Design, Synthesis, Antimicrobial, and Antioxidant Activity of Dimers of Chromene Containing 1,2,3-Triazole Derivatives Bearing an Alkyl Spacer

Article abstract of DOI:10.1134/S1070363219100190

A new series of chromene based 1,2,3-triazole derivatives has been synthesized by incorporating biologically active heterocyclic rings containing chromene and triazole moieties in one molecular structure. All newly synthesized compounds are characterized

Full text of DOI:10.1134/S1070363219100190

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 10, pp. 2108–2114. © Pleiades Publishing, Ltd., 2019.
Design, Synthesis, Antimicrobial, and Antioxidant Activity
of Dimers of Chromene Containing 1,2,3-Triazole Derivatives
Bearing an Alkyl Spacer1
I. Vania and K. R. S. Prasadb*
a Department of Chemistry, GDC, Kukatpally, India
b Department of Chemistry, K.L.E.F. Vaddeswaram, India
*e-mail: vaniinavolu@gmail.com
Received April 20, 2019; revised September 27, 2019; accepted October 3, 2019
Abstract—A new series of chromene based 1,2,3-triazole derivatives has been synthesized by incorporating bio-
logically active heterocyclic rings containing chromene and triazole moieties in one molecular structure.All newly
1
synthesized compounds are characterized by H and 13C NMR, mass, and IR spectra. The title compounds are
tested for their activity against different bacterial and fungal strains, and antioxidant activity. Several compounds
are determined to be potent antimicrobial and antioxidant agents.
Keywords: chromene, 1,2,3-triazole, click chemistry, alkyl spacer, antimicrobial, antioxidant
DOI: 10.1134/S1070363219100190
INTRODUCTION
dihaloalkanes 1 with sodium azide giving diazidoalkanes
2 according to the literature procedure [9]. Propargylation
of compound 3 followed by cyclization of thus formed
intermediates 4a–4d gave the corresponding cyclized
derivatives 5a–5d [10]. Propargylation of the latter com-
pounds led to the corresponding derivatives 6a–6d that
were introduced in the copper-catalyzed Huisgen [3+2]
cycloaddition reaction with diazidoalkanes 2 giving the
target chromene based 1,2,3-triazole derivatives 7a–7l.
Chromenes (benzopyran) are important medicinal
pharmacophores that make a significant structural com-
ponent of a big number of natural compounds [1–4].
Synthetic chromene derivatives demonstrate antitumor,
antivascular [5], antioxidant, antimicrobial [6, 7], anti-
fungal, and many other types of activities. Lipophilic
nature of benzopyran derivatives supports their crossing
the cell membranes [8].
The products 7a–7l were characterized by 1H and13C
NMR, IR, and mass spectra.
Many 1,2,3-triazole derivatives are well known as
compounds of high biological activity.
Antibacterial activity. All the newly synthesized com-
pounds were screened in vitro for antibacterial activity
against Gram positive Bacillus subtilis (ATCC 6633) and
Staphylococcus aureus (ATCC 6538) bacteria, and Gram
negative Escherichia coli (ATCC 11229) and Proteus
vulgaris (ATCC 29213) bacteria. Agar well-diffusion
method was used to assay the antibacterial activity against
test strains on Mueller-Henton agar plates. Gentamicin
was used as a standard antibacterial drug (Table 1). The
accumulated antibacterial activity data revealed that
compounds 7a, 7d, 7e were of the highest antibacterial
activity. The other synthesized compounds exhibited
moderate zones of inhibition of bacterial cultures.
Based on the biological significance of chromene
and triazole derivatives and our ongoing efforts in
developing newer antimicrobial agents, in the present
study we present design and synthesis of a series of
novel chromene based 1,2,3-triazole derivatives 7a–7l via
copper-catalyzed Huisgen [3+2] cycloaddition reaction.
All the synthesized compounds have been tested for their
antimicrobial activity.
RESULTS AND DISCUSSION
Synthesis of a series of chromene based 1,2,3-triazole
derivatives 7a–7l (Scheme 1) started with the reaction of
Antifungal activity. The same compounds were evalu-
ated for their in vitro antifungal activity against Asper-
gillus niger (ATCC 9029) and Candida albicans (ATCC
1
Supplementary materials are available for this article at https://
doi.org/10.1134/S1070363219100190 and are accessible for
authorized users.
