretching), 1601 (C=C stretching), 1241 (C-O stretching); H NMR
(
300 MHz, CDCl ) δ ppm = 2.57 (s, 1H, Alkynyl-CH), 4.77 (s, 2H, OCH ), 7.06-8.08 (m,
3
2
8
H, merged peaks, Ar-H).; 13C NMR (100 MHz, CDCl ) δ ppm = 55.78, 75.93, 77.86,
3
115.17, 121.42, 122.80, 124.78, 126.13, 127.15, 128.97, 134.78, 154.08, 159.62, 167.49;
+
+
HRMS (ESI) calcd. for C H NOS [M+H] : 266.0595; found 266.0630.
1
6
11
4
.1.2 General procedure for the synthesis of compounds (5a-t)

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DOI: 10.1039/C9NJ00377K
Benzothiazolyl phenoxymethyl alkyne (3) (0.0004 mol, 0.1 gm) and various azides (4a-t)
(0.0004 mol, 0.047 gm) were dissolved in DCM (5 ml). To this stirred solution CuFAP (50
mg) and triethyl amine (0.0004 mol, 0.056 ml) were added and stirring was continued at rt.
The progress of the reaction was monitored by TLC. After stirring for 1h, reaction mixture
was diluted with 10 ml DCM followed by filtration to recover the catalyst. The filtrate was
concentrated in vacuo to get the crude product, which was further purified by crystallization
to obtain 1,2,3-triazole product.
0
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.1.2.1 2-(4-((1-Phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole (5a)
o
-1
Yield: 94 %, M.P.: 168-171 C; White Solid; IR (KBr) ν cm : 3273 (Aromatic C-H
-1
1
stretching), 1599 (C=C stretching) 1466 (N-N stretching), 1400 cm (N=N stretching); H
NMR (300 MHz, CDCl )  ppm = 5.40 (s, 2H, CH ), 7.13-8.10 (m, 14H, merged signals, 13
3
2
1
3
Ar-H and triazolyl-H); C NMR (100 MHz, CDCl )  ppm = 62.31, 115.41, 120.82, 121.28,
3
1
21.72, 123.08, 125.07, 126.43, 127.29, 129.15, 129.40, 129.99, 135.09, 137.12, 154.39,
+
+
160.62, 167.80; HRMS (ESI) calcd. for C H N OS [M+H] : 385.1038; found 385.1132.
2
2
16
4
4
.1.2.2 2-(4-((1-(2-Chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole
(5b)
o
-1
Yield: 86 %, M.P.: 166-168 C; White Solid; IR (KBr) ν cm : 3124 (Aromatic C-H
1
stretching), 1593 (C=C stretching), 1481 (N-N stretching), 1420 (N=N stretching); H NMR
(
300 MHz, CDCl )  ppm = 5.36 (s, 2H, OCH ), 7.09-8.06 (m, 13H, merged signals, Ar-H
3
2
and triazolyl-H); 13C NMR (125 MHz, CDCl )  ppm = 62.17, 115.31, 118.69, 121.00,
3
121.06, 121.69, 123.04, 125.06, 127.29, 129.18, 129.37, 131.04, 135.02, 135.81, 137.85,
+
+
1
44.89, 154.30, 157.32, 160.45, 167.71; HRMS (ESI) calcd. for C H ClN OS [M+H] :
22 16 4
4
19.0689 and found 419.0745.
4.1.2.3 2-(4-((1-(3-Chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole
5c)
(
o
-1
Yield: 88 %, M.P.: 146-148 C; White Solid; IR (KBr) ν cm : 3097 (Aromatic C-H
1
stretching), 1594 (C=C stretching), 1481 (N-N stretching), 1399 (N=N stretching); H NMR
(300 MHz, CDCl )  ppm = 5.39 (s, 2H, OCH ), 7.11-8.07 (m, 13H, merged signals, Ar-H
3
2
and triazolyl-H); 13C NMR (125 MHz, CDCl )  ppm = 62.38, 115.47, 120.89, 121.80,
3
1
23.15,125.15, 126.50, 127.35, 129.23, 129.47, 130.06, 134.51, 134.70, 135.16, 135.30,

Page 17 of 27
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35.61, 135.80, 137.00, 137.19, 144.80, 154.45, 160.68; HRMS (ESI) calcd. for
DOI: 10.1039/C9NJ00377K
+
C H ClN OS [M+H] : 419.0689; found 419.0740.
