Synthesis and biological evaluation of chalcone-triazole hybrid derivatives as 15-LOX inhibitors

Article abstract of DOI:10.1515/znb-2017-0115

An efficient aldol condensation/click reaction sequence is employed for the synthesis of chalcone-triazole-based derivatives in moderate to good yields. The ability of target compounds to inhibit 15-lipoxygenase enzyme was investigated and moderate to low inhibitory activities were observed for the synthesized compounds.

Full text of DOI:10.1515/znb-2017-0115

Z. Naturforsch. 2018; 73(2)b: 77–83
Ali Asadipour, Saeedeh Noushini, Setareh Moghimi, Mohammad Mahdavi, Hamid Nadri,
ASliyrenzatMhoreadsi,iSshaabnnamdShbaiboanli,oLogghimcaanlFierovozapoluur aantdiAolirneza Foroumadi*
of chalcone-triazole hybrid derivatives as
15-LOX inhibitors
https://doi.org/10.1515/znb-2017-0115
non-heme iron [5]. There are three major isoforms of LOX
in human body: 5-LOX, 12-LOX and 15-LOX. The numbers
clearly show the positional specificity for oxygenation of
polyunsaturated fatty acid, arachidonic acid (AA). The
catalytic oxidation of the key substrate, AA, necessarily
needs the conversion of the inactive form of the enzyme
(Fe3+) to the active form, ferric ion (Fe2+) [6]. The products
of this catalytic process (eicosanoids) result in inflam-
matory mediators (lipoxins and leukotrienes), which are
involved in etiology of certain disease such as cardiovas-
cular diseases, cancer, asthma, psoriasis and rheuma-
toid arthritis [7–9]. The ability of heterocyclic systems
in preventing the single-electron transfer between Fe3+
and Fe2+, consequently led to the activation of enzyme,
has been widely considered in the literature as a signifi-
cant mechanism for LOX inhibition [10]. Regarding the
correlation between LOXs and inflammatory reactions,
the inhibition of LOX by heterocyclic systems could be
regarded as a treatment strategy of inflammatory and
allergic diseases.
Chalcone (PhCOCH=CHPh) is a privileged frame-
work in medicinal chemistry regarding the broad spec-
trum of pharmacological properties associated with this
compound and its derivatives [11]. Meanwhile, hydroxy-
lated chalcones manifest multiple prominent bioac-
tivities [12–17] and are also the main precursor for the
construction of biflavonoids [16, 17]. In this context, the
excellent in vitro and in vivo anti-inflammatory activities
of 2-hydroxy chalcones and flavones were presented by
Alcaraz et al. in 1995 [18], which inspired us to design
our project for the synthesis of novel chalcone-contain-
ing compounds.
Received June 25, 2017; accepted October 15, 2017
Abstract: An efficient aldol condensation/click reaction
sequence is employed for the synthesis of chalcone-
triazole-based derivatives in moderate to good yields.
The ability of target compounds to inhibit 15-lipoxy-
genase enzyme was investigated and moderate to low
inhibitory activities were observed for the synthesized
compounds.
Keywords: chalcone; lipoxygenase; quercetine; triazole.
1 Introduction
Lipoxygenases (LOXs) are a heterogeneous family of non-
heme, iron-oxidizing enzymes in animal and vegetal
kingdoms, converting fatty acids and esters into their
hydroperoxy analogs [1–4]. LOX proteins consist of a
single polypeptide chain with two domains, including
N-terminal domain and a large catalytic domain with
*Corresponding author: Alireza Foroumadi, Department of Medicinal
Chemistry, Faculty of Pharmacy, Tehran University of Medical
Sciences, Tehran, I.R. Iran; and Department of Medicinal Chemistry,
Faculty of Pharmacy and Neuroscience Research Center, Institute
of Neuropharmacology, Kerman University of Medical Sciences,
Kerman, I.R. Iran, e-mail: aforoumadi@yahoo.com
Ali Asadipour: Department of Medicinal Chemistry, Faculty
of Pharmacy and Neuroscience Research Center, Institute of
Neuropharmacology, Kerman University of Medical Sciences,
Kerman, I.R. Iran
1,2,3-Triazole is an important heteroaromatic nucleus
in pharmacological agents [19]. Relied on this fact, tria-
zole is introduced as an indispensable anchor for the
design and synthesis of novel therapeutic agents [20–24].