2108

DESIGN, SYNTHESIS, ANTIMICROBIAL AND ANTIOXIDANT ACTIVITY
2109
Scheme 1. Synthetic route to novel chromene based 1,2,3-triazole derivatives 7a–7l.
NaN3
N3
n
N3
Br
n
Br
H2OꢀDMF, 1 : 1
1aꢀ1c
2aꢀ2c
n = 3ꢀ5
Br
R
R
O
X
5 h
R
R
dryacetone,
K2CO3
N,N-dimethyl aniline
HO
X
OH
O
O
X
OH
O
OH
Cl
reflux,3 h
O
3a, 3b
15 h
5aꢀ5d
4aꢀ4d
X = H, Cl
R = H, CH3
R
O
X
R
propargyl bromide,
dry acetone, K2CO3
O
N3
N3
+
n
reflux, 5 h
O
6aꢀ6d
2aꢀ2c
R
R
R
N
N
R
N
N
N
O
O
CuSO4·5H2O
sodium ascorbate
N
O
O
O
X
n
DMFꢀH2O
room temperature
X
O
7aꢀ7l
10231) fungal strains. Agar well-diffusion method was
used to evaluate the antifungal activity. Fluconazole was
used as a standard antifungal drug (Table 1). The com-
pound 7d demonstrated the highest antifungal activity.
Compounds 7a, 7c, 7e exhibited the promising growth
inhibitory activity. The rest of the synthesized compounds
demonstrated moderate to poor zone of inhibition against
fungal strains.
The compounds 7e, 7f, 7o exhibited strong scavenging
effects on the DPPH stable radical and the highest H2O2
radical scavenging activity (Table 2).
EXPERIMENTAL
All melting points were determined on a Stuart SMP3
melting-point apparatus and are uncorrected. IR (KBr)
spectra were recorded on a Shimadzu FTIR 8400 S spec-
trophotometer. 1H and 13C NMR spectra were measured
on a Bruker Avance-400 spectrometer using TMS as an
internal reference and CDCl3 as a solvent. Mass spectra
(EI) were measured on a Finnigan MAT 1020 mass
spectrometer. Elemental analyses were carried out on a
Karlo Erba 1106 elemental analyzer. All reactions were
Antioxidant activity. Antioxidant activity of the syn-
thesized compounds was evaluated in vitro by the 2,2-
diphenyl-1-picrylhydrazyl (DPPH) radical scavenging
assay and hydrogen peroxide. The results were compared
with the standard ascorbic acid. Most of compounds
demonstrated significant inhibitory activity (Table 2).
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VANI, PRASAD
Table 1. Antimicrobial activity of the synthesized compounds
Gram positive bacteria
Compound
Gram negative bacteria
Fungal strains
A. niger C. albicans
B. subtilis
S. aureus
E. coli
32
19
22
28
23
24
20
24
19
17
17
16
35
–
P. vulgaris
7a
29
21
18
27
23
22
16
19
16
22
13
11
33
–
26
27
22
23
27
28
18
17
24
21
16
19
16
31
–
23
17
22
26
18
14
16
17
19
13
09
11
–
19
16
18
27
22
18
16
12
14
16
12
16
–
7b
17
7c
18
7d
26
7e
23
7f
23
7g
15
7h
22
7i
19
7j
16
7k
15
7l
17
Gentamicin
Fluconazole
28
–
35
33
Synthesis of compounds 6. To the stirred mixture
of a compound 5a–5d (1 mmol) with K2CO3 (0.72 g,
2 mmol) in dry acetone (5 mL), was added propargyl bro-
mide (80% in toluene) (0.36 mL, 1.2 mmol). The reaction
mixture was refluxed for ca 5 h. After completion of the
reaction, acetone was distilled off, and the residue was
treated with 25 mL of ice cold water. The precipitate was
filtered off and washed with an excess of water to obtain
the corresponding pure compound 6a–6d.
monitored on silica gel percolated TLC plates (Merck 60
F254) and spots were visualized under UV light.