2
2
16
4
4
.1.2.4 2-(4-((1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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5
5
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5
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0
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0
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0
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5
6
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8
9
0
1
2
3
4
5
6
7
8
9
0
(5d)
o
-1
Yield: 94 %, M.P.: 202-205 C; White Solid; IR (KBr) ν cm : 3056 (Aromatic C-H
1
stretching), 1596 (C=C stretching), 1480 (N-N stretching), 1420 (N=N stretching); H NMR
(
300 MHz, DMSO-d )  ppm = 5.40 (s, 2H, OCH ), 7.28 9.07 (m, 13H, merged signals, Ar-H
6
2
13
and triazolyl-H); C NMR (125 MHz, DMSO-d )  ppm = 61.97, 116.28, 122.61, 122.96,
6
123.23, 123.89, 125.88, 126.67, 127.27, 129.63, 130.62, 133.80, 134.97, 136.06, 144.36,
+
+
1
54.37, 161.15, 167.66; HRMS (ESI) calcd. for C H ClN OS [M+H] : 419.0689 and
22 16 4
found 419.0739.
4.1.2.5 2-(4-((1-(2-Bromophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole
5e)
(
o
-1
Yield: 87 %, M.P.: 133-136 C; White Solid; IR (KBr) ν cm : 3042 (Aromatic C-H
1
stretching), 1600 (C=C stretching), 1476 (N-N stretching), 1431 (N=N stretching); H NMR
(300 MHz, CDCl )  ppm = 5.41 (s, 2H, OCH ), 7.12-8.09 (m, 13H, merged signals, Ar-H
3
2
and triazolyl-H); 13C NMR (125 MHz, CDCl )  ppm = 62.02, 115.21, 118.51, 121.47,
3
1
22.81, 124.82, 124.95, 126.28, 127.00, 128.16, 128.47, 129.12, 131.26, 133.88, 134.80,
+
+
1
36.33, 137.40, 160.36, 164.64, 167.57; HRMS (ESI) calcd. for C H BrN OS [M+H] :
22 16 4
463.0183 and found 463.0770.
4
.1.2.6 2-(4-((1-(3-Bromophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole
(5f)
o
-1
Yield: 85 %, M.P.: 173-175 C; White Solid; IR (KBr) ν cm : 2914 (Aromatic C-H
1
stretching), 1599 (C=C stretching), 1485 (N-N stretching), 1418 (N=N stretching); H NMR
(
300 MHz, CDCl )  ppm = 5.40 (s, 2H, OCH ), 7.14-8.10 (m, 13H, merged signals, Ar-H
3
2
and triazolyl-H); 13C NMR (100 MHz, CDCl )  ppm = 62.04, 115.18, 119.07, 120.96,
3
121.55, 122.90, 123.38, 123.70, 124.92, 126.27, 127.17, 129.23, 131.33, 131.99, 134.70,
+
+
1
4
34.86, 137.80, 153.71, 154.17, 160.30; HRMS (ESI) calcd. for C H BrN OS [M+H] :
22 16 4
63.0183 and found 463.0214.

New Journal of Chemistry
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DOI: 10.1039/C9NJ00377K
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.1.2.7 2-(4-((1-(2-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]
thiazole (5g)
o
-1
Yield: 93 %, M.P.: 169-172 C; White Solid; IR (KBr) ν cm : 2913 (Aromatic C-H
1
stretching), 1595 (C=C stretching), 1469 (N-N stretching), 1422 (N=N stretching); H NMR
0
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(
300 MHz, CDCl )  ppm = 3.90 (s, 3H, OCH ), 5.39 (s, 2H, OCH ), 7.08-8.22 (m, 13H,
3
3
2
13
merged signals, Ar-H and triazolyl-H); C NMR (125 MHz, CDCl )  ppm = 55.91, 62.09,
3
112.16, 115.21, 117.92, 121.19, 121.45, 122.78, 124.79, 125.41, 125.81, 126.15, 126.84,
+
1
29.08, 130.18, 131.53, 134.78, 151.01, 153.90, 160.51, 167.71; HRMS (ESI) calcd. for
+
C H N O S [M+H] : 415.1184 and found 415.1243.
2
3
19
4
2
4
.1.2.8 2-(4-((1-(4-Methoxyphenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]
thiazole (5h)
o
-1
Yield: 91 %, M.P.: 184-186 C; White solid; IR (KBr) ν cm : 3135 (Aromatic C-H
stretching), 2880 (Aromatic C-H stretching), 1597 (C=C stretching), 1478 (N-N stretching),
1
1
444 (N=N stretching); H NMR (300 MHz, DMSO-d )  ppm = 3.74 (s, 3H, OCH ), 5.35 (s,
6
3
13
2
H, OCH ), 6.91-8.33 (m, 13H, merged signals, Ar-H and triazolyl-H); C NMR (100 MHz,
2
DMSO-d )  ppm = 55.21, 61.30, 114.08, 115.57, 120.89, 122.26, 122.54, 125.23, 126.62,
6
+
1
28.96, 131.48, 134.29, 142.11, 153.69, 156.91, 160.61, 163.67, 167.10; HRMS (ESI) calcd.