The potential of triazole-based compounds is that they
have been reported in the literature as anti-inflammatory
agents [25–27], because of their satisfactory binding affin-
ity to the target enzyme [28–31]. The copper-catalyzed
Saeedeh Noushini, Setareh Moghimi, Shabnam Shabani and
Loghman Firoozpour: Drug Design and Development Research
Center, Tehran University of Medical Sciences, Tehran, I.R. Iran
Mohammad Mahdavi: Endocrinology and Metabolism Research
Center, Endocrinology and Metabolism Clinical Sciences Institute,
Tehran University of Medical Sciences, Tehran, I.R. Iran
Hamid Nadri and Alireza Moradi: Department of Medicinal
Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of
Medical Sciences, Yazd, I.R. Iran
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78ꢀ ꢀA. Asadipour et al.: Synthesis and biological evaluation of chalcone-triazole hybrid derivatives
azide-alkyne cycloaddition reaction (CuAAC) [32–34] has association with potential pharmaceutical values of tria-
manifested itself as a nearly perfect and convenient tool to zoles [35] will highlight the potential worth of our target
build triazole skeleton. An efficient preparation method in compounds. This ambience along with our expertise in
O
OHC
OHC
a
b
c
OH
O
O
OH
R1
R1
R1
1
2
3
O
O
OH
N
R1
4
N
N
R2
Scheme 1:ꢀ(a) Propargyl bromide, DMF, K2CO3, 80°C; (b) 2-hydroxy acetophenone, NaOH, EtOH, r.t., then HCl; (c) benzyl halides, NaN3, CuI,
t-BuOH-H2O, r.t.
O
O
O
N
N
N
OH
N
N
N
HO
HO
N
N
O
N
O
O
O
N+
O−
Cl
O
4c (65%)
20.7%
4b (68%)
18.8%
4a (76%)a
32.1%b
OH
OH
OH
Cl
N
N
N
O
N
N
O
O
N
N
N
O
O
O
N
4d (65%)
20.8%
4f (74%)
26.8%
4e (72%)
30.5%
OH
OH
OH
O
N
N
N
O
N
N
O
N
O
N
N
O
O
O
N
O
O
O
4h (71%)
16.1%
4g (63%)
25.3%
4i (75%)
23.8%
OH
OH
OH
N
N
Cl
Cl
Cl
O
N
N
O
N
O
N
N
N
O
O
O
N
O
O
Cl
O
4l (73%)
40.3%
4k (67%)
35.1%
4j (61%)
12.2%
Scheme 2:ꢀEffect of the synthesized compounds on 15-LOX activity (Scheme 1). aIsolated yields; b15-lipoxygenase inhibitory activity (%)
at 8 μm.
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ꢂ79
this field [36–40] motivated us to introduce new mole- to higher activity in comparison to 4-nitro and 4-chloro
cules containing mentioned moieties, meaning triazole analogs.
and chalcone, into final compounds and evaluate their
15-LOX inhibitory activities.
3 Conclusion
2 Results and discussion
To conclude, a new series of chalcone-triazole system
has been synthesized and evaluated as soybean 15-LOX
inhibitors. These new hybrids exhibited moderate to
low inhibitory activities. Among the synthesized com-
pounds, 4l exhibited the greatest 15-LOX inhibitory
activity. These results showed that this compound
should undergo further optimization in the field of
15-LOX inhibitors.
2.1 Chemistry
The synthesis of title compounds is outlined in Scheme 1.
