Synthesis and antibacterial activity of chalcone derivatives containing thioether triazole

Article abstract of DOI:10.1002/jhet.3755

The infection of Xanthomonas oryzae pv. Oryzae (Xoo), Ralstonia solanacearum (Rs), and Xanthomonas axonopodis pv. Citri (Xac) has become a major problem in agricultural production. In this study, a series of novel chalcone derivatives containing thioether triazoles were designed and synthesized. The structures of the novel compounds were systematically characterized via ¹H-NMR, ¹³C-NMR, and HRMS. Moreover, the antibacterial activity results showed that E₁₀, E₁₁, E₁₅, and E₁₆ have adequate antibacterial activities against Xoo, Rs, and Xac. Among the different compounds, E₁₅ exhibited remarkable inhibitory effect against Xac with an EC₅₀ of 9.1 μg.mL^-1, which was better than that of commercial agent bismerthiazol (54.9 μg.mL^-1). In addition, the possible antibacterial mechanism of the target compound E₁₅ against Xac was studied via scanning electron microscopy (SEM).

Full text of DOI:10.1002/jhet.3755

Received: 22 April 2019
DOI: 10.1002/jhet.3755
Revised: 7 September 2019
Accepted: 10 September 2019
A R T I C L E
Synthesis and antibacterial activity of chalcone derivatives
containing thioether triazole
Ying Chen1 | Pu Li1 | Mei Chen1 | Jun He1 | Shijun Su1 | Ming He1 | Hua Wang2 |
Wei Xue1
1 State Key Laboratory Breeding Base of
Abstract
Green Pesticide and Agricultural
The infection of Xanthomonas oryzae pv. Oryzae (Xoo), Ralstonia solanacearum
(Rs), and Xanthomonas axonopodis pv. Citri (Xac) has become a major problem
in agricultural production. In this study, a series of novel chalcone derivatives
containing thioether triazoles were designed and synthesized. The structures of
the novel compounds were systematically characterized via 1H‐NMR, 13C‐
NMR, and HRMS. Moreover, the antibacterial activity results showed that
E10, E11, E15, and E16 have adequate antibacterial activities against Xoo, Rs,
and Xac. Among the different compounds, E15 exhibited remarkable inhibitory
effect against Xac with an EC50 of 9.1 μg.mL‐1, which was better than that of
commercial agent bismerthiazol (54.9 μg.mL‐1). In addition, the possible anti-
bacterial mechanism of the target compound E15 against Xac was studied via
scanning electron microscopy (SEM).
Bioengineering, Center for Research and
Development of Fine Chemicals, Guizhou
University, Guiyang 550025, China
2 Institute for Plant Protection and Soil
Science, Hubei Academy of Agricultural
Sciences, Wuhan 430064, China
Correspondence
Hua Wang, Institute for Plant Protection
and Soil Science, Hubei Academy of
Agricultural Sciences, Wuhan, 430064,
China.
Email: wanghua4@163.com
Wei Xue, State Key Laboratory Breeding
Base of Green Pesticide and Agricultural
Bioengineering, Center for Research and
Development of Fine Chemicals, Guizhou
University, Guiyang, 550025, China.
Email: wxue@gzu.edu.cn
Funding information
National Nature Science Foundation of
China, Grant/Award Number: 21462012;
National Key Research and Development
Program of China, Grant/Award Number:
2017YFD0200506
1 | INTRODUCTION
sustainable development.[2,3] In this direction, much
research effort has been focused on the development of
In recent years, the infection of crops by microbial diseases,
especially Xanthomonas oryzae pv. Oryzae (Xoo), Ralstonia
solanacearum (Rs), and Xanthomonas axonopodis pv. Citri
(Xac), has seriously affected the quantity and quality of
products, with serious consequences to human health.[1]
Therefore, the effective prevention and control of plant
microbial diseases is critical for promoting agricultural
new varieties of pesticides.[4,5]
As important natural products, flavonoids, and
isoflavones exist in edible plants.[6] Chalcone belongs
to the core skeleton unit of isoflavones and flavonoids,
having a broad‐spectrum of biological activities such as
anti‐inflammatory,[7,8] antibacterial,[9–11] antiprolifera-
tive,[12] insecticidal,[13] antioxidant,[14] antiviral,[15,16]
antifungal,[17] and anticancer.[18] Chu et al. reported a
series of chalcone derivatives with cationic antimicrobial
Ying Chen and Pu Li contributed equally to this work.