+
for C H N O S [M+H] : 415.1184; found 415.1216.
2
3
18
4
2
4.1.2.9 2-(4-((1-(2,4-Difluorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]
thiazole (5i)
o
-1
Yield: 93 %, M.P.: 158-161 C; White Solid; IR (KBr) ν cm : 3084 (Aromatic C-H
1
stretching), 1603 (C=C stretching), 1466 (N-N stretching), 1445 (N=N stretching); H NMR
(300 MHz, CDCl )  ppm = 5.31 (s, 2H, OCH ), 7.01-8.08 (m, 12H, merged signals, Ar-H
3
2
and triazolyl-H); 13C NMR (125 MHz, CDCl )  ppm = 61.96, 115.11, 118.49, 120.79,
3
1
1
20.86, 121.49, 122.83, 124.65, 126.20, 127.09, 128.97, 129.17, 130.83, 134.81, 135.60,
+
37.66, 144.69, 154.10, 157.32, 160.24, 167.51; LCMS (ESI) calcd. for C H F N OS
2
2
15
2
4
+
[M+H] : 421.09 and found 421.09.
4.1.2.10 2-(4-((1-Mesityl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole (5j)
o
1
Yield: 89 %, M.P.: 145-147 C; White solid; H NMR (300 MHz, CDCl )  ppm = 1.94 (s,
3
6
H, 2xCH ), 2.33 (s, 3H, CH ), 5.39 (s, 2H, CH ), 6.91- 8.06 (m, 11H, merged signals, Ar-H
3 3 2
13
and triazolyl-H); C NMR (100 MHz, CDCl )  ppm = 16.80, 20.41, 61.21, 115.50, 122.00,
3

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22.30, 124.27, 124.97, 125.71, 126.35, 128.12, 128.66, 133.07, 134.06, 134.25, 139.40,
DOI: 10.1039/C9NJ00377K
+
+
142.18, 153.45, 160.31, 166.80; HRMS (ESI) calcd. for C H N OS [M+H] : 427.1548 and
2
5
23
4
found 427.1582.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
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4
4
4
4
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5
5
5
5
5
5
5
5
6
0
1
2
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4
5
6
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0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
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7
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0
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.1.2.11 2-(4-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]thiazole (5k)
o
1
Yield: 94 %, M.P.: 199-201 C; White solid; H NMR (300 MHz, CDCl )  ppm = 5.27 (s,
3
2
H, OCH ), 5.33 (s, 2H, N-CH ), 7.06-8.06 (m, 14H, merged signals, Ar-H and triazolyl-H);
2 2
1
3
C NMR (100 MHz, CDCl )  ppm = 52.22, 61.29, 115.48, 119.20, 122.17,122.47, 123.75,
3
1
25.10, 125.80, 126.48, 128.85, 128.88, 134.24, 138.37, 142.05, 153.65, 160.55, 164.12,
+
+
166.96; HRMS (ESI) calcd. for C H N OS [M+H] : 399.1235 and found 399.1281.
2
3
19
4
4
.1.2.12 2-(4-((1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl) benzo[d]
thiazole (5l)
Yield: 95 %, M.P.: 161-164 C; White solid; H NMR (300 MHz, CDCl )  ppm = 5.25 (s,
o
1
3
2
H, OCH ), 5.50 (s, 2H, N-CH ), 7.01-8.03 (m, 13H, merged signals, Ar-H and triazolyl-H);
2 2
1
3
C NMR (125 MHz, CDCl )  ppm = 53.75, 62.37, 115.40, 116.30, 116.52, 121.74, 122.78,
3
1
1
4
23.09, 125.09, 126.45, 127.25, 129.36, 130.19, 130.27, 130.44, 135.09, 154.41, 160.63,
+
+
64.36, 167.82; HRMS (ESI) calcd. for C H FN OS [M+H] : 417.1141 and found
2
3
18
4
17.1200.
4.1.2.13 2-(4-((1-(2-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]
thiazole (5m)
o
1
Yield: 89 %, M.P.: 144-146 C; White solid; H NMR (300 MHz, CDCl )  ppm = 5.28 (s,
3
2
H, OCH ), 5.69 (s, 2H, N-CH ), 7.06-8.06 (m, 13H, merged signals, Ar-H and triazolyl-H);
2 2
1
3
C NMR (125 MHz, CDCl )  ppm = 51.29, 62.29, 115.37, 121.68, 123.01, 123.37, 125.02,
3
1
26.38, 127.12, 127.79, 129.29, 130.12, 132.39, 133.69, 135.03, 154.34, 160.61, 167.79;
+
+
HRMS (ESI) calcd. for C H ClN OS [M+H] : 433.0812 and found 433.0893.
