Synthesis and antibacterial evaluation of novel chalcone derivatives containing a benzothiazole scaffold

Article abstract of DOI:10.1007/s00706-019-02399-2

Abstract: A series of novel chalcone derivatives containing a benzothiazole scaffold were synthesized to develop novel antibacterial agents for solving the problem of drug resistance. Most compounds exhibited excellent antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), and Ralstonia solanacearum (Rs) compared to a reference drug, bismerthiazol. The results indicated that chalcone derivatives containing a benzothiazole scaffold merit more research as promising antibacterial agents. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-019-02399-2

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-019-02399-2
ORIGINAL PAPER
Synthesis and antibacterial evaluation of novel chalcone derivatives
containing a benzothiazole scafold
Yihui Wang1 · Pu Li1 · Shichun Jiang1 · Ying Chen1 · Shijun Su1 · Jun He1 · Mei Chen1 · Juping Zhang1 · Weiming Xu1 ·
Ming He1 · Wei Xue1
Received: 15 December 2018 / Accepted: 19 February 2019
© Springer-Verlag GmbH Austria, part of Springer Nature 2019
Abstract
A series of novel chalcone derivatives containing a benzothiazole scafold were synthesized to develop novel antibacterial
agents for solving the problem of drug resistance. Most compounds exhibited excellent antibacterial activity against Xan-
thomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), and Ralstonia solanacearum (Rs) compared
to a reference drug, bismerthiazol. The results indicated that chalcone derivatives containing a benzothiazole scafold merit
more research as promising antibacterial agents.
Graphical abstract
Keywords Synthesis · Chalcone · Benzothiazole · Antibacterial activity
Introduction
developing novel agrochemicals remains a huge challenge
for pesticide scientists [2, 3].
Plant pathogens Xanthomonas oryzae pv. Oryzae (Xoo),
Xanthomonas axonopodis pv. Citri (Xac), and Ralstonia
solanacearum (Rs) contribute to significant agriculture
losses every year [1]. Although conventional agrochemicals
have been efective, resistance develops quickly. Therefore,
Chalcone, a natural product, is widely used in a variety of
drugs. Previous research studies have used chalcone deriva-
tives for their bioactivities, antibacterial [4–6], antiviral
[7–9], insecticidal [10], anticancer [11], antifungal [12],
antiproliferative [13], and antioxidant [14] properties. Two
series of chalcone derivatives based on sulfone and bisulfate
have been demonstrated to have excellent antifungal activity
against C. albicans and great antibacterial activity against
S. typhimurium [15]. Some fuorinated chalcone–triazole
hybrids have also noteworthy efects against bacteria and
fungi [16].
Pu Li: co-frst author for this manuscript.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-019-02399-2) contains
supplementary material, which is available to authorized users.
Benzothiazole, a fused heterocycle, is a widely used
pesticide due to its antibacterial [17, 18], antiviral [19],
herbicidal [20], antifungal [21], antimicrobial [22–24],
antitumour [25], antiproliferative [26], antitubercular [27],
and anti-infammatory [28] properties. Many pesticides are
related to benzothiazole, such as the antiviral agent dufulin,
benzthiazuron herbicide, tribunal, and mefenacet. In addi-
tion, one hybrid containing 2-aminobenzothiazole and sub-
stituted aryl azides showed twice the antibacterial activity
* Ming He
mhe1@gzu.edu.cn
* Wei Xue
wxue@gzu.edu.cn
1
Key Laboratory of Green Pesticide and Agricultural
Bioengineering, Ministry of Education, Research
and Development Center for Fine Chemicals, Guizhou
University, Guiyang 550025, China
Vol.:(0123456789)
1 3

Y. Wang et al.
Table 1 Physical properties of compounds 2a–2q
against all Gram-positive bacteria and Gram-negative bac-
teria strains compared to ciprofoxacin [29]. The bioassay
results exerted that the types of fve member heterocyclic
compounds bearing a benzothiazole moiety showed better
antibacterial activity, compared to that containing an oxazole
moiety [30].
Compound Formula
Appearance
Yield/% M.p./°C
1c
1o
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
C14H11NO2
C19H13BrO2
C21H14N2O2S
C22H14ClNO2S White solid
White solid
White solid
White solid
89
79
80
68
78
68
51
58
82
>320
244–245
144–146
147–149
253–255
99–101
103–105
93–95
133–135
115–117
143–145
111–113
124–126
112–114
182–184
156–158
>320
Chalcone and benzothiazole possess many biological
properties and are widely used in drug development. How-
ever, there are few reports on the combination of both chal-
cone and benzothiazole and its efects on antibacterial activ-
ity. Therefore, in this paper, we introduced a benzothiazole
group into chalcone and investigated the antibacterial activ-
ity of the new hybrids against Xoo, Xac, and Rs to identify
novel and high-efciency antibacterial drugs.
C21H14N2O2S
C23H17NO2S
C23H17NO2S
C25H21NO2S
C22H15NO2S
C24H19NO4S
C20H13NO2S2
C23H17NO3S
C23H17NO3S
C20H13NO3S
C22H14N2O4S
C22H14N2O4S
White solid
White solid
White solid
White solid
White solid
Yellow solid 52
White solid
White solid
White solid
Yellow solid 68
White solid 74
Yellow solid 72
75
64
51
Results and discussion
2m
2n
2o
2p
2q
A description of the synthesis route is listed in Scheme 1.