J Heterocyclic Chem. 2020;1–8.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals, Inc.
1

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CHEN ET AL.
peptides, and showed that the resistant bacteria MRSA,
KPC, and NDM have good bactericidal activities.[19] El‐
Hashash and coworkers synthesized three new chalcone
2 | RESULTS AND DISCUSSION
2.1 | Chemistry
derivatives
containing
aminoguanidine
or
acylhydrazone, which showed good antimicrobial activi-
ties.[20] Reddy et al. designed and synthesized a series of
β‐carboline derivatives containing chalcone structures.
Bioactivity analysis indicated that the compounds have
good inhibitory effects on the tested bacteria.[21] Several
studies have shown that triazole derivatives have biolog-
ical activities such as anti‐inflammatory,[22] antibacte-
rial,[23,24] antifungal,[25] antiviral,[26] anticancer,[27] and
antituberculosis.[28] For example, Singh et al. developed
a series of substituted aryl azide compounds containing
o‐phenylenediamines, which exhibited antifungal
activities.[29] Struga reported the synthesis of twenty‐
one thiourea‐containing derivatives by reacting 3‐
amino‐1H‐1,2,4‐triazole with an aromatic isothiocyanate
and aliphatic, and these compounds exhibited antibacte-
rial activities.[30]
Although chalcone and thioether triazole containing
compounds have good biological activities, the antibacte-
rial activities of chalcone compounds containing
thioether triazole heterocycles have not been reported.
Based on the advantages of chalcone and thioether tri-
azole containing compounds, a series of novel chalcone
derivatives containing thioether triazole were synthe-
sized in the present work. Meanwhile, the antibacterial
activity of the target compounds was investigated by tur-
bidity method. (Scheme 1)
The chalcone compounds containing thioether triazole
was successfully synthesized, as showed in Scheme 1. In
a typical procedure, intermediates A and B were
synthesized using hydrazine hydrate, carbon disulfide,
and glacial acetic acid as raw materials.[31] The hydroxy‐
substituted acetophenone reacted with substituted form-
aldehyde to give the intermediate C. The intermediate D
was obtained from the reaction between intermediate C
and 1,2‐dibromoethane.[32–35] Finally, intermediates B
and D were stirred at room temperature for 8 h in DMF
to give the target compounds E. The 1H‐NMR, 13C‐
NMR, and HRMS of all the compounds were consistent
with their structures. The characteristic peak of the target
compounds at 5.86‐5.89 ppm belong to –NH2. –CH2–
group of the compounds exhibits three peaks at 4.32‐
4.38 ppm and 3.48‐3.53 ppm. The HRMS spectrum of
compounds, HRMS [M+H]+ indicates that the target
products have stable structure.
2.2 | Bioactivities
The in vitro antibacterial activities of the target com-
pounds against Xoo, Rs, and Xac were determined
through the turbidity method. The results are shown in
Tables 1, 2, and 3 by comparison with the data of
SCHEME 1 The synthetic route of the
target compounds.

CHEN ET AL.
