Synthesis and Cytotoxicity of Chalcone Based 1,2,3-Triazole Derivatives

Article abstract of DOI:10.1134/S1070363220040210

Abstract: Synthesis of a novel series of chalcone based 1,2,3-triazole derivatives and their anti-cancer studies are presented. Majority of the target compounds exhibit moderate to excellent activity against A-549 cells. Among the compounds screened 7c an

Full text of DOI:10.1134/S1070363220040210

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 4, pp. 697–702. © Pleiades Publishing, Ltd., 2020.
Synthesis and Cytotoxicity of Chalcone
Based 1,2,3-Triazole Derivatives
M. Raghavendera, A. Kishore Kumarb, V. Sunithaa, T. Vishnuc, and P. Jalapathia,*
a Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana, 500007 India
b Department of Humanities and Sciences, Vardhaman College of Engineering, Hyderabad, 501218 India
c Department of Sciences and Humanities, Matrusri Engineering College, Saidabad, Hyderabad, 500059 India
*e-mail: pochampalli.ou.chemi@gmail.com
Received January 11, 2020; revised March 17, 2020; accepted March 25, 2020
Abstract—Synthesis of a novel series of chalcone based 1,2,3-triazole derivatives and their anti-cancer studies are
presented. Majority of the target compounds exhibit moderate to excellent activity againstA-549 cells. Among the
compounds screened 7c and 7j demonstrate potent activity being compared with the standard drug Doxorubicin.
Keywords: chalcone, 1,2,3-triazole, anti-cancer, cytotoxicity
DOI: 10.1134/S1070363220040210
INTRODUCTION
hydrogen signal which was recorded in compound 2
spectrum. Condensation of acetylinic acetophenone 3 with
substituted benzaldehydes 4a, 4b under basic conditions
resulted in formation of the corresponding acetylinic
chalcones 5a, 5b in high yields. Disappearance of the
methyl group signals in 1H NMR spectra and new signals
in the aromatic region indicated formation of chalcones
5a, 5b. 1,3-Dipolar cycloaddition of acetylinic chalcones
5a, 5b to a variety of substituted azides 6a–6j gave the
targeted chalcone based 1,4-disubstituted 1,2,3-triazole
derivatives 7a–7j in excellent yields. Structures of all
the newly synthesized compounds were supported by IR,
NMR, and mass spectra.
Studied in depth various chalcone derivatives still
attract close attention due to their promising biological
activities including antiretroviral [1], anti-inflammatory
[2], antimicrobial [3], antihistaminic [4], antioxidant [5],
and many more. 1,2,3-Triazoles are used extensively as
structural components of a variety of bioactive molecules
characterized by antiviral [6], antimicrobial [7, 8],
antibacterial [9, 10], anti-inflammatory [11], antimalarial
[12] and antitubercular [13] activities. Some chalcone
based triazoles have been singled out as strong anticancer
agents [14–16].
The presented above information encouraged us to
combine chalcone and 1,2,3-triazole derivatives in the
molecules of pharmacological potential and test their
anticancer activity.
In vitro cytotoxicity studies against A549 cells.
The synthesized compounds 7a–7j were tested for their
anti-cancer activity using the MTT Cell viable assays
[17, 18] (Table 1). Eight compounds demonstrated the
moderate activity, whereas the products 7c and 7j were
characterized by potent cytotoxicity against A-549 cells.
The strong electron-withdrawing effect of F and Cl
substituents in the molecules could lead to their higher
polarizability, stronger binding of the molecules with
the receptor. According to the accumulated data, most of
the synthesized compounds exhibited anti-proliferative
activity against theA549 cancer cell lines (Table 2). This
was particularly true for compounds 7c and 7j, for which
reason their mechanism of action needs to be studied
closer.
RESULTS AND DISCUSSION
The target compounds 7a–7j were synthesized
by a four-step procedure (Scheme 1). The selective
O-alkylation of 1-(2,4-dihydroxyphenyl)ethanone (1)
was carried out upon refluxing it with propargyl bromide
and potassium carbonate affording para alkylated
1-[2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl]ethanone
(2) with 90% yield [7]. The intermediate 2 reacted with
ethyl bromide giving 1-[2-ethoxy-4-(prop-2-yn-1-yloxy)
phenyl]ethanone (3) (98% yield). Its formation was
confirmed by 1H NMR spectra that demonstrated typical
the ethyl group signals and disappearance of phenolic
697

698
RAGHAVENDER et al.