Based on previously published methods [31] for 4-hydroxy-
acetophenone, aldosterone condensation was performed in
an ice bath under alkali conditions to prepare compound 1
with various substitutions of formaldehyde, 4-chlorobenz-
aldehyde, 4-methylbenzaldehyde, benzaldehyde, 4-nitro-
benzaldehyde, and 2-pyridylaldehyde. Then, etherifcation
between 2-chlorobenzothiazole and compound 1 to produce
compound 2 was performed under acetonitrile as a solvent,
potassium carbonate as a catalyser and refuxing at 85 °C.
We attempted to use triethylamine and dimethyl formamide
for compound 2; however, the catalysts produced a low yield
and long reaction time compared to potassium carbonate. As
shown in Table 1, the title compounds were obtained with
yields of 49–82%.
C26H16BrNO2S White solid
C23H14F3NO2S White solid
C24H19NO2S
58
49
76
142–144
123–125
White solid
7.64 ppm, which contribute to the CO–CH and CO–C=CH,
respectively. In the 13C NMR spectra of compound 1c,
the strong absorption peak at 131.96 and 115.96 ppm are
attributed to the Ar(4-OH), and the strong absorption peak
at 150.78 and 122.93 ppm are attributed to the pyridine ring.
For the compound 1o, approximate characteristic peak val-
ues of 131.93 and 115.99 ppm are attributed to the Ar(4-
OH), and the peak values range from 135.18 to 126.28 ppm
contribute to the naphthalene nucleus. The 13C NMR spectra
of all title compounds exhibit two special lines at approxi-
mately 188.37 and 171.21 ppm, which are attributed to
the S–C=N and C=O group, respectively. In the 1H NMR
spectra, all the title compounds possess two sets of peaks at
approximately 7.48–7.44 ppm and 7.39–7.35 ppm, which
All structural characterizations of the new compounds
were performed via 1H NMR, 13C NMR, and HRMS, and
all the signals in the spectra are in agreement with the pro-
posed structure. The 1H NMR spectra of compounds 1c and
1o appear two distinct absorption peak at nearly 8.16 and
Scheme 1
1 3

Synthesis and antibacterial evaluation of novel chalcone derivatives containing a…
Table 3 EC50 values of target compounds against Xoo, Xac, and Rs
confrm the benzothiazole ring structure. The strong pres-
ence of [M+H]+ ions indicates that the title compounds are
in steady state.
Compound
R
EC50/µg/cm3
Xoo
Xac
Rs
2a
Pyridin-2-yl
4-ClPh
50.37
48.66
52.40
65.48
–
38.97
46.64
65.65
66.74
72.75
54.24
35.59
50.97
–
13.42
–
88.70
Antibacterial activity
2b
2c
Pyridin-4-yl
2,4-di-OMePh
Furan-2-yl
3-NO2Ph
4-NO2Ph
4-CF3Ph
36.49
64.64
Xoo (strain PXO99A, Nangjing Agricultural University,
China), Xac (strain 29-1, Shanghai Jiao Tong University,
China), and Rs (strain MR111, Guizhou University, China)
were used as test strains, commercial antibacterial agent
bismerthiazol was used as positive control, and DMSO was
used as a blank control. To determine the EC50 values of the
compounds, the antibacterial activity against Xoo, Xac, and
Rs was assessed by testing at fve concentrations (100, 50,
25, 12.5, and 6.25 µg/cm3).
2h
2l
2m
2n
–
2p
42.56
–
54.58
2q
3,4-di-MePh
–
Bismerthiazol
97.18
As shown in Tables 2 and 3, more title compounds exhib-
ited substantial antibacterial activity against Xoo, and the
fewest compounds exhibited excellent antibacterial activity
against Rs. The bioassay data analysis also indicated that the
antibacterial activity of the title compounds was dependent
on the R fragment.
cm3, respectively, which exceeded that of bismerthiazol
(54.58 μg/cm3).
Meanwhile, compounds 2h and 2q containing two elec-
tron groups (2,4-di-OMePh, 3,4-di-MePh) presented supe-
rior antibacterial activity. Compound 2h exhibited antibacte-
rial activity against Xoo and Rs, with EC50 values of 65.48
and 64.64 μg/cm3, respectively, which were better than that
of bismerthiazol (72.75 and 97.18 μg/cm3, respectively).
Compound 2q against Xoo with an EC50 value of 66.74 μg/
cm3, which outperformed that of bismerthiazol (72.75 μg/
cm3).
For example, when R was substituted by an electron-with-
drawing group (4-ClPh, 3-NO2Ph, 4-NO2Ph, and 4-CF3Ph),
corresponding compounds 2b, 2m, 2n, and 2p exhibited
antibacterial activity against Xoo, with EC50 values of
48.66, 38.97, 46.64, and 65.65 µg/cm3, respectively, which
exceeded that of bismerthiazol (72.75 µg/cm3). Compounds
2b and 2p also showed remarkable antibacterial activ-
ity against Xac, with EC50 values of 35.59 and 42.56 μg/
Pyridine fragments resulting in compounds 2a and 2c
with a broad spectrum and efcient antibacterial activ-
ity against Xoo with EC50 values of 50.37 and 52.40 μg/
Table 2 Inhibition (%) efect
Compound
Xoo
100 μg/cm3
Xac
100 μg/cm3
Rs
of the compounds against Xoo,
Xac, and Rs
50 μg/cm3
50 μg/cm3
100 μg/cm3
50 μg/cm3
2a
70
74
76
45
48
54
37
62
31
53
52
49
76
71
54
68
67
59
46
44
41
29
21
29
20
40
24
43
43
33
51
54
36
33
34
39
71
84
72
56
36
59
31
29
27
34
35
100
29
60
34
74
56
70
56
57
48
45
20
31
14
24
11
21
16
72
13
34
21
50
45
49
56
14
72
11
18
21
4
45
11
28
9
4
0
2
29
4
11
30
6
41
15
33
20
23
28
2b
2c
2d
2e
2f
2g
2h
77
7
2i
2j
27
36
18
48
34
37
24
25
52
2k
2l
2m
2n
2o
2p
2q
Bismerthiazol
1 3