3
TABLE 1 Inhibition (%) effect of title compounds against Xoo, Rs, and Xac
XOO (%)
Rs (%)
Xac (%)
Compounds
X
R
100 μg/mL
50μg/mL
100 μg/mL
50μg/mL
100 μg/mL
50μg/mL
E1
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
2‐O
4‐O
4‐O
4‐O
‐
Thiophen‐2‐yl
4‐F‐Ph
45.1 0.5
48.3 2.7
51.8 7.8
42.8 0.4
64.1 0.5
42.7 0.1
36.0 0.8
22.0 0.4
56.0 3.2
85.9 0.1
56.5 5.9
41.1 1.4
32.9 2.9
56.3 0.7
54.5 0.3
42.1 2.9
47.0 3.0
34.6 0.9
38.0 0.3
12.8 0.9
34.1 0.9
54.9 2.9
31.3 0.4
21.1 0.4
11.4 0.5
45.9 1.6
76.4 1.2
51.4 1.1
22.3 0.5
11.6 0.9
43.6 0.6
47.6 1.4
32.0 0.8
39.6 6.0
39.9 0. 8
69.5 6.2
46.9 0.7
64.0 2.3
65.6 1.5
42.3 1.1
34.8 0.8
54.0 3.1
43.0 4.7
62.7 2.6
66.9 1.2
63.9 0.9
47.1 2.6
60.6 3.9
42.8 3.4
41.5 0.9
61.1 6.1
13.1 0.7
48.3 0.3
17.9 1.7
59.3 7.1
51. 7 0.7
37.9 0.4
29.1 0.1
43.9 2.5
24.2 1.9
54.5 5.7
37.2 5.3
47.0 1.7
24.3 1.7
33.6 5.7
28.2 4.0
37.3 3.2
49.5 5.2
42.6 2.6
70.7 4.2
68.0 2.3
50.8 1.9
40.1 0.7
50.2 3.3
46.1 2.5
57.3 0.7
47.9 2.1
50.3 0.8
77.1 0.8
48.7 4.5
46.0 7.7
71.3 2.8
84.1 6.6
76.8 3.8
59.5 7.6
34.1 2.0
63.3 1.6
53.2 2.7
42.0 2.4
34.6 1.6
40.8 0.7
38.6 2.5
44.1 2.3
36.6 3.5
45.6 2.9
66.0 1.6
36.3 4.9
32.4 8.3
68.1 1.2
72.9 2.8
62.7 2.3
49.4 5.7
E2
E3
2,4‐di‐OCH3‐Ph
3‐NO2‐Ph
E4
E5
2‐OCH3‐Ph
4‐OCH3‐Ph
4‐Methylthiazol‐5‐yl
Furan‐2‐yl
3,4‐di‐OCH3‐Ph
4‐Br‐Ph
E6
E7
E8
E9
E10
E11
2,4‐di‐Cl‐Ph
3‐Br‐Ph
E12
E13
3‐CF3‐Ph
E14
Thiophen‐2‐yl
4‐Cl‐Ph
E15
E16
2‐Cl‐Ph
Bismerthiazol
‐
commercially available antibacterial agent bismerthiazol
(20% wettable powder).
Xac, at a concentration of 100 μg.mL‐1, the inhibition
rates of compounds E11, E14, E15, and E16 on Xac were
77.1, 71.3, 84.1, and 76.8%, respectively, which were bet-
ter than commercial agent bismerthiazol (59.5%). When
the concentration was 50 μg.mL‐1, the inhibition rates of
compounds E2, E11, E14, and E15 on Xac were 63.3, 66.0,
68.1, and 72.9%, respectively, which were better again
than commercial agent bismerthiazol (49.4%).
The antibacterial activity test results of the target com-
pounds E1–E16 (Table 1) showed that all the compounds
exhibited certain inhibitory activities against Xoo, Rs,
and Xac. Regarding the antibacterial activity against
Xoo, at a concentration of 100 μg.mL‐1, the inhibition
rates of compounds E5, E10, E11, and E14 were 64.1,
85.9, 56.5, and 56.3%, respectively, which were better
than commercial agent bismerthiazol (47.0%). When the
concentration was 50 μg.mL‐1, the inhibition rates of
compounds E5, E10, E11, and E15 against Xoo were 54.9,
76.4, 51.4, and 47.6%, respectively, which were better
again than commercial agent bismerthiazol (39.6%). For
Rs, at a concentration of 100 μg.mL‐1, the inhibition rates
of compounds E2, E4, E5, and E11 were 69.5, 64.0, 65.6,
and 66.9%, respectively, as compared to 61.1% of commer-
cial agent bismerthiazol. When the concentration was 50
μg.mL‐1, the inhibition rates of compounds E4, E5, and
E10 were 59.3, 51.7, and 54.5%, respectively, better than
that of commercial agent bismerthiazol (49.5%). For
The commercial bismerthiazol was used as the control
agent, and the compound E10 was selected for the deter-
mination of Xoo EC50 value (Table 2). The results shown
that the EC50 value of the compound E10 was 10.8 μg.mL‐
1
,
which were better than commercial agent
bismerthiazol (69.3 μg.mL‐1).
Table 3 shows that the Xac EC50 values of the target
compounds are better than the control drug. The EC50
values of compounds E11, E15, and E16 are 15.1, 9.1, and
17.5 μg.mL‐1, respectively, which were better than com-
mercial agent bismerthiazol (54.9 μg.mL‐1).