Scheme 1. Synthetic pathway to chalcone based 1,2,3-triazole derivatives 7a–7j.
Me
Br
O
OH
O
O
O
O
Br
O
K
CO
3, DMF
room temperature,
K
CO
2
3, acetone
2
HO
OH
reflux, 12 h, 90%
24 h, 98%
1
2
3
O
ethanol, KOH
4 h,
H
room temperature
R
4a, 4b
N
N
N
R1
RꢀN3
6aꢀ6i
R
R
O
O
O
O
O
.5H
CuSO4 2O
Sodium ascorbate
DMF+H
2O (1 : 1),
room temperature
O
ꢀ
7a 7l
5a, 5b
R = OMe (5a, 7a, 7b, 7c, 7d 7g 7h, 7i, 7j), R = H (5b, 7e, 7f); R1 = 3-(Me)Ph (7a), R1 = 4-(Me)Ph (7b),
4-(F)Ph (7c), R1 = 4-(NO2)Ph (7d); Ph (7e), 4-(F)Ph (7f), 3-(CH3CO)Ph (7g), C12H25 (7h), C14H29 (7i),
4-(Cl)Ph (7j).
[1-(2-Ethoxy-4-(prop-2-yn-1-yloxy)phenyl]-
ethanone (3). To an intensively stirred mixture of
compound 2 (3 g, 0.015 mol) with K2CO3 (4.3 g,
0.031 mol) in dry DMF, ethyl bromide (3.37 g,
0.031 mol) was added dropwise, and the mixture was
stirred for ca 24 h. Upon consumption of the starting
compound (TLC), crushed ice was added to the reaction
mixture. The precipitate so obtained was filtered off,
washed with water and diethyl ether to afford the pure
product 3. White solid, yield 93%. IR spectrum, ν, cm–1:
2365, 1643 (C=O). 1H NMR spectrum, δ, ppm: 1.46 t (J =
6.98 Hz, 3H), 2.54 d (J= 2.26 Hz, 1H), 2.56 s (3H), 4.11 q
(J = 6.96 Hz, 2H), 4.73 d (J= 2.3 Hz, 2H), 6.40–6.44
m (2H), 7.65 d. d (J= 7.07, 2.4 Hz,1H). MS: m/z: 219
[M + H]+.
EXPERIMENTAL
Commercially available reagents were used as
supplied, and all solvents were distilled before use.
All reactions were performed in oven-dried glassware.
Melting points were determined in open capillaries
and are uncorrected. IR spectra were recorded on a
Perkin−Elmer 337 grating IR spectrophotometer for solid
samples pelleted in KBr. NMR spectra were measured
on a BrukerAV-400 NMR spectrometer using DMSO-d6
as a solvent and TMS as an internal standard. ESI mass
spectra were measured on a QSTARXLhybrid MS system
(Applied Bio Systems) under electro spray ionization.
CHN analysis was carried out on a Perkin Elmer Model
2400 CHNS elemental analyzer. TLC was carried out on
Merck silica gel 60 F254 plates. The spots were visualized
under UV light at 254 nm or, alternatively, by staining
with aqueous basic potassium permanganate. Column
chromatography was carried out on a Merck silica gel
60A (100–200 mesh).
Synthesis of substituted chalcones 5a, 5b. To a
solution of acetylenic ketone (3) (0.004 mol) in EtOH
was added KOH (0.370 g, 0.0066). The mixtures was
stirred at room temperature for 20 min. A substituted
benzaldehyde 4a, 4b (0.004 mol) was added to the
mixture, and it was stirred for 8 h. Upon completion of the
process (TLC), ice-cold water was added to the mixture,
and it was neutralized by 0.1–0.2 N HCl till a precipitate
1-[2-Hydroxy-4-(prop-2-yn-1-yloxy)phenyl]-
ethanone (2) was synthesized according to the developed
earlier procedure [7].