Y. Wang et al.
cm3, respectively, which exceeded that of bismerthiazol
(72.75 μg/cm3). The activity against Xac resulted in EC50
values of 54.24 and 50.97 μg/cm3, respectively, which
outperformed that of bismerthiazol (54.58 μg/cm3). The
activity against Rs resulted in EC50 values of 88.70 and
36.49 μg/cm3, respectively, which were better than that of
bismerthiazol (97.18 μg/cm3).
General procedure for the synthesis of compounds
1a–1q
According to the synthetic method of the literature [31],
based on 4-hydroxyacetophenone and various substituted
formaldehyde, compounds 1 were prepared by the method
of aldosterone condensation, under the conditions both alka-
line and ice bath. All of them are known compounds except
1c and 1o, their physical and chemical properties are listed
in the electronic supplementary material.
Furthermore, compound 2l contained a furan moiety
and exhibited antibacterial activity against Xac, with an
EC50 value of 13.42 μg/cm3, which far surpassed that of
bismerthiazol (54.58 μg/cm3).
Interestingly, among all the title compounds, 2m, 2l,
and 2c exhibited the strongest antibacterial activity against
Xoo, Xac, and Rs, respectively, with EC50 values of 38.97,
13.42, and 36.49 μg/cm3, respectively, which far surpassed
that of bismerthiazol (72.75, 54.58, and 97.18 μg/cm3,
respectively).
(E)‑1‑(4‑Hydroxyphenyl)‑3‑(pyridin‑4‑yl)prop‑2‑en‑1‑one
(1c, C14H11NO2) White solid; yield: 89%; m.p.:>320 °C; 1H
NMR (400 MHz, DMSO-d6): δ = 8.67 (d, J = 4.9 Hz, 2H,
pyridine-3, 5-H), 8.16 (d, J = 16.1 Hz, 1H, CO–C = CH),
8.12 (d, J = 8.0 Hz, 2H, Ar(4-OH)-2, 6-H), 7.84 (d,
J = 5.1 Hz, 2H, pyridine-2, 6-H), 7.64 (d, J = 15.6 Hz,
1H, CO–CH), 6.93 (d, J = 8.0 Hz, 2H, Ar(4-OH)-3, 5-H)
ppm; 13C NMR (101 MHz, DMSO-d6): δ=187.37, 163.08,
150.78, 142.49, 140.30, 131.96, 131.19, 129.10, 126.88,
122.93, 115.96, 115.60 ppm; HRMS (ESI): m/z (calcd.)
[M+H]+ 226.0862, found 226.0858.
Conclusion
We report a series of novel chalcone derivatives that were
structurally confrmed via 1H NMR, 13C NMR, and HRMS
and evaluated for antibacterial activity against Xoo, Xac,
and Rs in vitro. Antibacterial screening results dem-
onstrated that compounds 2c, 2l, and 2m exhibited the
strongest antibacterial activity among all the title com-
pounds. Based on this study, chalcone derivatives contain-
ing benzothiazolyl deserve further research as a potential
agricultural fungicide.
(E)‑3‑(1‑Bromonaphthalen‑2‑yl)‑1‑(4‑hydroxyphenyl)‑
prop‑2‑en‑1‑one (1o, C19H13BrO2) White solid; yield:
79%; m.p.: 244–245 °C; 1H NMR (400 MHz, DMSO-d6):
δ = 8.34–8.26 (m, 3H, CO–C=CH, naphthalene-3, 5-H),
8.16 (d, J = 8.8 Hz, 2H, Ar(4-OH)-2, 6-H), 8.11–8.03 (m,
3H, naphthalene-6, 7, 8-H), 7.76–7.66 (m, 2H, CO–CH,
naphthalene-4-H), 6.95 (d, J = 8.7 Hz, 2H, Ar(4-OH)-3,
5-H) ppm; 13C NMR (101 MHz, DMSO-d6): δ = 187.31,
163.09, 141.50, 135.18, 132.84, 132.29, 131.93, 129.29,
128.96, 128.73, 128.52, 127.95, 126.83, 126.28, 125.29,
115.99 ppm; HRMS (ESI): m/z (calcd.) [M+H]+ 353.0171,
found 353.0159.
Experimental
A Bruker ASCEND 400 NMR spectrometer (BRUKER
OPTICS, Switzerland) was used to record the nuclear
magnetic resonance (NMR) spectra with tetramethylsi-
lane (TMS) as the internal standard and dimethylsulfoxide
(DMSO-d6, 2.50 ppm (1H), 39.50 ppm (13C)) or deutero-
chloroform (CDCl3, 7.26 ppm (1H), 76.00 ppm (13C)) as
the solvent. The melting point tests were conducted in an
XT-4 binocular microscope (Beijing Tech Instrument Co).