2
3
18
4
4.1.2.14 2-(4-((1-(3-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl) benzo[d]
thiazole (5n)
o
1
Yield: 88 %, M.P.: 158-161 C; White solid; H NMR (300 MHz, CDCl )  ppm = 5.26 (s,
3
2
H, OCH ), 5.69 (s, 2H, N-CH ), 7.07-8.06 (m, 13H, merged signals, Ar-H and triazolyl-H);
2 2
1
3
C NMR (125 MHz, CDCl )  ppm = 51.74, 62.36, 115.42, 121.72, 123.07, 123.34, 125.06,
3

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DOI: 10.1039/C9NJ00377K
+
+
160.65, 167.84; HRMS (ESI) calcd. for C H ClN OS [M+H] : 433.0812 and found
2
3
18
4
4
33.0893.
0
1
2
3
4
5
6
7
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9
0
1
2
3
4
5
6
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8
9
0
1
2
3
4
5
6
7
8
9
0
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0
4
.1.2.15 2-(4-((1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzo[d]
thiazole (5o)
Yield: 87 %, M.P.: 191-194 C; White solid; H NMR (300 MHz, CDCl )  ppm = 5.26 (s,
o
1
3
2
H, OCH ), 5.48 (s, 2H, N-CH ), 7.04-8.03 (m, 13H, merged signals, Ar-H and triazolyl-H);
2 2
13
C NMR (125 MHz, CDCl )  ppm = 53.82, 62.37,115.43, 121.75, 122.86,123.11, 123.30,
3
125.10, 126.46, 127.27, 129.38, 129.93, 132.59, 133.60, 135.10, 154.41, 160.61, 167.82;
+
+
HRMS (ESI) calcd. for C H BrN OS [M+H] : 477.0340 and found 477.0390.
23 18
4
4
.1.2.16 2-(4-((4-(Benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-phenyl
acetamide (5p)
Yield: 94 %, M.P.: 233-235 C; White solid; H NMR (300 MHz, DMSO-d )  ppm = 5.31
o
1
6
(
s, 2H, CH ), 5.38 (s, 2H, OCH ), 7.09-8.31 (m, 14H, merged signals, Ar-H and triazolyl-H),
2 2
13
1
1
1
4
0.48 (s, 1H, amido-NH); C NMR (125 MHz, DMSO-d )  ppm = 52.22, 61.29, 115.48,
6
19.20, 122.17, 122.47, 123.75, 125.10, 125.80, 126.48, 128.85, 128.88, 134.24, 138.37,
+
+
42.05, 153.65, 160.55, 164.12, 166.96; HRMS (ESI) calcd. for C H N O S [M+H] :
24 20
5
2
42.1293 and found 442.1340.
4.1.2.17 2-(4-((4-(Benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(3-
chlorophenyl)acetamide (5q)
o
1
Yield: 88 %, M.P.: 209-211 C; White solid; H NMR (300 MHz, DMSO-d )  ppm = 5.34
6
(
s, 2H, CH ), 5.43 (s, 2H, OCH ), 7.17-8.35 (m, 13H, merged signals, Ar-H and triazolyl-H),
2 2
1
3
1
0.74 (s, 1H, amido-NH); C NMR (125 MHz, DMSO-d )  ppm = 52.60, 61.66, 115.89,
6
118.02,119.11, 122.61, 122.89, 123.92, 125.53, 126.19, 126.91, 129.26, 131.06, 133.58,
+
1
34.64, 140.19, 142.48, 154.06, 160.96, 165.04, 167.37; HRMS (ESI) calcd. for
+
C H ClN O S [M+H] : 476.0903 and found 476.0938.
2
4
19
5
2
4
.1.2.18 2-(4-((4-(Benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(4-
chlorophenyl)acetamide (5r)

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o
1
Yield: 92 %, M.P.: 220-222 C; White solid; H NMR (300 MHz, DMSO-d )  ppm = 5.31
6
(
s, 2H, CH ), 5.38 (s, 2H, OCH ), 7.24-8.32 (m, 13H, merged signals, Ar-H and triazolyl-H),
2
2
1
3
10.65 (s, 1H, amido-NH); C NMR (125 MHz, DMSO-d )  ppm = 52.72, 61.78, 116.01,
6
1
1
21.28, 122.74, 123.04, 126.31, 126.44, 127.04, 127.67, 127.67, 129.37, 132.09, 134.77,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
37.86, 142.60, 154.17, 161.07, 164.89, 167.50; HRMS (ESI) calcd. for C H ClN O S
2
4
19
5
2
+
[
M+H] : 476.0903 and found 476.0935.