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SYNTHESIS AND CYTOTOXICITY OF CHALCONE
Table 1. Cytotoxicity of chalcone based 1,2,3-triazole derivatives 7a–7j
699
Cell viability against A549 cells, %
μM
Compound
10
25
40
55
70
85
100
7a
89.77
92.39
81.25
92.58
92.69
89.77
90.58
91.26
75.28
83.41
87.22
72.69
85.51
83.58
85.22
83.41
85.69
61.38
77.22
83.69
62.58
81.06
78.47
80.05
77.22
71.59
50.58
69.89
79.33
55.36
7.33
61.04
77.99
48.22
76.01
75.11
74.4
58.69
71.44
39.61
70.09
64.29
69.97
63.57
43.95
16.86
57.28
69.36
22.47
65.98
61.08
65.22
55.47
31.29
8.69
7b
7c
7d
7e
77.25
77.29
72.58
63.42
32.47
7f
7g
7j
69.97
57.28
25.61
Doxorubicin
was formed. The precipitate was filtered off, washed with
water and cold MeOH to afford the corresponding pure
product 5a or 5b.
and ether to afford the corresponding pure white (unless
stated otherwise) solid compound 7a–7j.
(E)-1-(2-Ethoxy-4-{[1-(3-methylphenyl)-1H-1,2,3-
triazol-4-yl]methoxy}phenyl)-3-(4-methoxyphenyl)-
prop-2-en-1-one (7a). Yield 95%, mp 141–143°C. IR
(E)-1-[2-Ethoxy-4-(prop-2-yn-1-yloxy)phenyl]-3-
(4-methoxyphenyl)prop-2-en-1-one (5a). Light yellow
solid, yield 94%, mp 126–128°C. IR spectrum, ν, cm–1:
1
spectrum, ν, cm–1: 1655 (C=O). H NMR spectrum, δ,
1
ppm: 1.46 t (J = 6.91 Hz, 3H), 2.45 s (3H), 3.84 s (3H),
4.12 q (J = 6.87 Hz, 2H), 5.35 s (2H), 6.60–6.71 m
(2H), 6.91 d (J = 8.58 Hz, 2H), 7.41 t (J = 7.78 Hz, 1H),
7.45–7.70 m (7H), 7.78 d (J = 8.58 Hz, 1H), 8.06 s (1H).
13C NMR spectrum, δC, ppm: 14.8, 29.8, 55.5, 61.8,
64.5, 100.1, 106.6, 114.1, 118.8, 120.6, 121.4, 122.9,
125.5, 128.8, 129.2, 130.0, 131.0, 133.0, 136.0, 138.1,
142.2, 159.7, 161.4, 162.6, 190.6. MS: m/z: 470 [M +
H]+. Found, %: C 71.40; H 5.58; N 8.72. C28H27N3O4.
Calculated, %: C 71.62; H 5.80; N 8.95.
2360, 1658 (C=O). H NMR spectrum, δ, ppm: 1.47 t
(J = 6.96 Hz, 3H), 2.57 t (J = 2.38 Hz, 1H), 3.85 s (3H),
4.12 q (J = 6.96 Hz, 2H), 4.75 d (J = 2.38 Hz, 2H),
6.53–6.65 m (2H), 6.92 d (J = 8.77 Hz, 2H), 7.46–7.57 m
(3H), 7.65 d (J = 15.77 Hz, 1H), 7.78 d (J = 8.64 Hz,
1H). MS: m/z: 337 [M + H]+. Found, %: C 74.77; H 5.75.
C21H20O4. Calculated, %: C 74.98; H 5.99.