First of all, the propargylated products were obtained
by reacting 2- and 4-hydroxybenzaldehyde derivatives
with propargyl bromide in DMF at 80°C. After inserting
external alkyne moiety, the next step was carried out
by condensing 2-hydroxy acetophenone and 2a–2c in
basic ethanol solution. Upon acidification and recrystal-
lization from ethanol, the key intermediate 3 underwent
CuAAC to yield the desired compounds 4a–4l. To install
4 Experimental section
triazole ring, benzyl azides were synthesized from the 4.1 15-LOX inhibition assay
corresponding benzyl halide and sodium azide by stir-
ring in H2O-t-BuOH. Upon the addition of this mixture To evaluate 15-LOX (Lipoxidase from Glycine max,
to the stirring solution of compounds 3a–3c and the soybean) inhibitory activity of new synthesized com-
catalytic amounts of copper iodide, the triazole ring was pounds, the stock solution of the compounds were pre-
constructed.
pared by dissolving them in 1 mL of dimethyl sulfoxide
To probe the reaction generality, different benzal- (DMSO). To prepare substrate solution (stock concentra-
dehydes and benzyl halides were examined, which suc- tionꢀ=ꢀ38 mM) 12 μL linoleic acid was dissolved in 988 μL
cessfully afforded chalcone-triazole-based systems in ethanol. This solution should be used the same day it is
good yields. The structures and yields are summarized in made. The final concentration of the substrate will be 122
Scheme 2.
μM. Five different concentrations of each compound were
tested in triplicate to obtain the inhibition range between
20% and 80%. The test solution was a mixture of 3 mL
phosphate buffer (0.1 m, pHꢀ=ꢀ8), 50 μL enzyme solution
(final concentration: 167 u mL−1) and 50 μL of target com-
pound solution. Being incubated for 4 min, the substrate
(linoleic acid, final concentration: 122 μM) was added
and the change in absorbance was measured for 60 s
at 234 nm. A control test was performed with the same
volume of DMSO (50 μL) to eliminate the effect of DMSO
on enzyme activity.
2.2 Pharmacology
2.2.1 15-LOX inhibitory activity
The inhibitory effects of the synthesized compounds
are determined and listed in Scheme 2. All of the syn-
thesized compounds exhibited weak inhibitory activi-
ties compared to the reference drug, quercetine. In
general, compounds 4a, 4e, 4k and 4l revealed good
inhibitory activities against 15-LOX. The highest activ-
ity was observed in compound 4l, possessing two 4.2 Procedure for the synthesis
chlorine atoms. The presence of chlorine at para posi-
of compounds 2a–2c
tion is responsible for this significant activity. It seems
that increasing the size of substituents, from methyl to The appropriate hydroxyl benzaldehydes (20 mmol)
methoxy group, led to the decreased activities. In com- and K2CO3 (20 mmol) were dissolved in DMF (35 mL)
pounds 4a–4c, derived from salicylaldehyde, the pres- and stirred for 1 h at room temperature. Then, propar-
ence of a strong electron-donating group, methoxy, led gyl bromide (20 mmol) was added and the mixture was
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80ꢀ ꢀA. Asadipour et al.: Synthesis and biological evaluation of chalcone-triazole hybrid derivatives
heated to 80°C. After completion of the reaction, the 163.5, 194.3 ppm. – Anal. for C26H23N3O4: Calcd. C 70.73, H
mixture was poured into an ice–water mixture and the 5.25, N 9.52; found C 70.48, H 5.41, N 9.79.
product was appeared as a white yellowish precipitate,
separated and washed with cold water to afford the pro-
pargylated products.