4
.1.2.19 2-(4-((4-(Benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(m-
tolyl)acetamide (5s)
o
1
Yield: 87 %, M.P.: 204-206 C; White solid; H NMR (300 MHz, DMSO-d )  ppm = 2.30
6
(s, 3H, CH ), 5.33 (s, 2H, CH ), 5.38 (s, 2H, OCH ) 6.91-8.38 (m, 13H, merged signals, Ar-H
3
2
2
1
3
and triazolyl-H), 10.46 (s, 1H, amido-NH); C NMR (100 MHz, DMSO-d )  ppm = 21.89,
6
5
1
2.76, 61.80, 116.03, 116.91, 120.27, 122.76, 123.04, 125.01, 125.68, 126.32, 127.06,
29.49, 129.41, 134.78, 136.67, 136.85, 138.30, 142.56, 154.19, 161.10, 164.62, 167.52;
+
+
HRMS (ESI) calcd. for C H N O S [M+H] : 456.1450 and found 456.1481.
2
5
22
5
2
4
.1.2.20
tolyl)acetamide (5t)
Yield: 92 %, M.P.: 240-243 C; White solid; H NMR (300 MHz, DMSO-d )  ppm = 2.28
2-(4-((4-(Benzo[d]thiazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(p-
o
1
6
(
s, 3H, CH ), 5.33 (s, 2H, CH ), 5.37 (s, 2H, OCH ), 7.14-8.34 (m, 13H, merged signals, Ar-
3 2 2
1
3
H and triazolyl-H), 10.45 (s, 1H, amido-NH); C NMR (125 MHz, DMSO-d )  ppm =
6
2
0.80, 52.55, 61.62, 115.85, 119.55, 122.58, 122.86, 125.50, 126.14, 126.88, 129.23, 129.65,
+
133.10, 134.61, 136.24, 138.87, 142.38, 154.01, 160.92, 164.25, 167.34; HRMS (ESI) calcd.
+
for C H N O S [M+H] : 456.1450 and found 456.1482.
2
5
22
5
2
4
.2. Biological
4.2.1 Cell culture growth conditions
The breast cancer cells MCF-7 procured from cell repository, NCCS, Pune (India).
The MCF-7 cells were maintained in Glutamax DMEM, (Life technologies Inc. USA);
containing 10% v/v heat-inactivated FBS (Life technologies Inc. USA) and 0.01 mg/mL
o
Insulin. The cells when achieved 70%-85% confluence at 37 C and 5% CO incubator were
2
passaged in a sub cultivation ratio 1:3 to 1:5. The confluent cells were trypsinised with 1X

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Trypsin-EDTA solution (Life technologies Inc. USA), counted and aliquoted at the desired
density for growth assays.
4
.2.2 Determinations of IC50
0
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2
3
4
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7
8
9
0
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2
3
4
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A serial dilution of newly synthesized compounds (5a-t) was prepared in DMSO. The
compounds were added into the 24 h grown MCF-7 cells in RPMI 1640 with FBS (10 % v/v).
3
The seeding density for cell line were >5×10 cell per well/200 mL of medium. The cell lines
were incubated for 24 h. The IC50 was determined by using EIA scan at 490 nm. The
inhibitory concentration (Ic ) was determined by addition of the compound in 24 h grown
5
0
cells. It explains the MIC of compounds determined by using the MTT formation of
compounds.
4.2.3 CellTiter 96 aqueous one solution cell proliferation assay
Assays are performed by adding a small amount of MTT reagent directly to culture
wells, incubating for 2h and recording absorbance at 490 nm with a 96-well plate reader. The
quantity of formazan product was measured at 490 nm absorbance which directly
proportional to the number of living cells in culture. The cells were exposed to compounds at
secondary density >5000 cell /100 mL /well in 24 well plates. 20 μL of MTT Reagent was
added into each well of the 96-well assay plate containing the cells with compounds in 100
o
μL of culture medium. The plate incubated at 37 C for 2 h in a humidified, 5 % (w/v) CO
2
atmosphere. The absorbance recorded at 490 nm using a 96-well plate reader.