(E)-1-[2-Ethoxy-4-(prop-2-yn-1-yloxy)phenyl]-3-
phenylprop-2-en-1-one (5b). White solid, yield 98%, mp
113–115°C. IR spectrum, ν, cm–1: 2357, 1656 (C=O). 1H
NMR spectrum, δ, ppm: 1.46 t (J = 6.94 Hz, 3H), 2.58 t
(J = 2.36 Hz, 1H), 4.14 q (J = 6.98 Hz, 2H), 4.73 d
(J = 2.34 Hz, 2H), 6.54–6.67 m (2H), 6.95 d (J = 8.72 Hz,
2H), 7.45–7.60 m (4H), 7.67 d (J = 15.74 Hz, 1H), 7.74 d
(J = 8.68 Hz, 1H). MS: m/z: 307 [M + H]+. Found, %: C
78.23; H 5.75. C21H20O4. Calculated, %: C 78.41; H 5.92.
Table 2. IC50 values of chalcone based 1,2,3-triazoles against
A549 cells
Compound
IC50+SD, μM
109.19±1.25
174.27±1.35
62.51±0.85
158.49±1.13
135.04±1.33
159.87±0.98
119.15±1.19
75.41±1.05
39.86±1.15
7a
7b
Synthesis of chalcone based 1,4-disubstituted
1,2,3-triazole derivatives (7a–7j). A compound 5a or
5b (100 mg, 1 eq) was dissolved in 5 mL of aqueous
DMF (50%) and mixed with CuSO4.5H2O (5 mol %),
sodium ascorbate (10 mol %) and one of azides 6a–6i
(1.5 eq). The reaction mixture was stirred for 1 h at room
temperature. Upon completion of the process (TLC)
the reaction mixture was poured over crushed ice, solid
precipitate was filtered off, washed with excess of water
7c
7d
7e
7f
7g
7j
Doxorubicin
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RAGHAVENDER et al.
(E)-1-(2-Ethoxy-4-{[1-(4-methylphenyl)-1H-1,2,3-
triazol-4-yl]methoxy}phenyl)-3-(4-methoxyphenyl)-
NMR spectrum, δC, ppm: 15.0, 55.5, 63.3, 65.1, 100.5,
107.7, 117.4, 119.1, 122.1, 122.9, 123.2, 127.1, 128.4,
129.7, 129.7, 133.2, 136.4, 141.1, 158.7, 162.1, 163.6,
164.7, 190.7. MS: m/z: 456 [M + H]+. Found, %: C 70.96;
H 5.30; N 9.01. C27H25N3O4. Calculated, %: C 71.19; H
5.53; N 9.22.
prop-2-en-1-one (7b). Yield 96%, mp 122–124°C. IR
1
spectrum, ν, cm–1: 1651 (C=O). H NMR spectrum,
δ, ppm: 1.47 t (J = 6.95 Hz, 3H), 2.43 s (3H), 3.85 s
(3H), 4.13 q (J = 6.95 Hz, 2H), 5.35 s (2H), 6.60–6.71
m (2H), 6.91 d (J = 8.75 Hz, 2H), 7.33 d (J = 8.21 Hz,
2H), 7.47–7.57 m (3H), 7.59–7.68 m (3H), 7.79 d (J =
8.60 Hz, 1H), 8.04 s (1H). 13C NMR spectrum, δC, ppm:
14.9, 29.8, 55.4, 61.8, 64.5, 100.1, 106.4, 114.5, 116.3,
116.8, 122.5, 123.0, 123.3, 124.9, 129.0, 129.6, 133.1,
142.0, 158.9, 160.9, 161.8, 162.7, 163.9, 190.6. MS:
m/z: 470 [M + H]+. Found, %: C 71.40; H 5.58; N 8.72.
C28H27N3O4. Calculated, %: C 71.62; H 5.80; N 8.95.
(E)-1-(2-Ethoxy-4-{[1-(4-fluorophenyl)-1H-1,2,3-
triazol-4-yl]methoxy}phenyl)-3-phenylprop-2-en-1-
one (7f). Yield 85%, mp 117–119°C. IR spectrum, ν,
1
cm–1: 1651 (C=O). H NMR spectrum, δ, ppm: 1.47 t
(J = 6.34 Hz, 3H), 4.13 q (J = 6.91 Hz, 2H), 5.35 s (2H),
6.58–6.74 m (2H), 7.23 d (J = 7.76 Hz, 2H), 7.38 s (3H),
7.56–7.84 m (7H), 7.99–8.17 m (1H). 13C NMR spectrum,
δC, ppm: 14.8, 62.1, 64.4, 100.0, 106.3, 116.7, 117.0,
122.6, 122.7, 122.8, 127.3, 128.2, 128.9, 129.9, 133.0,
135.5, 141.7, 159.9, 161.3, 162.6, 163.8, 190.4. MS:
m/z: 444 [M + H]+. Found, %: C 70.20; H 4.77; N 9.22.