In general, when the substituent R=4‐Br‐Ph, the tar-
get compound exhibits a good inhibitory activity against
TABLE 2 EC50 values of several target compounds against Xoo
Compounds
X
R
Toxic regression equation
r
EC50/(μg/mL)
E10
2‐O
4‐Br‐Ph
y = 1.0637x + 3.9028
y = 2.8364x + 0.5935
0.9833
0.9897
10.8 1.1
69.3 2.0
Bismerthiazol
‐
‐

4
CHEN ET AL.
TABLE 3 EC50 values of several target compounds against Xac
Compounds
X
R
Toxic regression equation
r
EC50/(μg/mL)
E2
2‐O
2‐O
2‐O
4‐O
4‐O
4‐O
‐
4‐F‐Ph
y = 0.8082x + 3.9555
y = 0.8380x + 3.7225
y = 0.8537x + 3.9934
y = 0.8695x + 3.9062
y = 0.9103x + 4.128
y = 0.8735x + 3.9139
0.9876
0.9931
0.9706
0.9863
0.9759
0.9852
0.9797
54.9 1.4
19.6 2.3
33.5 2.3
15.1 0.9
18.1 1.5
9.1 2.7
E3
2,4‐di‐OCH3‐Ph
2,4‐di‐Cl‐Ph
Thiophen‐2‐yl
4‐Cl‐Ph
E11
E14
E15
E16
2‐Cl‐Ph
17.5 2.1
Bismerthiazol
‐
y = 0.8357x + 3.5466
FIGURE 1 SEM images for Xac after incubated in different concentration of compound E15
Xoo. When the substituent is a methoxy group, the bio-
logical activity of the compound at position 2 is superior
to Biological activity of compounds containing other
positions. When the substituent group R=4‐F‐Ph, the
target compound exhibits a good inhibitory activity
against Rs. When the substituent is a methoxy group,
the biological activity of the compound at position 2 is
superior to the biological activities of compounds at
other positions. When the substituent contains chlorine,
the target compound exhibits a good inhibitory activity
against Xac. At the same time, when the substituent is
a heterocyclic group and a halogen atom, the position
of the oxygen linkage is 4‐O, which has a better biolog-
ical activity.
had a phenomenon of invagination and dryness after
chemical treatment of 25 μg.mL‐1 E15. Figure 1(3) indi-
cates that the wall of the cells showed different degrees
of rupture after treatment with 50 μg.mL‐1 E15 solution,
and the content of the cells was leaked.
3 | CONCLUSIONS
In this work, we designed and synthesized 16 chalcone
derivatives containing thioether triazoles through a
five‐step reaction process with chalcone, 1,2‐
dibromoethane, and thiol triazole used as the starting
materials. The preliminary antibacterial activity tests
showed that the target compounds exhibit certain inhib-
itory activities against Xoo, Rs, and Xac. The EC50 values
of the target compounds against Xoo and Xac were
always better than the corresponding ones of commer-
cial agent bismerthiazol. SEM experiments showed that
the antibacterial mechanism of this type of compounds
against Xac may be attributed to the destruction of bac-
terial cell membrane structure, resulting in incomplete
bacterial structure, thus achieving the required
inhibition.
2.3 | Scanning electron microscope
experiment
(1) 0 μg.mL‐1, (2) 25 μg.mL‐1, and (3) 50 μg.mL‐1. Scale
bar for (1, 2, and 3) are 2 mm
The surface morphology of Xac was observed by SEM
(Figure 1). It was found that the cells in group Figure 1
(1) were rod‐shaped, uniform in size and intact in mor-
phology. As shown in Figure 1(2), the bacterial cell wall

CHEN ET AL.
5
4 | EXPERIMENTAL
4.1 | Instruments
4.6 | Preparation for target compounds
E1–E16
0.5 g of intermediate B (3.84 mmol), 1.33 g of K2CO3
(9.60 mmol), and 60 mL of DMF were added to a 100
mL round bottom flask, and stirred at room temperature
for 0.5 hr. Then 1.14 g of intermediate D (3.20 mmol)
was dissolved in DMF and added to the reaction system
and stirring was continued for 6‐8 h. When the reaction
was completed (monitored by TLC) the solution was dis-
persed in 100 mL water and extracted with ethyl acetate
(3×25 mL). The organic layer was collected and washed
with brine (3×30 mL), dried over anhydrous sodium sul-
fate, and the solvent was evaporated under reduced
pressure to give a crude product, which was purified
by column chromatography to give the pure title com-
pounds E1–E16.