Table 2. Antioxidant activity of the synthesized compounds
Scavenging activity IC50, μM
Compound
DPPH
H2O2
7a
21.75± 1.76
23.89±0.68
28.71±0.86
35.91±0.56
16.71±1.72
16.46±0.79
29.75±1.29
43.43±1.03
31.12±0.47
32.66±0.59
21.73±1.73
21.84±1.16
78.25±3.92
27.88±1.51
28.09±0.96
26.50±0.40
33.85±0.71
16.84±0.73
19.36±1.97
28.59±0.75
36.75±0.39
38.54±0.72
29.90±0.83
23.96±1.45
21.91±1.00
92.48±2.73
7b
Synthesis of compounds 7a–7l. To the well stirred
mixture of a compound 6a–6d (1 mmol) and one of
1,3-diazidoalkanes 2a–2c (0.5 mmol) in DMF–H2O
(1 : 1 v/v) (10 mL), were added copper(II)sulphate pen-
tahydrate (0.2 mmol) and sodium ascorbate (0.5 mmol).
The mixture was stirred for 18 h at room temperature.
Upon completion of the process (as indicated by TLC),
the reaction mixture was added to 90 mLof ice cold water.
The precipitate was separated, washed twice with brine
and purified by silica gel column chromatography to af-
ford the corresponding compound 7a–7l as white solid.
7c
7d
7e
7f
7g
7h
7i
7j
1-[5-(Prop-2-yn-1-yloxy)-2H-chromen-6-yl]-
ethanone (6a). White solid, yield 95%, mp 86–88°C.
7k
7l
1
IR spectrum, ν, cm–1: 2189 (C≡C), 1637 (C=O). H
Ascorbic acid
NMR spectrum, δ, ppm: 7.63 d (1H, J = 8.36 Hz, Ar-H),
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DESIGN, SYNTHESIS, ANTIMICROBIAL AND ANTIOXIDANT ACTIVITY
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6.80–6.85 m (1H, OCH2CH=CH), 6.50 d (1H, J =
8.36 Hz, Ar-H), 5.81–5.85 m (1H, OCH2=CH), 4.90 s
(2H, OCH2), 4.71–4.74 d (2H, OCH2), 2.93 t (1H, OC–H),
2.56 s (3H, COCH3). 13C NMR spectrum, δC, ppm: 203.3
(C=O), 160.3, 159.1, 129.5, 124.1, 123.7, 115.1, 110.5,
104.3, 76.7 (C≡C–H), 74.7 (≡C–H), 62.3 (OCH2), 59.3
(OCH2), 26.7 (COCH3). MS: m/z : 229 [M + H]+. Found,
%: C 73.63; H 5.32. C14H12O3. Calculated, %: C 73.67;
H 5.30.
chromene-6,5-diyl)]diethanone (7a). Yield 92%, mp
107–109°C. IR spectrum, ν, cm–1: 1626 (C=O). 1H NMR
spectrum, δ, ppm: 8.19 s (2H, triazole-H), 7.63 d (2H,
J = 8.49 Hz, Ar-H), 6.81–6.85 m (4H, Ar-H), 5.84–5.90
m (2H, OCH2 =CH), 5.22 s (4H, OCH2), 4.94 s (4H,
OCH2), 4.44 s (4H, NCH2), 2.58 s (6H, COCH3), 2.26 t
(2H, aliphatic-CH2). 13C NMR spectrum, δC, ppm: 201.3
(C=O), 164.8, 163.7, 141.8, 128.0, 124.8, 123.9, 119.0,
114.7, 109.3, 106.9, 69.2 (OCH2), 61.4 (OCH2), 46.5
(NCH2), 30.2 (CH2), 26.8 (COCH3). MS: m/z: 582 [M +
H]+. Found, %: C 63.95; H 5.21; N 14.44. C31H30N6O6.
Calculated, %: C 63.91; H 5.19; N 14.42.