C26H22FN3O4. Calculated, %: C 70.42; H 5.00; N 9.48.
(E)-1-(2-Ethoxy-4-{[1-(4-fluorophenyl)-1H-1,2,3-
triazol-4-yl]methoxy}phenyl)-3-(4-methoxyphenyl)-
prop-2-en-1-one (7c). Yield 82%, mp 129–131°C. IR
1
spectrum, ν, cm–1: 1653 (C=O). H NMR spectrum, δ,
ppm: 1.47 t (J = 6.90 Hz, 3H), 3.85 s (3H), 4.13 q (J =
6.86 Hz, 2H), 5.36 s (2H), 6.59–6.73 m (2H), 6.92 d (J =
8.55 Hz, 2H), 7.19–7.26 m (2H), 7.47–7.82 m (7H), 8.03 s
(1H). 13C NMR spectrum, δC, ppm: 14.8, 55.3, 61.9, 64.3,
100.0, 106.2, 114.3, 116.7, 116.9, 122.6, 122.7, 123.0,
125.1, 128.2, 129.8, 132.8, 141.7, 159.7, 161.2, 161.3,
162.3, 163.8, 190.4. MS: m/z: 474 [M + H]+. Found, %:
C 68.23; H 4.89; N 8.64. C27H24FN3O4. Calculated, %:
C 68.49; H 5.11; N 8.87.
(E)-1-(4-{[1-(3-Acetylphenyl)-1H-1,2,3-triazol-4-
yl]methoxy}-2-ethoxyphenyl)-3-(4-methoxyphenyl)-
prop-2-en-1-one (7g). Light yellow solid, yield 95%,
mp 135–137°C. IR spectrum, ν, cm–1: 1705 (C=O), 1658
(C=O). 1H NMR spectrum, δ, ppm: 1.47 t (J = 6.92 Hz,
3H), 2.69 s (3H), 3.85 s (3H), 4.14 q (J = 6.89 Hz, 2H),
5.37 s (2H), 6.61–6.72 m (2H), 6.92 d (J = 8.64 Hz, 2H),
7.46–7.57 m (3H), 7.62–7.70 m (2H), 7.79 d (J = 8.57 Hz,
1H), 8.04 d (J = 7.86 Hz, 2H), 8.18 s (1H), 8.30 s (1H).
13C NMR spectrum, δC, ppm: 14.9, 29.8, 55.3, 61.8, 64.5,
101.1, 105.9, 115.1, 118.8, 120.5, 122.3, 123.5, 126.0,
128.1, 129.0, 129.5, 132.5, 133.7, 136.9, 138.6, 142.9,
159.6, 161.0, 163.2, 190.7, 195.2. MS: m/z: 498 [M +
H]+. Found, %: C 69.79; H 5.22; N 8.21. C29H27N3O5.
Calculated, %: C 70.01; H 5.47; N 8.45.
(E)-1-(2-Ethoxy-4-{[1-(4-nitrophenyl)-1H-1,2,3-
triazol-4-yl]methoxy}phenyl)-3-(4-methoxyphenyl)-
prop-2-en-1-one (7d). Yellow solid, yield 90%, mp
167–169°C. IR spectrum, ν, cm–1: 1659 (C=O). 1H NMR
spectrum, δ, ppm: 1.37 t (J = 6.77 Hz, 3H), 3.81 s (3H),
4.19 q (J = 6.90 Hz, 2H), 5.39 s (2H), 6.74–6.87 m (2H),
7.01 d (J = 8.46 Hz, 2H), 7.52 s (2H), 7.61–7.72 m (3H),
8.26 d (J = 8.86 Hz, 2H), 8.48 d (J = 8.91 Hz, 2H), 9.22 s
(1H). 13C NMR spectrum, δC, ppm: 14.8, 55.5, 61.8, 64.5,
100.4, 107.2, 115.3, 116.8, 117.8, 122.6, 123.6, 124.5,
127.2, 130.2, 132.7, 136.8, 143.5, 159.5, 161.1, 162.7,
162.8, 163.9, 190.5. MS: m/z: 501 [M + H]+. Found, %:
C 64.55; H 4.83; N 10.96. C27H24N4O6. Calculated, %:
C 64.79; H 4.83; N 11.19.