1,2‐Dibromoethane, hydrazine hydrate, carbon disulfide,
and all solvents and reagents were purchased from
Shanghai Titan Scientific Co., Ltd and were of analytical
grade or chemically pure.
The melting point tests were conducted in an XT‐4
binocular microscope (Beijing Tech Instrument Co.). A
Bruker ASCEND 400 NMR spectrometer (BRUKER
OPTICS, Switzerland) were used for NMR analysis. A
QY‐20 three UV analyzer (Shanghai Anting Electronic
Instrument Factory) was used for thin layer chromatogra-
phy (TLC). The experimental measurements were carried
out on a Sartorius electronic balance (Sartorius Group,
Germany). SEM was carried out using an electron micro-
scope (FEI Nova Nano SEM 450).
4.6.1 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐
(thiophen‐2‐yl)prop‐2‐en‐1‐one (E1)
4.2 | Preparation for intermediate A[31]
1
Brown solid, yield 42%, M.P. 81.2‐82.4°С. H‐NMR (400
Hydrazinehydrate was dissolved in water at 50°C for 0.5
h, followed by the addition of carbon disulfide at 90°C
for 1 h. The solution was then cooled, followed
bycrystallization to obtain the intermediate A.
MHz, DMSO‐d6) δ 7.82‐7.12 (m, 9H, Ar–H), 5.88 (s, 2H,
NH2), 4.45 (t, J = 6.2 Hz, 2H, CH2), 3.56 (t, J = 6.1 Hz,
2H, CH2), 2.32 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 191.0, 157.3, 153.9, 151.1, 140.3, 135.5,
134.0, 133.3, 130.6, 130.5, 129.2, 128.8, 125.9, 121.5,
113.6, 67.4, 30.4, 10.2. ESI‐ HRMS m/z: 387.1 [M+H]+.
4.3 | Preparation for intermediate B[31]
4.6.2 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(4‐
fluorophenyl)prop‐2‐en‐1‐one (E2)
Intermediate A and glacial acetic acid were then refluxed
for 4 h, and then cooled to room temperature. Then, the
ureacted acetic acid was distilled off and the precipitate
washed with water to obtain intermediate B.
1
White solid, yield 38%, M.P. 95.2‐97.0°С. H‐NMR (400
MHz, DMSO‐d6) δ 7.96‐7.12 (m, 10H, Ar–H), 5.91 (s,
2H, NH2), 4.44 (t, J = 6.1 Hz, 2H, CH2), 3.55 (t, J = 6.1
Hz, 2H, CH2), 2.33 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 191.9, 162.5, 157.2, 153.9, 151.1, 141.4,
133.9, 131.7, 131.5, 130.5, 129.3, 127.1, 121.4, 116.5,
113.5, 67.2, 30.2, 10.2. ESI‐ HRMS m/z: 399.1 [M+H]+.
4.4 | Preparation for intermediate C[32–35]
Based on hydroxyacetophenone and various substituted
formaldehydes, intermediate C was synthesized under
alkaline and ice‐bath conditions.
4.6.3 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(2,4‐
dimethoxyphenyl)prop‐2‐en‐1‐one (E3)
4.5 | Preparation for intermediate
D[32,34,35]
1
Yellow solid, yield 28%, M.P. 88.2‐89.7°С. H‐NMR (400
Intermediate C and acetonitrile were refluxed for 1 hour,
then 1,2‐dibromoethane was added and refluxed for 7h.
Finally, it was extracted with ethyl acetate and distilled
under reduced pressure to obtain intermediate D.
MHz, DMSO‐d6) δ 7.86‐6.60 (m, 9H, Ar–H), 5.88 (s, 2H,
NH2), 4.42 (t, J = 6.3 Hz, 2H, CH2), 3.91 (s, 3H, CH3),
3.86 (s, 3H, CH3), 3.52 (t, J = 6.2 Hz, 2H, CH2), 2.32 (s,
3H, CH3). 13C‐NMR (101 MHz, DMSO‐d6) δ 192.3,

6
CHEN ET AL.