The measurements of all experiments were completed on a
Sartorius electronic balance (Sartorius Group, Germany).
A QY-20 three UV analyser (Shanghai Anting Electronic
Instrument Factory) was used for thin layer chromatog-
raphy (TLC). 2-Chlorobenzothiazole, 4-hydroxyaceto-
phenone, all solvents and reagents were purchased from
Shanghai Titan Scientifc Co., Ltd and were analytical
grade or chemically pure.
General procedure for the synthesis of title
compounds 2a–2q
Intermediates 1a (1.0 mmol) and 2-chlorobenzothiazole
(1.1 mmol) were added to a round-bottomed fask with
K2CO3 (1.5 mmol) and 20 cm3 acetonitrile as a solvent and
stirred at 85 °C for 3–5 h. After the reaction was complete,
the system was fltered with alcohol as a fushing fuid. A
sufcient amount of water was then added to the fltrate,
and liquid was separated under constantly stirring, suction
fltration, drying, and recrystallization from petroleum ether
to obtain the title compound 2a. Compounds 2b–2q were
prepared in the same way.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(pyridin‑2‑yl)‑
prop‑2‑en‑1‑one (2a, C21H14N2O2S) White solid; yield: 80%;
m.p.: 144–146 °C; 1H NMR (400 MHz, DMSO-d6): δ=8.72
1 3

Synthesis and antibacterial evaluation of novel chalcone derivatives containing a…
(t, J=5.2 Hz, 1H, pyridine-3-H), 8.31–8.24 (m, 2H, Ph-2,
6-H), 8.20 (dd, J = 15.5, 6.2 Hz, 1H, benzothiazole-4-H),
8.01 (dd, J=13.8, 6.4 Hz, 1H, benzothiazole-7-H), 7.93 (dd,
J=15.5, 6.9 Hz, 2H, CO–CH, CO–C=CH), 7.81–7.65 (m,
4H, benzothiazole-5, 6-H, pyridine-5, 6-H), 7.51–7.43 (m,
2H, Ph-3, 5-H), 7.39 (dd, J=14.1, 7.3 Hz, 1H, pyridine-4-H)
ppm; 13C NMR (101 MHz, DMSO-d6): δ=188.78, 171.12,
158.16, 153.20, 150.55, 148.77, 143.80, 137.72, 135.64,
132.47, 131.40, 127.11, 125.51, 125.41, 125.06, 122.87,
121.90, 121.47 ppm; HRMS (ESI): m/z (calcd.) [M + H]+
359.0848, found 359.0841.
129.51, 127.10, 125.02, 122.85, 121.87, 121.37, 121.30,
21.59 ppm; HRMS (ESI): m/z (calcd.) [M+H]+ 372.1052,
found 372.1047.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(m‑tolyl)‑
prop‑2‑en‑1‑one (2e, C23H17NO2S) White solid; yield: 51%;
m.p.: 103–105 °C; 1H NMR (400 MHz, CDCl3): δ=8.16–
8.12 (m, 2H, Ph-2, 6-H), 7.82 (d, J = 15.7 Hz, 1H, CO–
C=CH), 7.77 (dd, J=8.1, 0.5 Hz, 1H, benzothiazole-4-H),
7.72 (dd, J=8.0, 0.7 Hz, 1H, benzothiazole-7-H), 7.55–7.50
(m, 3H, Ph-3, 5-H, CO–CH), 7.46 (d, J=7.1 Hz, 2H, Ar(3-
CH3)-4, 6-H), 7.44–7.40 (m, 1H, benzothiazole-5-H), 7.35–
7.29 (m, 3H, benzothiazole-6-H, Ar(3-CH3)-2, 5-H), 2.41 (s,
3H, CH3) ppm; 13C NMR (101 MHz, CDCl3): δ=189.09,
170.58, 157.85, 148.83, 145.42, 138.71, 135.82, 134.75,
132.41, 131.59, 130.65, 129.12, 128.92, 126.46, 125.81,
124.51, 121.99, 121.49, 121.43, 120.36, 21.38 ppm; HRMS
(ESI): m/z (calcd.) [M+H]+ 372.1052, found 372.1046.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(4‑chlorophenyl)‑
prop‑2‑en‑1‑one (2b, C221H14ClNO2S) White solid; yield:
47%; m.p.: 143–145 °C; H NMR (400 MHz, DMSO-d6):
δ=8.33 (d, J=8.6 Hz, 2H, Ph-2, 6-H), 8.06–7.94 (m, 4H,
Ar(4-Cl)-2, 6-H, benzothiazole-4-H, CO–C=CH), 7.76 (dd,
J=19.1, 11.8 Hz, 2H, benzothiazole-7-H, CO–CH), 7.67 (d,
J=8.6 Hz, 2H, Ar(4-Cl)-3, 5-H), 7.55 (d, J=8.3 Hz, 2H, Ph-
3,5-H), 7.48–7.44 (m, 1H, benzothiazole-5-H), 7.39–7.35 (m,
1H, benzothiazole-6-H) ppm; 13C NMR (101 MHz, DMSO-
d6): δ = 188.31, 171.17, 158.09, 148.79, 143.28, 135.81,