(E)-1-{4-[(1-Dodecyl-1H-1,2,3-triazol-4-yl)
methoxy]-2-ethoxyphenyl}-3-(4-methoxyphenyl)-
prop-2-en-1-one (7h). Yield 98%, mp 132-134°C. IR
1
spectrum, ν, cm–1: 1661 (C=O). H NMR spectrum, δ,
ppm: 0.87 d (J = 6.18 Hz, 3H), 1.20–1.35 m (18H), 1.46 t
(J = 6.51 Hz, 3H), 1.92 s (2H), 3.85 s (3H), 4.11 d (J =
6.59 Hz, 2H), 4.36 s (2H), 5.27 s (2H), 6.60 s (2H), 6.91 d
(J = 8.06 Hz, 2H), 7.54 d (J = 8.09 Hz, 3H), 7.63 s (2H),
7.73–7.81 m (1H). 13C NMR spectrum, δC, ppm: 14.1,
14.8, 22.6, 26.4, 28.9, 29.3, 29.5, 30.2, 31.8, 50.6, 55.3,
62.2, 64.3, 100.0, 106.3, 114.3, 122.8, 125.1, 128.2, 129.8,
132.7, 141.6, 159.7, 161.1, 162.5, 190.5. MS: m/z: 548
[M+ H]+. Found, %: C 72.13; H 8.04; N 7.44. C33H45N3O4.
Calculated, %: C 72.36; H 8.28; N 7.67.
(E)-1-{2-Ethoxy-4-[(1-phenyl-1H-1,2,3-triazol-4-
yl)methoxy]phenyl}-3-(4-methoxyphenyl)prop-2-en-
1-one (7e). Yield 95%, mp 108–110°C. IR spectrum, ν,
1
cm–1: 1661 (C=O). H NMR spectrum, δ, ppm: 1.47 t
(J = 6.90 Hz, 4H), 3.85 s (3H), 4.13 q (J = 6.84 Hz, 2H),
5.36 s (2H), 6.61–6.72 m (2H), 6.92 d (J = 8.53 Hz, 2H),
7.43–7.59 m (6H), 7.61–7.82 m (5H), 8.08 s (1H). 13C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 4 2020

SYNTHESIS AND CYTOTOXICITY OF CHALCONE
701
(E)-1-{2-Ethoxy-4-[(1-tetradecyl-1H-1,2,3-triazol-
4-yl)methoxy]phenyl}-3-(4-methoxyphenyl)prop-2-
en-1-one (7i). Yield 94%, mp 143–145°C. IR spectrum,
ν, cm–1: 1660 (C=O). 1H NMR spectrum, δ, ppm: 0.88 s
(3H), 1.19–1.50 m (29H), 1.91 s (2H), 3.84 s (3H), 4.11 d
(J = 2.10 Hz, 2H), 4.36 s (2H), 5.27 s (2H), 6.60 s (2H),
6.91 d (J = 3.33 Hz, 2H), 7.57 d (J = 31.87 Hz, 6H). 13C
NMR spectrum, δC, ppm: 14.1, 14.8, 22.6, 26.4, 28.9,
29.2, 29.3, 29.5, 29.6, 29.8, 30.2, 31.9, 50.5, 55.3, 62.1,
64.3, 100.0, 106.3, 114.3, 122.7, 122.8, 125.1, 128.2,
129.8, 132.7, 141.6, 159.7, 161.1, 162.5, 190.4. MS:
m/z: 604 [M + H]+. Found, %: C 73.27; H 8.62; N 6.73.