4.4.2 (E)-3-(2-((1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)
methoxy)phenyl)-1-(2-hydroxyphenyl)prop-2-en-
1-one (4b)
4.3 Procedure for the synthesis
of compounds 3a–3c
Yield: 0.30 g (68%); m.p. 181–183°C. – IR (KBr, cm−1):
νꢀ=ꢀ3420, 3119, 1680, 1641, 1506, 1233. – 1H NMR (500 MHz,
To a solution of 2-hydroxyacetophenone (5 mmol) and 2a– CDCl3, 25°C, TMS): δꢀ=ꢀ5.33 (s, 2H), 5.52 (s, 2H), 6.91 (t,
2c (5 mmol) in ethanol (50 mL), the aqueous solution of Jꢀ=ꢀ7.5 Hz, 1H), 7.03–7.07 (m, 2H), 7.13 (d, Jꢀ=ꢀ8.5 Hz, 1H), 7.20
NaOH (25 mL, 50%) was added and the reaction was con- (d, Jꢀ=ꢀ8.2 Hz, 2H), 7.34 (d, Jꢀ=ꢀ8.2 Hz, 2H), 7.41 (t, Jꢀ=ꢀ7.4 Hz,
tinued at room temperature. Upon completion, indicated 1H), 7.50 (t, Jꢀ=ꢀ7.5 Hz, 1H), 7.61 (s, 1H), 7.64 (d, Jꢀ=ꢀ7.6 Hz,
by thin-layer chromatography, the reaction mixture was 1H), 7.79–7.82 (m, 1H), 7.83 (d, Jꢀ=ꢀ15.5 Hz, 1H), 8.14 (d,
diluted and acidified to pHꢀ=ꢀ9 with HCl (10%). The result- Jꢀ=ꢀ15.5 Hz, 1H), 12.91 (s, 1H) ppm. – 13C NMR (125 MHz,
ing suspension was extracted with ethyl acetate, washed CDCl3, 25°C, TMS): δꢀ=ꢀ53.3, 62.4, 112.8, 118.4, 121.3, 121.5,
with brine, dried and concentrated in vacuo. The result- 122.9, 123.9, 126.6, 126.9, 127.0, 127.7, 129.4, 130.0, 132.1, 132.7,
ant yellow oil was recrystallized from ethanol to afford the 134.9, 136.2, 140.8, 144.1, 157.6, 163.5, 194.2 ppm. – Anal. for
desired products.
C25H20ClN3O3: Calcd. C 67.34, H 4.52, N 9.42; found C 67.60,
H 4.37, N 9.27.
4.4 Procedure for the synthesis
of compounds 4a–4l
4.4.3 (E)-3-(2-((1-(4-Nitrobenzyl)-1H-1,2,3-triazol-4-yl)
methoxy)phenyl)-1-(2-hydroxyphenyl)prop-2-en-
1-one (4c)
The different benzyl halides (1.1 mmol), sodium azide
(0.9 mmol) and triethylamine (1.3 mmol) were stirred in
water:tert-butanol (1:1, 10 mL) for 1 h at room temperature. Yield: 0.30 g (65%); m.p. 174–176°C. – IR (KBr, cm−1):
This solution was added to the mixture of 3a–3c (1 mmol) νꢀ=ꢀ3446, 3085, 1635, 1559, 1517, 1383. – 1H NMR (500 MHz,
and CuI (10 mol%). This mixture was stirred at room CDCl3, 25°C, TMS): δꢀ=ꢀ5.27 (s, 2H), 5.67 (s, 2H), 6.91 (t,
temperature for another 24 h. The reaction mixture was Jꢀ=ꢀ7.5 Hz, 1H), 7.01–7.13 (m, 2H), 7.35 (d, Jꢀ=ꢀ7.7 Hz, 1H),
extracted with ethyl acetate, dried and purified by column 7.50–7.52 (m, 1H), 7.65 (d, Jꢀ=ꢀ7.8 Hz, 2H), 7.71 (s, 1H), 7.78 (d,
chromatography (30% ethyl acetate-petroleum ether to Jꢀ=ꢀ15.5 Hz, 1H), 7.83 (d, Jꢀ=ꢀ7.8 Hz, 1H), 7.92 (d, Jꢀ=ꢀ7.8 Hz, 2H),
50% ethyl acetate-petroleum ether).
8.15–8.23 (m, 3H), 12.86 (s, 1H) ppm. – 13C NMR (125 MHz,
CDCl3, 25°C, TMS): δꢀ=ꢀ53.2, 62.3, 118.8, 121.2, 121.5, 121.7,
122.6, 123.1, 124.3, 126.6, 127.0, 127.7, 128.6, 129.5, 129.7, 132.2,
136.1, 136.3, 140.7, 144.8, 148.1, 154.3, 192.5 ppm. – Anal. for
C25H20N4O5: Calcd. C 65.78, H 4.42, N 12.27; found C 65.59, H
4.26, N 12.40.