4
.2.4 Antimicrobial activity determination
To determine the antimicrobial activities of each compound, the disk diffusion
6
4
method was utilized. Using cultures of E. coli strains; bacterial species were cultured on
nutrient agar media. Inoculums suspension (100 CFU per microliter) was prepared from
microorganism in broth media, nutrient broth inoculated with bacterial species was incubated
o
for 24 h at 37 C. After incubation, the culture tubes were exposed to the compounds at
different concentrations zero to 50 microgram/mL. The optical density was observed at 540
nm after 24 h. The dose dependent growth was analysed by using GraphPad Prism 7.
Conflict of Interest
The authors declare no conflict of interest.

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Acknowledgments
Authors are thankful to Professor D. B. Ingle for his invaluable discussions and guidance.
Authors acknowledge to CDRI, Lucknow for providing spectral facilities. Authors are also
grateful to Deogiri College, Aurangabad for antibacterial and anticancer evaluation and one
of the authors STD is grateful to U.G.C., New Delhi, India for financial assistance in the form
of NET Senior Research Fellowship.
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References
[
1] B. S. Holla, M. Mahalinga, M. S. Karthikeyen, B. Poojary, P. M. Akberali and N. S.
Kumari, Eur. J. Med. Chem., 2005, 40, 1173-1178.
[
2] K. B. Sharpless and R. Manetsch, Expert Opin. Drug Discovery., 2006, 1, 525-538.
3] D. Fournier, R. Hoogenboom and U. S. Schubert, Chem. Soc. Rev., 2007, 36, 1369-1380.
[
[4] A. B. Braunschweig, W. R. Dichtel, O. S. Miljanic, M. A. Olson, J. M. Spruell, S. I.
Khan, J. R. Heath and J. F. Stoddart, Chem. Asian J., 2007, 2, 634-647.
[
5] K. V. Vani, G. Ramesh and C. V. Rao, J. Heterocycl. Chem., 2016, 53, 719-726.
6] S. G. Agalave, S. R. Maujan and V. S. Pore, Chem. Asian J., 2011, 6, 2696-2718.
[
[7] D. Dheer, V. Singh and R. Shankar, Bioorg. Chem., 2017, 71, 30-54.
[
8] K. Shalini, N. Kumar, S. Drabu and P. K. Sharma, Beilstein J. Org. Chem., 2011, 7, 668-
77.
9] W. S. Horne, M. K. Yadav, C. D. Stout and M. R. Ghadiri, J. Am. Chem. Soc., 2004, 126,
5366-15367.
6
[
1
[10] M. Ashok and B. S. Holla, J. Pharmacol. Toxicol., 2007, 2, 256-263.
[
11] M. H. Shaikh, D. D. Subhedar, B. B. Shingate, F. A. K. Khan, J. N. Sangshetti, V. M.
Khedkar, L. Nawale, D. Sarkar, G. R. Navale and S. S. Shinde, Med. Chem. Res., 2016,
2
5, 790-804.
[
12] M. S. Costa, N. Boechat, E. A. Rangel, F. C. Silva, A. M. T. de Souza, C. R. Rodrigues,
H. C. Castro, I. N. Junior, M. C. S. Lourenco, S. M. S. V. Wardell and V. F. Ferreira,
Bioorg. Med. Chem., 2006, 14, 8644-8853.
[
13] G. Wang, Z. Peng. J. Wang, J. Li and X. Li, Bioorg. Med. Chem. Lett., 2016, 26, 5719-
5
723.
[14] R. Bollu, J. D. Palem, R. Bantu, V. Guguloth, L. Nagarapu, S. Polepalli and N. Jain,
Eur. J. Med. Chem., 2015, 89, 138-146.

New Journal of Chemistry
Page 24 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
View Article Online
[
15] H. B. Lazrek, M. Taourirte, T. Oulih, J. L. Barascut, J. L. Imbach, C. Pannecouque, M.
DOI: 10.1039/C9NJ00377K
Witrouw and E. De Clercq, Nucleosides Nucleotides Nucleic Acids., 2001, 12, 1949-
960.
1
[
16] E. C. Costa, T. B. Cassamale, D. B.Carvalho, N. S. Cassemiro, C. C. Tomazela, M. C. S.
Marques, M. Ojeda, M. F. C. Matos, S. Albuquerque, A. C. M. Baroni and C. C. P.
Arruda, J. Braz. Chem. Soc., 2016, 21, 802-812.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
[
17] A. Krajczyk, K. Kulinska, T. Kulinski, B. L. Hurst, C. W. Day, D. F. Smee, T.
Ostrowski, P. Januszczyk and J. Zeidler, Antivir. Chem. Chemother., 2014, 23, 161-171.
18] Y. Yang, B. A. Rasmussen and D. M. Shlaes, Pharmacol. Ther., 1999, 83, 141-151.