C37H53N3O4. Calculated, %: C 73.60; H 8.85; N 6.96.
via the Huisgen 1,3-dipolar cycloaddition reaction in high
yields and characterized by IR, NMR and mass spectra.
The synthesized target compounds demonstrate moderate
to excellent anti-cancer activity.According to cytotoxicity
tests, the compounds 7c and 7j are characterized by potent
cytotoxicity againstA549 cells compared to the standard
drug Doxorubicin.
ACKNOWLEDGMENTS
M. Raghavender thanks the Head of the Department,
Osmania University, Hyderabad, India and Central Facilities for
Research and Development, Osmania University, Hyderabad,
India for providing analytical support.
CONFLICT OF INTEREST
(E)-1-(4-{[1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-
yl]methoxy}-2-ethoxyphenyl)-3-(4-methoxyphenyl)-
prop-2-en-1-one (7j). Yield 92%, mp 115–117°C. IR
No conflict of interest was declared by the authors.
1
spectrum, ν, cm–1: 1658 (C=O). H NMR spectrum, δ,
REFERENCES
ppm: 1.47 t (J = 6.95 Hz, 3H), 3.84 s (3H), 4.12 q (J =
6.96 Hz, 2H), 5.35 s (2H), 6.60–6.70 m (2H), 6.91 d (J =
8.76 Hz, 2H), 7.41–7.57 m (5H), 7.61–7.69 m (2H),
7.79 d. d (J = 8.59, 5.30 Hz, 2H), 8.08 d (J = 5.27 Hz,
1H). 13C NMR spectrum, δC, ppm: 14.8, 55.4, 61.9,
64.4, 100.0, 106.2, 114.3, 118.6, 120.9, 121.0, 123.1,
125.1, 128.2, 129.1, 129.9, 130.9, 132.9, 135.7, 137.7,
141.8, 159.8, 161.2, 162.3, 190.5. MS: m/z: 490 [M +
H]+. Found: C 65.96; H 4.72; N 8.36. C27H24ClN3O4.
Calculated, %: C 66.19; H 4.94; N 8.58.
1. Mahapatra, D. K., Asati, V., and Bharti, S.K., Eur. J.
Med. Chem., 2015, vol. 92, p. 839.
https://doi.org/10.1016/j.ejmech.2015.01.051
2. Chen, M., Christensen, S.B., Zhai, L., Rasmussen, M.,
Theander, T., Frøkjaer, S., Steffansen, B., Davidsen, J.,
and Kharazmi, A., J. Infect. Dis., 1997, vol. 176, no. 5,
p. 1327.
https://doi.org/10.1086/514129
3. Sunitha, V., Kumar, A.K., Mahesh, M., Shankaraiah, P.,
Jalapathi, P., and Lincoln, C.A., Russ. J. Gen. Chem.,
2018, vol. 88, no. 9, p. 1904-1911.
In vitro cytotoxicity studies (MTT assay). The tested
samples were dissolved in DMSO and a maintenance
medium to get an individual stock solution of 1 mg/mL.
The cytotoxicity assays were carried out on 96 well
microtitre plates containing 10 000 cells/well. Media
containing different concentrations of the test compounds
were added after 24 h of partial monolayer cell formation.
Control cells were incubated in culture medium without
test compounds. The microtitre plates were incubated at
37°C in a humidified incubator with 5% CO2 for 72 h.
Then 20 μLof MTT solution (2mg/ml in PBS) was added
to the plates, and those were further incubated for 4 h at
37°C. MTT-formazan crystals formed were dissolved in
100 μL of DMSO and optical density was read with a
microtitre plate reader (Biorad) at 570 nm. The percentage
cytotoxicity of each compound at various concentrations
was calculated, and IC50 was determined [17, 18].
https://doi.org/10.1134/S1070363218090232
4. Kantevari, S., Addla, D., Bagul, P.K., Sridhar, B.,
and Banerjee, S.K., Bioorg. Med. Chem., 2011, vol. 19,
no. 16, p. 4772.
https://doi.org/10.1016/j.bmc.2011.06.085
5. Mishra, L., Itokawa, H., Bastow, K.F., Tachibana, Y.,
Nakanishi, Y., Kilgore, N., Lee, K.-H., and Sinha, R.,
Bioorg. Med. Chem., 2001, vol. 9, no. 7, p. 1667.