163.4, 160.3, 156.9, 153.9, 151.13, 137.7, 133.4, 130.4,
130.3, 129.8, 124.7, 121.4, 116.2, 113.6, 106.9, 98.8, 67.3,
56.3, 56.0, 30.2, 10.2. ESI‐ HRMS m/z: 441.2 [M+H]+.
151.1, 134.4, 131.5, 130.7, 129.2, 128.6, 128.5, 121.5, 113.6,
67.4, 30.4, 15.9, 10.3. ESI‐ HRMS m/z: 402.1 [M+H]+.
4.6.8 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐
(furan‐2‐yl)prop‐2‐en‐1‐one (E8)
4.6.4 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(3‐
nitrophenyl)prop‐2‐en‐1‐one (E4)
1
Brown solid, yield 29%, M.P. 85.1‐86.7°С. H‐NMR (400
Brown solid, yield 32%, M.P. 117.3‐118.9°С. 1H‐NMR (400
MHz, CDCl3) δ 8.80‐6.94 (m, 10H, Ar–H), 4.66 (s, 2H,
NH2), 4.39 (t, J = 5.8 Hz, 2H, CH2), 3.61 (t, J = 5.7 Hz,
2H, CH2), 2.38 (s, 3H, CH3).13C‐NMR (101 MHz, CDCl3)
δ 200.0, 164.3, 157.4, 153.8, 150.9, 148.2, 135.4, 135.0,
133.8, 130.4, 129.8, 128.3, 127.7, 124.6, 121.3, 121.1,
112.6, 66.7, 31.5, 10.2. ESI‐ HRMS m/z: 426.1 [M+H]+.
MHz, DMSO‐d6) δ 7.90‐6.70 (m, 9H, Ar–H), 5.88 (s, 2H,
NH2), 4.43 (t, J = 6.2 Hz, 2H, CH2), 3.53 (t, J = 6.2 Hz,
2H, CH2), 2.32 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 191.4, 157.2, 153.9, 151.5, 151.2, 146.6,
133.8, 130.4, 129.5, 129.0, 124.4, 121.5, 117.1, 113.7,
113.5, 67.4, 30.2, 10.2. ESI‐ HRMS m/z: 371.1 [M+H]+.
4.6.9 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(3,4‐
dimethoxyphenyl)prop‐2‐en‐1‐one (E9)
4.6.5 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(2‐
methoxyphenyl)prop‐2‐en‐1‐one (E5)
1
Yellow solid, yield 31%, M.P. 95.4‐96.8°С. H‐NMR (400
1
Yellow solid, yield 45%, M.P. 76.6‐77.5°С. H‐NMR (400
MHz, DMSO‐d6) δ 7.55‐7.01 (m, 9H, Ar–H), 5.84 (s, 2H,
NH2), 4.40 (t, J = 6.2 Hz, 2H, CH2), 3.82 (s, 6H, 2CH3),
3.51 (t, J = 6.2 Hz, 2H, CH2), 2.29 (s, 3H, CH3). 13C‐
NMR (101 MHz, DMSO‐d6) δ 192.2, 157.0, 153.9, 151.5,
151.1, 149.4, 143.4, 133.5, 130.3, 129.6, 127.8, 125.2,
123.8, 121.4, 113.6, 112.1, 111.0, 67.3, 56.0, 55.8, 30.3,
10.2. ESI‐ HRMS m/z: 441.2 [M+H]+.
MHz, DMSO‐d6) δ 7.91‐7.00 (m, 10H, Ar–H), 5.86 (s,
2H, NH2), 4.40 (t, J = 6.2 Hz, 2H, CH2), 3.87 (s, 3H,
CH3), 3.50 (t, J = 6.1 Hz, 2H, CH2), 2.29 (s, 3H, CH3).