135.68, 134.11, 132.45, 131.43, 131.17, 129.46, 127.11,
125.03, 123.11, 122.86, 121.88, 121.40 ppm; HRMS (ESI):
m/z (calcd.) [M+H]+ 392.0506, found 392.0497.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(4‑isopropyl‑
phenyl)prop‑2‑en‑1‑one (2f, C25H21NO2S) White solid;
yield: 58%; m.p.: 93–95 °C; 1H NMR (400 MHz, DMSO-
d6): δ = 8.34–8.29 (m, 2H, Ph-2, 6-H), 8.00 (dd, J = 8.0,
0.8 Hz, 1H, benzothiazole-4-H), 7.95 (d, J=15.6 Hz, 1H,
CO–C=CH), 7.84 (d, J = 8.2 Hz, 2H, Ar(4-iPr)-2, 6-H),
7.80–7.71 (m, 2H, benzothiazole-7-H, CO–CH), 7.69–7.64
(m, 2H, Ar(4-iPr)-3, 5-H), 7.50–7.42 (m, 1H, benzothiazole-
5-H), 7.42–7.32 (m, 3H, Ph-3, 5-H, benzothiazole-6-H),
3.00–2.89 (m, 1H, CH), 1.24 (s, 3H, CH3), 1.22 (s, 3H,
CH3) ppm; 13C NMR (101 MHz, DMSO-d6): δ = 188.40,
171.21, 157.96, 152.07, 148.80, 144.86, 136.05, 132.83,
132.45, 131.31, 129.63, 127.41, 127.10, 125.02, 122.85,
121.87, 121.42, 121.37, 33.93, 24.09 ppm; HRMS (ESI):
m/z (calcd.) [M+H]+ 400.1365, found 400.1357.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(pyridin‑4‑yl)‑
prop‑2‑en‑1‑one (2c, C21H14N2O2S) White solid; yield: 78%;
m.p.: 253–255 °C; 1H NMR (400 MHz, DMSO-d6): δ=8.70
(d, J = 6.0 Hz, 2H, pyridine-3, 5-H), 8.38–8.33 (m, 2H,
Ph-2, 6-H), 8.23 (d, J=15.7 Hz, 1H, CO–C=CH), 8.01 (dd,
J=8.0, 0.8 Hz, 1H, benzothiazole-4-H), 7.88 (dd, J=4.6,
1.4 Hz, 2H, pyridine-2, 6-H), 7.88 (dd, J = 4.6, 1.4 Hz,
2H, CO–CH, benzothiazole-7-H), 7.76–7.71 (m, 2H, Ph-3,
5-H), 7.49–7.44 (m, 1H, benzothiazole-5-H), 7.40–7.36 (m,
1.2 Hz, 1H, benzothiazole-6-H) ppm; 13C NMR (101 MHz,
DMSO-d6): δ = 188.37, 171.14, 158.28, 150.87, 148.76,
142.21, 141.78, 135.41, 132.46, 131.62, 127.12, 126.66,
125.05, 123.06, 122.88, 121.89, 121.50 ppm; HRMS (ESI):
m/z (calcd.) [M+H]+ 359.0848, found 359.0841.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑phenyl‑
prop‑2‑en‑1‑one (2g, C22H15NO2S) White solid; yield:
82%; m.p.: 133–135 °C; 1H NMR (400 MHz, DMSO-d6):
δ = 8.35–8.31 (m, 2H, Ph-2, 6-H), 8.05 (d, J = 15.6 Hz,
1H, CO–C=CH), 8.00 (dd, J = 8.0, 0.7 Hz, 1H, benzothi-
azole-4-H), 7.89 (d, J = 8.5 Hz, 2H, Ar-2, 6-H), 7.75 (t,
J = 11.6 Hz, 2H, CO–CH, benzothiazole-7-H), 7.70–7.66
(m, 4H, Ph-3, 5-H, Ar-3, 5-H), 7.48–7.44 (m, 1H, benzothi-
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(p‑tolyl)‑
prop‑2‑en‑1‑one (2d, C23H17NO2S) White solid; yield: 68%;
m.p.: 99–101 °C; 1H NMR (400 MHz, DMSO-d6): δ=8.32
(d, J=8.8 Hz, 2H, Ph-2, 6-H), 8.00 (dd, J=8.0, 0.7 Hz, 1H,
benzothiazole-4-H), 7.95 (d, J=15.6 Hz, 1H, CO–C=CH),
7.82 (d, J = 8.1 Hz, 2H, Ar(4-CH3)-2, 6-H), 7.79–7.72
(m, 2H, CO–CH, benzothiazole-7-H), 7.67 (d, J=8.8 Hz,
2H, Ar(4-CH3)-3, 5-H), 7.49–7.42 (m, 1H, benzothiazole-
5-H), 7.40–7.35 (m, 1H, benzothiazole-6-H), 7.30 (d,
J=8.0 Hz, 2H, Ph-3, 5-H), 2.37 (s, 3H, CH3) ppm; 13C NMR
(101 MHz, DMSO-d6): δ=188.37, 171.21, 157.96, 148.80,
144.86, 141.33, 136.04, 132.45, 132.41, 131.32, 130.05,
azole-5-H), 7.40–7.35 (m, 1H, benzothiazole-6-H) ppm; 13
C
NMR (101 MHz, DMSO-d6): δ = 188.32, 171.17, 158.09,
148.79, 143.37, 135.80, 134.43, 132.45, 132.38, 131.43,
131.36, 127.10, 125.03, 124.59, 123.15, 122.86, 121.88,
121.40 ppm; HRMS (ESI): m/z (calcd.) [M+H]+ 380.0715,
found 380.0700.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(2,4‑dimeth‑
oxyphenyl)prop‑2‑en‑1‑one (2h, C24H19NO4S) Yellow
solid; yield: 52%; m.p.: 115–117 °C; 1H NMR (400 MHz,
1 3