4.4.1 (E)-1-(2-Hydroxyphenyl)-3-(2-((1-(4-
methoxybenzyl)-1H-1,2,3-triazol-4-yl)methoxy)
phenyl)prop-2-en-1-one (4a)
Yield: 0.33 g (76%); m.p. 133–135°C. – IR (KBr, cm−1):
1
νꢀ=ꢀ3415, 3126, 1687, 1636, 1516, 1250, 1052. – H NMR 4.4.4 (E)-3-(4-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)
(500 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ3.81 (s, 3H), 5.31 (s, 2H),
5.50 (s, 2H), 6.87 (d, Jꢀ=ꢀ8.5 Hz, 2H), 6.91 (t, Jꢀ=ꢀ6.80 Hz, 1H),
phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (4d)
7.02–7.05 (m, 2H), 7.12 (d, Jꢀ=ꢀ7.7 Hz, 1H), 7.21 (d, Jꢀ=ꢀ8.5 Hz, Yield: 0.27 g (65%); m.p. 193–195°C. – IR (KBr, cm−1):
2H), 7.41 (t, Jꢀ=ꢀ6.8 Hz, 1H), 7.49 (t, Jꢀ=ꢀ6.8 Hz, 1H), 7.56 νꢀ=ꢀ3430, 3132, 1636, 1507, 1282, 1026. – 1H NMR (500 MHz,
(s, 1H), 7.63 (d, Jꢀ=ꢀ6.8 Hz, 1H), 7.80–7.83 (m, 1H), 7.82 (d, CDCl3, 25°C, TMS): δꢀ=ꢀ5.26 (s, 2H), 5.56 (s, 2H), 6.95 (t,
Jꢀ=ꢀ15.7 Hz, 1H), 8.12 (d, Jꢀ=ꢀ15.7 Hz, 1H), 12.92 (s, 1H) ppm. Jꢀ=ꢀ7.5 Hz, 1H), 7.03–7.05 (m, 4H), 7.27–7.30 (m, 2H), 7.38–7.40
– 13C NMR (125 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ53.9, 62.4, 62.6, (m, 3H), 7.50 (t, Jꢀ=ꢀ7.6 Hz, 1H), 7.55 (d, Jꢀ=ꢀ15.4 Hz, 1H), 7.63 (d,
112.8, 114.5, 118.1, 118.8, 120.2, 121.4, 122.6, 123.9, 126.2, Jꢀ=ꢀ7.8 Hz, 2H), 7.89 (d, Jꢀ=ꢀ15.4 Hz, 1H), 7.93 (s, 1H), 12.92 (s,
127.0, 129.5, 129.8, 130.3, 132.1, 136.2, 141.0, 143.9, 143.9, 157.7, 1H) ppm. – 13C NMR (125 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ54.4,
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62.2, 115.3, 117.9, 118.6, 118.7, 120.1, 122.8, 127.8, 128.1, 128.9, Jꢀ=ꢀ15.1 Hz, 1H), 7.93 (d, Jꢀ=ꢀ7.8 Hz, 1H), 12.90 (s, 1H) ppm.
129.2, 129.5, 130.5, 134.3, 136.2, 144.0, 145.1, 160.5, 163.5, – 13C NMR (125 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ52.8, 56.0, 63.0,
193.6 ppm. – Anal. for C25H21N3O3: Calcd. C 72.98, H 5.14, N 113.7, 114.2, 118.2, 118.6, 118.7, 120.0, 121.6, 123.1. 127.0, 128.1,
10.21; found C 72.69, H 5.33, N 10.50.
128.8, 129.0, 129.1, 129.5, 136.2, 145.1, 145.4, 149.7, 150.3,
163.5, 193.5 ppm. – Anal. for C26H23N3O4: Calcd. C 70.73, H
5.25, N 9.52; found C 70.56, H 5.02, N 9.36.