https://doi.org/10.1016/S0968-0896(01)00074-8
6. Das, K., Bauman, J.D., Rim, A.S., Dharia, C.,
Clark, Jr.A.D., Camarasa, M.-J., Balzarini, J., and
Arnold, E., J. Med. Chem., 2011, vol. 54, no. 8,
p. 2727.
https://doi.org/10.1021/jm101536x
7. Sunitha, V., Kumar, A.K., Shankar, B., Kumar, A.A.,
Krishna, T., Lincoln, C.A., and Pochampalli, J., Russ. J.
Gen. Chem., 2017, vol. 87, no. 2, p. 322.
https://doi.org/10.1134/S1070363217020281
CONCLUSIONS
8. Kumar, A.K., Sunitha, V., Shankar, B., Krishna, T.M.,
Lincoln, C.A., and Jalapathi, P., Russ. J. Gen. Chem.,
2017, vol. 87, no. 9, p. 2011.
A new series of chalcone based 1,4-disubstituted
1,2,3-triazole derivatives (7a–7j) has been synthesized
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 4 2020

702
RAGHAVENDER et al.
https://doi.org/10.1134/S1070363217090171
14. Yadav, P., Lal, K., Kumar, A., Guru, S.K., Jaglan, S., and
Bhushan, S., Eur. J. Med. Chem., 2017, vol. 126, p. 944.
https://doi.org/10.1016/j.ejmech.2016.11.030
9. Sunitha, V., Kumar, A. K., Shankaraiah, P., Jalapathi, P.,
and Lincoln, C.A., Russ. J. Gen. Chem., 2018, vol. 88,
no. 7, p. 1515.
15. Parveen, Z., Brunhofer, G., Jabeen, I., Erker, T.,
Chiba, P., and Ecker, G.F., Bioorg. Med. Chem., 2014, vol. 22,
no. 7, p. 2311.
https://doi.org/10.1134/S1070363218070265
10. Kumar, A.K., Sunitha, V., Shankaraiah, P., Siddhartha, M.,
and Jalapathi, P., Russ. J. Gen. Chem., 2018, vol. 88,
no. 4, p. 789.
https://doi.org/10.1016/j.bmc.2014.02.005
16. Hans, R.H., Guantai, E.M., Lategan, C., Smith, P.J., Wan, B.,
Franzblau, S.G., Gut, J., Rosenthal, P.J., and Chibale, K.,
Bioorg. Med. Chem. Lett, 2010, vol. 20, no. 3, p. 942.
https://doi.org/10.1016/j.bmcl.2009.12.062
https://doi.org/10.1134/S1070363218040254
11. Kumar, A.K., Sunitha, V., Shankar, B., Ramesh, M.,
Krishna, T.M., and Jalapathi, P., Russ. J. Gen. Chem.,
2016, vol. 86, no. 5, p. 1154.
https://doi.org/10.1134/S1070363216050297
12. Kumar, K., Pradines, B., Madamet, M., Amalvict, R., and
Kumar, V., Eur. J. Med. Chem., 2014, vol. 86, p. 113.
https://doi.org/10.1016/j.ejmech.2014.08.053
13. Patpi, S. R., Pulipati, L., Yogeeswari, P., Sriram, D., Jain, N.,
Sridhar, B., Murthy, R., Kalivendi, S.V. and Kanteva-
ri, S., J. Med. Chem., 2012, vol. 55, no. 8, p. 3911.
https://doi.org/10.1021/jm300125e
17. Kant, R., Kumar, D., Agarwal, D., Gupta, R.D.,
Tilak, R., Awasthi, S.K., and Agarwal, A., Eur. J. Med.
Chem., 2016, vol. 113, p. 34.
https://doi.org/10.1016/j.ejmech.2016.02.041
18. Dalla Via, L., Gia, O., Chiarelotto, G., and Ferlin, M.G.,
Eur. J. Med. Chem., 2009, vol. 44, no. 7, p. 2854.
https://doi.org/10.1016/j.ejmech.2008.12.011
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