Y. Wang et al.
DMSO-d6): δ = 8.52–8.48 (m, 2H, Ph-2, 6-H), 8.37 (d,
J=15.6 Hz, 1H, CO–C=CH), 8.18–8.14 (m, 1H, benzothi-
azole-4-H), 8.08 (d, J=8.6 Hz, 1H, Ar(2, 4-di-OCH3)-6-H),
8.04 (d, J=15.7 Hz, 1H, CO–CH), 7.95–7.92 (m, 1H, benzo-
thiazole-7-H), 7.88–7.84 (m, 2H, Ph-3, 5-H), 7.72–7.67 (m,
1H, benzothiazole-5-H), 7.64–7.56 (m, 1H, benzothiazole-
6-H), 6.90 (d, J=2.3 Hz, 1H, Ar(2, 4-di-OCH3)-3-H), 6.86
(dd, J = 8.7, 2.3 Hz, 1H, Ar(2, 4-di-OCH3)-5-H), 4.20 (s,
3H, OCH3), 4.12 (s, 3H, OCH3) ppm; 13C NMR (101 MHz,
DMSO-d6): δ = 198.56, 181.29, 174.17, 171.10, 168.24,
159.55, 150.13, 147.08, 142.98, 141.29, 140.96, 140.91,
137.06, 135.07, 132.44, 132.12, 131.13, 129.59, 127.08,
125.76, 116.72, 108.67, 65.85, 65.61 ppm; HRMS (ESI):
m/z (calcd.) [M+H]+ 418.1107, found 418.1101.
benzothiazole-5-H), 7.35–7.29 (m, 1H, benzothiazole-6-H),
6.95 (d, J=8.8 Hz, 2H, Ph-3, 5-H), 3.87 (s, 3H, OCH3) ppm;
13C NMR (101 MHz, CDCl3): δ=189.10, 170.65, 161.82,
157.71, 148.84, 145.08, 136.09, 132.41, 130.55, 130.34,
127.53, 126.45, 124.49, 121.98, 121.43, 120.32, 119.36,
114.49, 55.46 ppm; HRMS (ESI): m/z (calcd.) [M + H]+
388.1001, found 388.0994.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(furan‑2‑yl)‑
prop‑2‑en‑1‑one (2l, C20H13NO3S) Yellow solid; yield:
1
68%; m.p.: 112–114 °C; H NMR (400 MHz, CDCl3):
δ=8.17–8.12 (m, 2H, Ph-2, 6-H), 7.76 (d, J =8.1 Hz, 1H,
benzothiazole-4-H), 7.72 (dd, J=8.0, 0.6 Hz, 1H, benzothia-
zole-7-H), 7.63 (d, J=15.3 Hz, 1H, CO–C=CH), 7.56–7.48
(m, 4H, Ph-3, 5-H, CO–CH, furan-3-H), 7.44–7.39 (m, 1H,
benzothiazole-5-H), 7.33–7.29 (m, 1H, benzothiazole-6-H),
6.75 (d, J=3.4 Hz, 1H, furan-5-H), 6.56–6.50 (m, 1H, furan-
4-H) ppm; 13C NMR (101 MHz, CDCl3): δ=188.35, 170.59,
157.86, 151.62, 148.83, 145.09, 135.73, 132.41, 130.97,
130.57, 126.45, 124.50, 121.99, 121.43, 120.35, 118.89,
116.58, 112.78 ppm; HRMS (ESI): m/z (calcd.) [M + H]+
364.0460, found 364.0452.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(thiophen‑2‑yl)‑
prop‑2‑en‑1‑one (2i, C20H13NO2S2) White solid; yield:
1
75%; m.p.: 143–145 °C; H NMR (400 MHz, CDCl3):
δ=8.15–8.10 (m, 2H, Ph-2, 6-H), 7.98 (d, J=15.3 Hz, 1H,
CO–C=CH), 7.77 (d, J=7.7 Hz, 1H, thiophene-3-H), 7.72
(dd, J=8.0, 0.6 Hz, 1H, thiophene-5-H), 7.55–7.51 (m, 2H,
Ph-3, 5-H), 7.45–7.29 (m, 5H, CO–CH, benzothiazole-4,
5, 6, 7-H), 7.11 (dd, J = 5.0, 3.7 Hz, 1H, thiophene-4-H)
ppm; 13C NMR (101 MHz, CDCl3): δ = 188.50, 170.66,
157.94, 148.90, 140.40, 137.65, 135.76, 132.48, 132.43,
130.63, 129.12, 128.53, 126.54, 124.59, 122.07, 121.51,
120.45 ppm; HRMS (ESI): m/z (calcd.) [M+H]+ 364.0452,
found 364.0460.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(3‑nitrophenyl)‑
prop‑2‑en‑1‑one (2m, C22H14N2O4S) White solid; yield:
1
74%; m.p.: 182–184 °C; H NMR (400 MHz, CDCl3):
δ=8.53 (s, 1H, Ar(3-NO2)-2-H), 8.28 (dd, J=8.2, 1.2 Hz,
1H, benzothiazole-4-H), 8.17 (d, J = 8.8 Hz, 2H, Ph-2,
6-H), 7.94 (d, J = 7.6 Hz, 1H, Ar(3-NO2)-4-H), 7.87 (d,
J = 15.7 Hz, 1H, CO–C=CH), 7.75 (dd, J = 13.5, 8.0 Hz,
2H, benzothiazole-7-H, Ar(3-NO2)-6-H), 7.69–7.61 (m, 2H,
CO–CH, Ar(3-NO2)-5-H), 7.58 (d, J = 8.8 Hz, 2H, Ph-3,
5-H), 7.45–7.41 (m, 1H, benzothiazole-5-H), 7.35–7.31 (m,
1H, benzothiazole-6-H) ppm; 13C NMR (101 MHz, CDCl3):
δ=188.18, 170.38, 158.24, 148.77, 141.97, 136.57, 135.05,
134.40, 132.41, 130.78, 130.12, 126.50, 124.80, 124.59,