4.4.5 (E)-1-(2-Hydroxyphenyl)-3-(4-((1-(4-methylbenzyl)-
1H-1,2,3-triazol-4-yl)methoxy)phenyl)prop-2-en-1-
one (4e)
4.4.8 (E)-1-(2-Hydroxyphenyl)-3-(3-methoxy-4-((1-(4-
methoxybenzyl)-1H-1,2,3-triazol-4-yl)methoxy)
phenyl)prop-2-en-1-one (4h)
Yield: 0.31 g (72%); m.p. 177–179°C. – IR (KBr, cm−1):
νꢀ=ꢀ3147, 1638, 1510, 1264, 1025. – 1H NMR (500 MHz, CDCl3,
25°C, TMS): δꢀ=ꢀ2.36 (s, 3H), 5.25 (s, 2H), 5.51 (s, 2H), 6.95 (t, Yield: 0.33 g (71%); m.p. 125–127°C. – IR (KBr, cm−1):
Jꢀ=ꢀ7.5 Hz, 1H), 7.02–7.04 (m, 3H), 7.19–7.22 (m, 4H), 7.48–7.51 νꢀ=ꢀ3146, 1639, 1511, 1255, 1027. – 1H NMR (500 MHz, CDCl3,
(m, 2H), 7.53 (d, Jꢀ=ꢀ15.1 Hz, 1H), 7.62 (d, Jꢀ=ꢀ8.3 Hz, 2H), 7.90 25°C, TMS): δꢀ=ꢀ3.84 (s, 3H), 3.95 (s, 3H), 5.35 (s, 2H), 5.49
(d, Jꢀ=ꢀ15.1 Hz, 1H), 7.93 (s, 1H), 12.92 (s, 1H) ppm. – 13C NMR (s, 2H), 6.92 (d, Jꢀ=ꢀ7.7 Hz, 2H), 6.98 (t, Jꢀ=ꢀ7.6 Hz, 1H), 7.06
(125 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ21.1, 54.2, 62.1, 115.3, 118.7, (d, Jꢀ=ꢀ8.5 Hz, 1H), 7.15 (d, Jꢀ=ꢀ8.5 Hz, 1H), 7.19 (s, 1H), 7.26
120.8, 121.5, 122.8, 127.0, 127.9, 128.2, 129.5, 129.8, 130.5, (d, Jꢀ=ꢀ7.7 Hz, 2H), 7.51–7.54 (m, 2H), 7.56 (d, Jꢀ=ꢀ15.3 Hz, 1H),
131.2, 136.1, 138.9, 144.0, 145.1, 160.5, 163.5, 193.6 ppm. – 7.59 (s, 1H), 7.89 (d, Jꢀ=ꢀ15.3 Hz, 1H) 7.96 (d, Jꢀ=ꢀ7.6 Hz, 1H),
Anal. for C26H23N3O3: Calcd. C 73.39, H 5.45, N 9.88; found C 12.93 (s, 1H) ppm. – 13C NMR (125 MHz, CDCl3, 25°C, TMS):
73.19, H 5.67, N 9.60.
δꢀ=ꢀ53.8, 55.3, 62.9, 63.1, 110.9, 113.7, 114.5, 118.1, 118.6, 118.7,
120.0, 121.6, 122.8, 123.1, 127.0, 128.3, 129.7, 132.1, 136.2, 143.7,
149.6, 150.2, 160.0, 163.5, 193.5 ppm. – Anal. for C27H25N3O5:
Calcd. C 68.78, H 5.34, N 8.91; found C 68.99, H 5.18, N 9.11.