[
[19] N. G. Aher, V. S. Pore, N. N. Mishra, A. Kumar, P. K. Shukla, A. Sharma and M. K.
Bhat, Bioorg. Med. Chem. Lett., 2009, 19, 759-763.
[
[
[
[
20] T. M. Dhamelia, R. Tiwari, A. Banerjee, S. Pancholia, D. Sriram, D. Panda and A. K.
Chakraborti, Eur. J. Med. Chem., 2018, 155, 364-380.
21] R. S. Keri, M. R. Patil,; S. A. Patil and S. Budagumpi, Eur. J. Med. Chem., 2015, 89,
2
07-251.
22] M. Singh, S. K. Singh, M. Gangwar, G. Nath and S. K. Singh, RSC Adv., 2014, 4,
19013-19023.
23] M. Chhabra, S. Sinha, S. Banerjee and P. Paira, Bioorg. Med. Chem. Lett., 2016, 26,
2
13-217.
[
24] Y. Cho, T. R. Ioerger and J. C. Sacchettini, J. Med. Chem., 2008, 51, 5984-5992.
25] N. H. Cano, M. S. Ballari, A. G. Lopez and A. N. Santiago, J. Agric. Food Chem., 2015,
[
6
3, 3681-3686.
[
[
[
26] S. R. Pattan, C. Suresh, V. D. Pujar, V. V. K. Reddy, V. P. Rasal and B. C. Koti, Ind. J.
Chem., 2005, 44, 2404-2408.
27] C. Kharbanda, M. Salam, H. Hamid, K. Javed, S. Bano, A. Dhulap, Y. Ali, S . Nazreen
and S. Haider, Bioorg. Med. Chem., 2014, 22, 5804-5812.
28] T. Akhtar, S. Hameed, N. Al-Masoudi, R. Loddo, P. Colla, Acta Pharm., 2008, 58, 135-
149.
[29] S. J. Schnitt, Mod Pathol., 2010, 23, 60-64.
[
30] N. S. Goldstein and C. R. Ziegfeld, Early Diagn Treat Cancer Ser:Breast Cancer., 2011
55-69.
[
31] P. W. Mantyh, D. R. Clohisy, M. Koltzenburg and S. P. Hunt, Nat Rev. Cancer., 2002,
2
, 201-209.

Page 25 of 27
New Journal of Chemistry
1
2
3
4
5
6
7
8
9
View Article Online
DOI: 10.1039/C9NJ00377K
[
[
[
[
[
32] A. Ghafoor A. Jemal, E. Ward, V. Cokkinides, R. Smith and M. Thun. CA Cancer J
Clin., 2003, 53, 342-355
33] R. M. Kumbhare, U. B. Kosurkar, M. J. Ramaiah, T. L. Dadmal, S. N. C. V. L.
Pushpavalli and M. Pal-Bhadra, Bioorg. Med. Chem. Lett,. 2012, 22, 5424-5427.
34] M. K. Singh, R. Tilak, G. Nath, S. K. Awasthi and A. Agarwal, J. Med. Chem., 2013,
63, 635-644.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
35] F. Mir, S. Shafi, M. S. Zaman, N. P. Kalia, V. S. Rajput, C. Mulakayala, N. Mulakayala,
I. A. Khan and M. S. Alam, Eur. J. Med. Chem., 2014, 76, 274-283.
36] N. Rezki, Molecules., 2016, 21, 505-517.
[37] R, Huisgen, Angew. Chem. Int. Ed. Engl., 1963, 2, 565-598.
38] H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem. Int. Ed., 2001, 40, 2004-
021.
[39] C. W. Tornoe, C. Christensen and M. Meldal, J. Org. Chem., 2002, 67, 3057-3064.
[
2
[
40] T. G. Kraljevic, A. Harej, M. Sedic, S. K. Pavelic, V. Stepanic, D. Drenjancevic, J.
Talapko and S. Raic-Malica, Eur. J. Med. Chem., 2016, 124, 794-808.
[
41] F. Alonso, Y. Moglie, G. Radivoy and M. Yus, J. Org. Chem., 2011, 76, 8394-8405.
[42] A. Kaur, S. Mann, B. Goyal, B. Pal and D. Goyal, RSC Adv., 2016, 6, 102733-102743.
[
[
[
43] H. Naeimi, R. Shabbani and M. Moradien, Appl. Organometal. Chem. 2017, 31, 3626-
3
632.
44] P. V. Chavan, K. S. Pandit, U. V. Desai, M. V. Kulkarni and P. P. Wadgaonkar, RSC
Adv., 2014, 4, 42137-42146.
45] F. Nador, M. A. Volpe, F. Alonso, A. Feldhoff, A. Kirschning and G. Radivoy, Appl.