124.25, 122.40, 122.02, 121.45, 120.50 ppm; HRMS (ESI):
m/z (calcd.) [M+H]+ 403.0747, found 403.0738.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(2‑methoxyphe‑
nyl)prop‑2‑en‑1‑one (2j, C23H17NO3S) White solid; yield:
1
64%; m.p.: 111–113 °C; H NMR (400 MHz, CDCl3):
δ = 8.17–8.11 (m, 3H, Ph-2, 6-H, CO–C=CH), 7.76 (d,
J=8.1 Hz, 1H, benzothiazole-4-H), 7.73–7.70 (m, 1H, ben-
zothiazole-7-H), 7.66–7.61 (m, 2H, CO–CH, Ar(2-OCH3)-
6-H), 7.54–7.49 (m, 2H, Ph-3, 5-H), 7.44–7.36 (m, 2H,
benzothiazole-5-H, Ar(2-OCH3)-4-H), 7.33–7.28 (m, 1H,
benzothiazole-6-H), 7.00 (t, J=7.5 Hz, 1H, Ar(2-OCH3)-
5-H), 6.95 (d, J = 8.3 Hz, 1H, Ar(2-OCH3)-3-H), 3.92 (s,
3H, OCH3) ppm; 13C NMR (101 MHz, CDCl3): δ=189.67,
170.67, 158.91, 157.71, 148.85, 140.81, 136.12, 132.41,
131.94, 130.67, 129.45, 126.45, 124.49, 123.82, 122.53,
121.97, 121.44, 120.81, 120.29, 111.28, 55.59 ppm; HRMS
(ESI): m/z (calcd.) [M+H]+ 388.1001, found 388.0990.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(4‑nitrophenyl)‑
prop‑2‑en‑1‑one (2n, C22H14N2O4S) Yellow solid; yield:
1
72%; m.p.: 156–158 °C; H NMR (400 MHz, CDCl3):
δ = 8.29 (d, J = 8.8 Hz, 2H, Ar(4-NO2)-3, 5-H), 8.15 (d,
J=8.8 Hz, 2H, Ar(4-NO2)-2, 6-H), 7.85 (d, J=15.7 Hz, 1H,
CO–C=CH), 7.80 (d, J=8.7 Hz, 2H, Ph-2, 6-H), 7.78–7.72
(m, 2H, benzothiazole-4, 7-H), 7.64 (d, J = 15.7 Hz, 1H,
CO–CH), 7.57 (d, J=8.8 Hz, 2H, Ph-3, 5-H), 7.45–7.41 (m,
1H, benzothiazole-5-H), 7.35–7.31 (m, 1H, benzothiazole-
6-H) ppm; 13C NMR (101 MHz, CDCl3): δ=188.20, 170.39,
158.26, 148.71, 148.64, 141.86, 140.93, 134.98, 132.39,
130.78, 129.02, 126.53, 125.34, 124.64, 124.28, 121.99,
121.48, 120.51 ppm; HRMS (ESI): m/z (calcd.) [M + H]+
403.0747, found 403.0737.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(4‑methoxy‑
phenyl)prop‑2‑en‑1‑one (2k, C23H17NO3S) White solid;
yield: 51%; m.p.: 124–126 °C; 1H NMR (400 MHz, CDCl3):
δ = 8.16–8.10 (m, 2H, Ph-2, 6-H), 7.82 (d, J = 15.6 Hz,
1H, CO–C=CH), 7.79–7.75 (m, 1H, benzothiazole-4-H),
7.72 (dd, J = 8.0, 0.6 Hz, 1H, benzothiazole-7-H), 7.62
(d, J = 8.7 Hz, 2H, Ar(4-OCH3)-2, 6-H), 7.55–7.50 (m,
2H, Ar(4-OCH3)-3, 5-H), 7.45–7.40 (m, 2H, CO–CH,
1 3

Synthesis and antibacterial evaluation of novel chalcone derivatives containing a…
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(1‑bromo‑
naphthalen‑2‑yl)prop‑2‑en‑1‑one (2o, C26H16BrNO2S) White
were dissolved in DMSO and diluted with sterile distilled
water. DMSO was diluted with sterile distilled water
for a blank control. 1 cm3 of the liquid sample contain-
ing tested compounds or bismerthiazol was added to
4 cm3 of the nutrient broth medium (NB: 6 g beef extract,
10 g peptone, 2 g yeast powder, 20 g glucose, and 2 dm3
distilled water, pH 7.0–7.2). Then, 40 mm3 of NB con-
taining Xoo, Xac, or Rs was added to 5 cm3 of the NB
containing test compounds or bismerthiazol. The inocu-
lated test tubes were incubated at 28 1 °C under con-
tinuous shaking at 180 rpm for 24–48 h. The culture
growth was monitored on a spectrophotometer at 600 nm
(OD600) and expressed as corrected turbidity. The formula,
I(%) = (Ctur − Ttur)∕Ctur × 100, was used for calculating
the relative inhibitory rate (I, %). Ctur represents the cor-
rected turbidity value of bacterial growth on the blank
control, and Ttur denotes the corrected turbidity value of
bacterial growth on treated NB.