4.4.6 (E)-3-(4-((1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)
methoxy)phenyl)-1-(2-hydroxyphenyl)prop-2-en-
1-one (4f)
4.4.9 (E)-3-(4-((1-(2-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)
methoxy)-3-methoxyphenyl)-1-(2-hydroxyphenyl)
prop-2-en-1-one (4j)
Yield: 0.33 g (74%); m.p. 162–164°C. – IR (KBr, cm−1):
1
νꢀ=ꢀ3215, 1644, 1509, 1471, 1364, 1195, 1043, 844, 762. – H
NMR (500 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ4.93 (s, 2H), 5.23
(s, 2H), 6.65 (t, Jꢀ=ꢀ7.6 Hz, 1H), 6.73–6.75 (m, 4H), 6.93 (d, Yield: 0.29 g (61%); m.p. 170–172°C. – IR (KBr, cm−1):
1
Jꢀ=ꢀ8.3 Hz, 2H), 7.07 (d, Jꢀ=ꢀ8.3 Hz, 2H), 7.20 (t, Jꢀ=ꢀ8.2 Hz, νꢀ=ꢀ3158, 1636, 1517, 1256, 1026, 756. – H NMR (500 MHz,
1H), 7.25 (d, Jꢀ=ꢀ15.7 Hz, 1H), 7.33 (d, Jꢀ=ꢀ8.6 Hz, 2H), 7.59 (d, CDCl3, 25°C, TMS): δꢀ=ꢀ3.94 (s, 3H), 5.36 (s, 2H), 5.68 (s,
13
Jꢀ=ꢀ15.7 Hz, 1H), 7.62 (s, 1H), 12.62 (s, 1H) ppm. – C NMR 2H), 6.96 (t, Jꢀ=ꢀ7.6 Hz, 1H), 7.04 (d, Jꢀ=ꢀ8.2 Hz, 1H), 7.14 (d,
(125 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ53.6, 62.1, 115.1, 115.3, Jꢀ=ꢀ8.2 Hz, 1H), 7.16 (s, 1H), 7.21 (d, Jꢀ=ꢀ7.6 Hz, 1H), 7.25–7.27
118.0, 118.6, 118.8, 120.1, 122.7, 128.0, 129.40, 129.44, 129.5, (m, 2H), 7.33 (t, Jꢀ=ꢀ7.5 Hz, 1H), 7.44 (d, Jꢀ=ꢀ7.6 Hz, 1H), 7.49–
130.5, 132.8, 136.2, 144.2, 145.0, 160.5, 163.5, 193.6 ppm. 7.51 (m, 2H), 7.53 (d, Jꢀ=ꢀ15.3 Hz, 1H), 7.87 (d, Jꢀ=ꢀ15.3 Hz,
13
– Anal. for C25H20ClN3O3: Calcd. C 67.34, H 4.52, N 9.42; 1H), 7.93 (d, Jꢀ=ꢀ7.6 Hz, 1H), 12.90 (s, 1H) ppm. – C NMR
found C 67.15, H 4.79, N 9.27.
(125 MHz, CDCl3, 25°C, TMS): δꢀ=ꢀ51.6, 56.1, 63.1, 111.0, 113.9,
118.2, 118.6, 118.8, 120.1, 123.1, 123.4, 127.6, 128.4, 129.5,
130.0, 130.4, 130.5, 132.2, 133.6, 136.2, 143.9, 145.4, 149.7,
150.3, 163.5, 193.5 ppm. – Anal. for C26H22ClN3O4: Calcd. C
65.62, H 4.66, N 8.83; found C 65.80, H 4.39, N 8.60.
4.4.7 (E)-3-(4-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)-
3-methoxyphenyl)-1-(2-hydroxyphenyl)prop-2-en-
1-one (4g)
Yield: 0.28 g (63%); m.p. 149–151°C. – IR (KBr, cm−1): 4.4.10 (E)-3-(4-((1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl)
νꢀ=ꢀ3134, 1639, 1508, 1259, 1027. – 1H NMR (500 MHz, CDCl3,
25°C, TMS): δꢀ=ꢀ3.92 (s, 3H), 5.34 (s, 2H), 5.53 (s, 2H), 6.95
(t, Jꢀ=ꢀ7.8 Hz, 1H), 7.03 (d, Jꢀ=ꢀ8.3 Hz, 1H), 7.12 (d, Jꢀ=ꢀ8.3 Hz,
methoxy)-3-methoxyphenyl)-1-(2-hydroxyphenyl)
prop-2-en-1-one (4k)
1H), 7.16 (s, 1H), 7.25–7.28 (m, 3H), 7.37–7.39 (m, 2H), 7.50– Yield: 0.32 g (67%); m.p. 196–198°C. – IR (KBr, cm−1):
1
7.52 (m, 2H), 7.53 (d, Jꢀ=ꢀ15.1 Hz, 1H), 7.59 (s, 1H), 7.86 (d, νꢀ=ꢀ3147, 1637, 1513, 1264, 1025, 758. – H NMR (500 MHz,