Catal. A., 2013, 455, 39-45.
[46] H. Sharghi, R. Khalifeh and M. M. Doroodmand, Adv. Synth. Catal., 2010, 352, 3208-
214.
3
[
47] B. S. P. Kumar, K. H. P. Reddy, B. Madhav, K. Ramesh and Y. V. D. Nageswar,
Tetrahedron Lett., 2012, 53, 4595-4599.
[48] M. J. Gruselle, Organomettalic Chem., 2015, 793, 93-101.
[
49] J. M. Hughes and J. Rakovan, Rev. Mineral. Geochem., 2002, 48, 1-12.
50] B. M. Choudary, C. Sridhar, M. L. Kantam, G. T. Venkanna and B. Sreedhar, J. Am.
Chem. Soc. 2005, 127, 9948-9949.
[
[
51] S. R. Mulla, S. S. Chavan, S. M. Inamdar, M. Y. Pathan and T. M. Y. Shaikh,
Tetrahedron lett., 2012, 53, 1826-1829.

New Journal of Chemistry
Page 26 of 27
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
View Article Online
DOI: 10.1039/C9NJ00377K
[
[
[
52] M. L. Kantam, G. T. Venkanna, C. Sridhar and K. B. Shivakumar, Tetrahedron lett.,
2006, 47, 3897-3899.
53] S. R. Mulla, S. M. Inamdar, M. Y. Pathan, T. Y. Shaikh and S. S. Chavan, RSC Adv.,
2
012, 2, 12818-12823.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
54] S. Shanmugam and B. Gopal, Ceramics Inter., 2014, 40, 15655-15662.
[55] Y. Masuyama, K. Yoshikawa, N. Suzuki K. Hara and A. Fukuoka, Tetrahedron lett.,
011, 52, 6916-6918.
2
[
56] S. A. R. Mulla, S. S. Chavan, M. Y. Pathan, S. M. Inamdar and T. M. Y. Shaikh, RSC
Adv., 2015, 5, 24675-24680.
[57] M. L. Kantam, G. T. Venkanna, C. Sridhar, B. Sreedhar and B. M. Choudary, J. Org.
Chem., 2006, 71, 9522-9524.
[
[
[
[
[
[
58] M. T. Gabr, N. S. El-Gohary, E. R. El-Bendary, M. M. El-Kerdawy, EXCLI J., 2014, 13,
573-585.
59]C.A. Lipinski, L. Lombardo, B.W. Dominy and P. Feeney, J. Adv. Drug Deliv. Rev.,
2
001, 46, 3-26.
60] Molinspiration Chemoinformatics Brastislava, Slovak Republic, Available from:
http://www.molinspiration.com/cgi-bin/properties 2014.
61] Y. H. Zhao, M. H. Abraham, J. Le, A. Hersay, C. N. Luscombe, G. Beck, B. Sherbone
and I. Cooper, J. Pharm. Res., 2002, 19, 1446-1457.
62] Drug-likeness
and
molecular
property
prediction,
available
from:
http://www.molsoft.com/mprop.
63] K. C. Tiew, D. Dou, T. Teramoto, H. Lai, K. R. Alliston, G. H. Lushington, R.
Padmanabhan and W. C. Groutas, Bioorg. Med. Chem., 2012, 20, 1213-1221.
[64] M. Balouiri, M. Sadiki and S. K. Ibnsouda, J. Pharma. Anal., 2016, 6, 71-79.

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New Journal of Chemistry
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View Article Online
DOI: 10.1039/C9NJ00377K
A Table of Contents Entry
Copper Fluorapatite assisted synthesis of new 1,2,3-triazoles bearing
benzothiazolyl moiety and their antibacterial and anticancer activities
a
a
b
a
Sambhaji T. Dhumal, Amarsinh R. Deshmukh, Kiran R. Kharat, Bhaskar R. Sathe,
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Santosh S. Chavan, Ramrao A. Mane
aDepartment of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad,
31004, India.
4
bCentre for Advanced Life Sciences, Deogiri College, Aurangabad- 431005, India.
cChemistry and Chemical Bioengineering Unit, Okinawa Institute of Science and Technology
Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0495 (Japan).
*Corresponding Author: manera2011@gmail.com
N3
Anticancer
CuFAP
CuFAP
S
N
R
O
N
N
N
N3
R
O
S
N
N
R
O
N
N
O
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N3
HN
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S
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O
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CuFAP
O
NH
Antibacterial
R
New 1,2,3-triazoles with benzothiazolyl scaffold have been first time synthesized using
Copper Fluorapatite as a catalyst and their antibacterial and anticancer activities are reported.