1
solid; yield: 58%; m.p.: > 320 °C; H NMR (400 MHz,
CDCl3): δ=8.52 (d, J=15.7 Hz, 1H, CO–C=CH), 8.41 (d,
J=8.3 Hz, 1H, naphthalene-3-H), 8.21–8.16 (m, 2H, Ph-2,
6-H), 7.88–7.72 (m, 5H, benzothiazole-4, 7-H, naphthalene-6,
7, 8-H), 7.66–7.60 (m, 2H, naphthalene-4, 5-H), 7.59–7.52
(m, 3H, CO–CH, Ph-3, 5-H), 7.45–7.40 (m, 1H, benzothia-
zole-5-H), 7.35–7.30 (m, 1H, benzothiazole-6-H) ppm; 13
C
NMR (101 MHz, CDCl3): δ=188.97, 170.52, 158.00, 148.81,
144.57, 135.53, 135.08, 132.71, 132.55, 132.42, 130.82,
128.39, 128.23, 128.16, 128.12, 127.94, 127.82, 126.48,
125.06, 124.54, 123.94, 122.01, 121.44, 120.40 ppm; HRMS
(ESI): m/z (calcd.) [M+H]+ 486.0157, found 486.0149.
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑[4‑(trifuoromethyl)‑
phenyl]prop‑2‑en‑1‑one (2p, C23H14F3NO2S) White solid;
yield: 49%; m.p.: 142–144 °C; 1H NMR (400 MHz, CDCl3):
δ=8.18–8.12 (m, 2H, Ph-2, 6-H), 7.85 (d, J=15.7 Hz, 1H,
CO–C=CH), 7.79–7.72 (m, 4H, Ar(4-CF3)-2, 6-H, benzo-
thiazole-4, 7-H), 7.69 (d, J=8.4 Hz, 2H, Ar(4-CF3)-3, 5-H),
7.63–7.58 (m, 1H, CO–CH), 7.57–7.54 (m, 2H, Ph-3, 5-H),
7.45–7.41 (m, 1H, benzothiazole-5-H), 7.35–7.32 (m, 1H,
benzothiazole-6-H) ppm; 13C NMR (101 MHz, CDCl3):
δ=188.57, 170.45, 158.11, 148.77, 143.08, 138.17, 135.26,
132.40, 130.73, 128.58, 126.50, 126.00, 125.96, 124.58,
123.86, 122.00, 121.46, 120.46 ppm; 19F NMR (376 MHz,
CDCl3): δ = − 62.84 ppm; HRMS (ESI): m/z (calcd.)
[M+H]+ 426.0770, found 426.0759.
Some compounds were tested against Xoo, Xac, and
Rs under diferent concentrations (100, 50, 25, 12.5, and
6.25 μg/cm3) to obtain the EC50 values. EC50 values were
determined using SPSS17.0, and the experiments were
repeated three times.
Acknowledgements The authors gratefully acknowledge the fnancial
support of the National Key Research and Development Program of
China (No. 2017YFD0200506) and the National Nature Science Foun-
dation of China (No. 21462012).
(E)‑1‑[4‑(Benzo[d]thiazol‑2‑yloxy)phenyl]‑3‑(3,4‑dimeth‑
ylphenyl)prop‑2‑en‑1‑one (2q, C24H19NO2S) White solid;
yield: 76%; m.p.: 123–125 °C; 1H NMR (400 MHz,
DMSO-d6): δ=8.31 (d, J=8.7 Hz, 2H, Ph-2, 6-H), 8.00 (d,
J=7.9 Hz, 1H, benzothiazole-4-H), 7.93 (d, J=15.6 Hz, 1H,
CO–C=CH), 7.73 (dd, J=12.0, 3.2 Hz, 3H, CO–CH, Ar(3,
4-di-CH3)-5, 6-H), 7.67 (d, J=8.7 Hz, 2H, Ph-3, 5-H), 7.62
(d, J=7.7 Hz, 1H, benzothiazole-7-H), 7.48–7.44 (m, 1H,
benzothiazole-5-H), 7.39–7.35 (m, 1H, benzothiazole-6-H),
7.24 (d, J=7.8 Hz, 1H, Ar(3, 4-di-CH3)-2-H), 2.29 (s, 3H,
CH3), 2.28 (s, 3H, CH3) ppm; 13C NMR (101 MHz, DMSO-
d6): δ = 188.33, 171.22, 157.93, 148.80, 145.08, 140.22,
137.39, 136.08, 132.71, 132.44, 131.29, 130.52, 130.26,
127.33, 127.10, 125.01, 122.85, 121.86, 121.36, 121.05,
19.97, 19.76 ppm; HRMS (ESI): m/z (calcd.) [M + H]+
386.1209, found 386.1203.
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