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82ꢀ ꢀA. Asadipour et al.: Synthesis and biological evaluation of chalcone-triazole hybrid derivatives
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CDCl3, 25°C, TMS): δꢀ=ꢀ3.93 (s, 3H), 5.34 (s, 2H), 5.51 (s, 2H),
6.96(t, Jꢀ=ꢀ7.8Hz, 1H), 7.03(d, Jꢀ=ꢀ8.1Hz, 1H), 7.12(d, Jꢀ=ꢀ8.1Hz,
1H), 7.17 (s, 1H), 7.21 (d, Jꢀ=ꢀ8.0 Hz, 2H), 7.26–7.27 (m, 1H),
7.35 (d, Jꢀ=ꢀ8.0 Hz, 2H), 7.49–7.51 (m, 1H), 7.52 (d, Jꢀ=ꢀ15.5 Hz,
1H), 7.59 (s, 1H), 7.87 (d, Jꢀ=ꢀ15.5 Hz, 1H), 7.93 (d, Jꢀ=ꢀ7.8 Hz,
13
1H), 12.89 (s, 1H) ppm. – C NMR (125 MHz, CDCl3, 25°C,
TMS): δꢀ=ꢀ53.6, 56.0, 63.2, 113.8, 114.2, 118.1, 118.3, 118.8,
120.1, 121.6, 122.9, 123.1, 127.0, 128.4, 129.5, 132.8, 135.0,
136.2, 144.2, 145.4, 149.7, 150.2, 163.2, 193.5 ppm. – Anal. for
C26H22ClN3O4: Calcd. C 65.62, H 4.66, N 8.83; found C 65.40,
H 4.39, N 9.05.
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(2-hydroxyphenyl)prop-2-en-1-one (4l)
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Yield: 0.37 g (73%); m.p. 180–182°C. – IR (KBr, cm−1):
νꢀ=ꢀ3234, 3103, 1688, 1641, 1510, 1259. – 1H NMR (500 MHz,
CDCl3, 25°C, TMS): δꢀ=ꢀ3.93 (s, 3H), 5.34 (s, 2H), 5.48 (s, 2H),
6.95 (t, Jꢀ=ꢀ7.4 Hz, 1H), 7.02 (d, Jꢀ=ꢀ8.2 Hz, 1H), 7.05 (s, 1H),
7.11 (d, Jꢀ=ꢀ8.2 Hz, 1H), 7.17 (s, 1H), 7.25 (d, Jꢀ=ꢀ7.2 Hz, 1H), 7.37
(s, 1H), 7.44 (d, Jꢀ=ꢀ8.3 Hz, 1H), 7.48–7.54 (m, 2H), 7.53 (d,
Jꢀ=ꢀ15.3 Hz, 1H), 7.86 (d, Jꢀ=ꢀ15.4 Hz, 1H), 7.92 (d, Jꢀ=ꢀ7.4 Hz,
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13
1H), 12.89 (s, 1H) ppm. – C NMR (125 MHz, CDCl3, 25°C,
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TMS): δꢀ=ꢀ52.9, 56.0, 62.9, 111.0, 113.7, 118.6, 118.7, 120.0,
121.6, 123.0, 123.1, 127.2, 128.4, 129.5, 129.9, 131.1, 132.3, 133.3,
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– Anal. for C26H21Cl2N3O4: Calcd. C 61.19, H 4.15, N 8.23;
found C 61.34, H 3.98, N 8.48.
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5 Supplementary information
The 1H and 13C NMR spectra of the synthesized compounds
4a–4l are given as Supplementary Information available
online (https://doi.org/10.1515/znb-2017-0115).
Acknowledgments: This study was funded and supported
by Tehran University of Medical Sciences (TUMS); Grant
no. 96-02-33-35087; and Iran National Science Foundation
(INSF).
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ꢂ83
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Supplemental Material: The online version of this article offers
supplementary material (https://doi.org/10.1515/znb-2017-0115).
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