13C‐NMR (101 MHz, DMSO‐d6) δ 192.3, 158.6, 157.1,
153.9, 151.1, 137.3, 133.7, 132.6, 130.4, 129.5, 128.8,
127.2, 123.3, 121.4, 121.3, 113.6, 112.2, 67.3, 56.2, 30.2,
10.2. ESI‐ HRMS m/z: 411.1 [M+H]+.
4.6.10 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(4‐
bromophenyl)prop‐2‐en‐1‐one (E10)
4.6.6 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(4‐
methoxyphenyl)prop‐2‐en‐1‐one (E6)
White solid, yield 41%, M.P. 149.3‐150.7°С. 1H‐NMR (400
MHz, DMSO‐d6) δ 7.83‐7.11 (m, 10H, Ar–H), 5.91 (s, 2H,
NH2), 4.44 (t, J = 6.0 Hz, 2H, CH2), 3.55 (t, J = 6.0 Hz,
2H, CH2), 2.33 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 191.9, 157.3, 153.9, 151.1, 141.1, 134.3,
134.1, 132.4, 131.1, 130.5, 129.1, 127.9, 124.3, 121.5,
113.5, 67.2, 30.2, 10.2. ESI‐ HRMS m/z: 459.0 [M+H]+.
1
Yellow solid, yield 31%, M.P. 93.2‐94.9°С. H‐NMR (400
MHz, DMSO‐d6) δ 7.78‐6.99 (m, 10H, Ar–H), 5.87 (s,
2H, NH2), 4.40 (t, J = 6.1 Hz, 2H, CH2), 3.81 (s, 3H,
CH3), 3.51 (t, J = 6.1 Hz, 2H, CH2), 2.29 (s, 3H, CH3).
13C‐NMR (101 MHz, DMSO‐d6) δ 192.0, 161.7, 157.0,
153.9, 151.1, 142.8, 133.6, 131.1, 130.4, 129.6, 127.6,
124.9, 121.4, 114.9, 113.5, 67.2, 55.8, 30.2, 10.2. ESI‐
HRMS m/z: 411.1 [M+H]+.
4.6.11 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(2,4‐
dichlorophenyl)prop‐2‐en‐1‐one (E11)
4.6.7 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(4‐
methylthiazol‐5‐yl)prop‐2‐en‐1‐one (E7)
White solid, yield 26%, M.P. 126.3‐127.7°С. 1H‐NMR (400
MHz, DMSO‐d6) δ 8.17‐7.12 (m, 9H, Ar–H), 5.90 (s, 2H,
NH2), 4.44 (t, J = 6.0 Hz, 2H, CH2), 3.55 (t, J = 6.0 Hz,
2H, CH2), 2.32 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 191.6, 157.4, 153.9, 151.0, 135.9, 135.7, 135.5,
134.4, 131.7, 130.6, 130.3, 130.0, 129.9, 128.7, 128.5, 121.5,
113.6, 67.2, 30.2, 10.2. ESI‐ HRMS m/z: 449.1 [M+H]+.
Brown solid, yield 27%, M.P. 130.3‐131.9°С. 1H‐NMR (400
MHz, DMSO‐d6) δ 9.15‐7.11(m, 7H, Ar–H), 5.97 (s, 2H,
NH2), 4.44 (t, J = 6.0 Hz, 2H, CH2), 3.55 (d, J = 5.9 Hz,
2H, CH2), 2.56 (s, 3H, CH3), 2.33 (s, 3H, CH3). 13C‐NMR
(101 MHz, DMSO‐d6) δ 190.4, 157.5, 157.0, 155.4, 154.0,

CHEN ET AL.
7
4.6.12 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(3‐
bromophenyl)prop‐2‐en‐1‐one (E12)
4.6.16 | (E)‐1‐(4‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(2‐
chlorophenyl)prop‐2‐en‐1‐one (E16)
1
Yellow solid, yield 49%, M.P. 63.6‐64.9°С. H‐NMR (400
White solid, yield 59%, M.P. 168.0‐169.4°С. 1H‐NMR (400
MHz, DMSO‐d6) δ 8.17‐7.16 (m, 10H, Ar–H), 5.88 (s, 2H,
NH2), 4.41 (t, J = 6.4 Hz, 2H, CH2), 3.54 (t, J = 6.3 Hz,
2H, CH2), 2.31 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 187.6, 162.7, 153.9, 151.1, 134.8, 133.0,
131.6, 130.9, 129.5, 125.4, 124.5, 122.9, 122.8, 116.7,
115.1, 67.0, 30.1, 10.2. ESI‐ HRMS m/z: 415.1 [M+H]+.
MHz, CDCl3) δ 7.78‐6.95 (m, 10H, Ar–H), 4.57 (s, 2H,
NH2), 3.34 (t, J = 5.8 Hz, 2H, CH2), 2.99 (t, J = 5.8 Hz,
2H, CH2), 2.38 (s, 3H, CH3). 13C‐NMR (101 MHz, CDCl3)
δ 192.7, 157.1, 153.8, 144.1, 141.4, 137.2, 133.7, 131.5,
130.3, 130.0, 129.0, 128.3, 127.4, 122.3, 121.4, 121.2,
112.5, 66.5, 29.9, 10.2. ESI‐ HRMS m/z: 459.0 [M+H]+.
4.7 | In vitro antibacterial activity
test[33,36]
4.6.13 | (E)‐1‐(2‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(3‐
(trifluoromethyl)phenyl)prop‐2‐en‐1‐one
(E13)
In this study, a series of novel chalcone derivatives con-
taining thioether triazole were synthesized and their anti-
bacterial activity against Xac, Rs and Xoo in vitro were
investigated using turbidity tests.
1
Yellow solid, yield 52%, M.P. 66.1‐68.0°С. H‐NMR (400
MHz, DMSO‐d6) δ 8.22‐7.11 (m, 10H, Ar–H), 5.85 (s,
2H, NH2), 4.42 (t, J = 6.1 Hz, 2H, CH2), 3.51 (t, J = 6.1
Hz, 2H, CH2), 2.30 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 192.0, 157.4, 153.9, 150.9, 143.3, 140.7,
136.3, 134.1, 132.3, 130.5, 129.7, 129.2, 129.0, 128.3,
127.0, 126.1, 121.5, 113.6, 67.3, 30.3, 10.2. ESI‐ HRMS
m/z: 449.1 [M+H]+.
4.8 | SEM imaging experiment[32]
The potential mechanism of E15 on Xanthomonas
axonopodis pv. citri (Xac) bacterial solution was deter-
mined by SEM.
ACKNOWLEDGMENT
4.6.14 | (E)‐1‐(4‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐
(thiophen‐2‐yl)prop‐2‐en‐1‐one (E14)
The authors gratefully acknowledge the financial support
of the National Key Research and Development Program
of China (No. 2017YFD0200506) and the National Nature
Science Foundation of China (No. 21462012).
1
Gray solid, yield 32%, M.P. 140.1‐141.5°С. H‐NMR (400
MHz, DMSO‐d6) δ 8.11‐7.12 (m, 9H, Ar–H), 5.88 (s, 2H,
NH2), 4.39 (t, J = 6.3 Hz, 2H, CH2), 3.53 (t, J = 6.3 Hz,
2H, CH2), 2.30 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 187.3, 162.5, 153.9, 151.1, 140.3, 136.5,
133.0, 131.3, 131.0, 130.7, 129.2, 120.7, 115.0, 67.0, 30.1,
10.3. ESI‐ HRMS m/z: 387.1 [M+H]+.
CONFLICT OF INTEREST
Authors declare no competing financial interest.
AUTHOR CONTRIBUTION
All authors have given approval to the final version of the
manuscript.
4.6.15 | (E)‐1‐(4‐(2‐((4‐amino‐5‐methyl‐4H‐
1,2,4‐triazol‐3‐yl)thio)ethoxy)phenyl)‐3‐(4‐
chlorophenyl)prop‐2‐en‐1‐one (E15)
ORCID
White solid, yield 73%, M.P. 115.8‐116.9°С. 1H‐NMR (400
MHz, DMSO‐d6) δ 8.20‐7.16 (m, 10H, Ar–H), 5.89 (s, 2H,
NH2), 4.42 (t, J = 6.3 Hz, 2H, CH2), 3.55 (t, J = 6.3 Hz,
2H, CH2), 2.31 (s, 3H, CH3). 13C‐NMR (101 MHz,
DMSO‐d6) δ 187.6, 162.8, 153.9, 151.1, 138.3, 134.8,
132.3, 131.7, 130.5, 129.1, 128.2, 125.2, 115.1, 67.0, 30.1,
10.2. ESI‐ HRMS m/z: 415.1 [M+H]+.
Wei Xue https://orcid.org/0000-0003-4471-5414
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