1-[2,2-Dimethyl-5-(prop-2-yn-1-yloxy)-2H-chro-
men-6-yl]ethanone (6b). Light yellow solid, yield 96%,
mp 98–99°C. IR spectrum, ν, cm–1: 2195 (C≡C), 1634
(C=O). 1H NMR spectrum, δ, ppm: 7.55 d (1H, J= 8.14 Hz,
Ar-H), 6.83–6.88 m (1H, OCH2CH=CH), 6.56 d (1H,
J = 8.14 Hz, Ar-H), 5.73–5.78 m (1H, OCH2=CH), 4.74
d (2H, OCH2), 2.90 t (1H, ≡C–H), 2.58 s (3H, COCH3),
1.56 s (6H, C(CH3)2). 13C NMR spectrum, δC, ppm: 203.1
(C=O), 160.1, 159.3, 129.2, 124.8, 123.4, 114.9, 110.6,
104.2, 76.7 (C≡C–H), 74.8 (≡C–H), 72.1 (OCH2), 59.2
(OCH2), 26.7 (COCH3), 30.1 [(CH3)2]. MS: m/z : 257
[M + H]+. Found, %: C 74.95; H 5.16.25; N 18.77.
C16H16O3. Calculated, %: C 74.98; H 5.16.29; N 18.73.
1,1'-{5,5'-[{1,1'-(Propane-1,3-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)}bis(oxy)]bis(2,2-
dimethyl-2H-chromene-6,5-diyl)}diethanone (7b).
Yield 94%, mp 122–124°C. IR spectrum, ν, cm–1: 1625
(C=O). 1H NMR spectrum, δ, ppm: 8.21 s (2H, triazole-
H), 7.65 d (2H, J = 8.49 Hz, Ar-H), 6.79–6.83 m (4H,
Ar-H), 5.82–5.88 m (2H, OCH2 =CH), 5.21 s (4H, OCH2),
4.40 s (4H, NCH2), 2.56 s (6H, COCH3), 2.22 t (2H,
aliphatic-CH2), 1.46 s (12H, CH3). 13C NMR spectrum,
δC, ppm: 201.1 (C=O), 164.2, 163.8, 141.9, 127.9, 124.8,
123.6, 117.9, 114.0, 109.5, 107.1, 69.9 [C(CH3)2], 61.4
(OCH2), 46.6 (NCH2), 30.2 (CH2), 29.0 [(CH3)2], 26.8
(COCH3). MS: m/z: 639 [M + H]+. Found, %: C 65.85;
H 6.03; N 13.13. C31H30N6O6. Calculated, %: C 65.82;
H 6.00; N 13.16.
1-[8-Chloro-5-(prop-2-yn-1-yloxy)-2H-chromen-6-
yl]ethanone (6c). White solid, yield 92%, mp 75–77°C.
IR spectrum, ν, cm–1: 2197 (C≡C), 1639 (C=O). 1H NMR
spectrum, δ, ppm: 7.65 s (1H, Ar-H), 6.71–6.76 m (1H,
OCH+CH=CH), 5.80–5.84 m (1H, OCH2=CH), 4.92 s
(2H, OCH2), 4.79–4.81 d (2H, OCH2), 2.92 t (1H, ≡C–H),
2.58 s (3H, COCH3).13C NMR spectrum, δC, ppm: 203.2
(C=O), 159.6, 159.4, 129.3, 124.3, 123.9, 118.8, 115.3,
110.4, 76.6 (C≡C–H), 74.8 (≡C–H), 61.9 (OCH2), 59.2
(OCH2), 26.8 (COCH3). MS: m/z: 263 [M + H]+. Found,
%: C 64.05; H 4.19. C14H11ClO3. Calculated, %: C 64.01;
H 4.22.
1,1'-[5,5'-{[1,1'-(Propane-1,3-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)}bis(oxy)bis(8-chlo-
ro-2H-chromene-6,5-diyl)]diethanone (7c). Yield 96%,
1
mp 118–120°C. IR spectrum, ν, cm–1: 1628 (C=O). H
NMR spectrum, δ, ppm: 8.31 s (2H, triazole-H), 7.53 s
(2H, Ar-H), 6.73 d (2H, J = 10.19 Hz, OCH2CH=CH),
5.81–5.87 m (2H, OCH2 =CH), 5.21 s (4H, OCH2), 4.93
s (4H, OCH2), 4.42 s (4H, NCH2), 2.64 s (6H, COCH3),
2.23 t (2H, aliphatic-CH2). 13C NMR spectrum, δC,
ppm: 201.1 (C=O), 164.1, 163.2, 141.8, 127.5, 124.6,
123.3, 119.1, 115.3, 114.9, 106.0, 69.5 [C(CH3)2], 61.3
(OCH2), 46.4 (NCH2), 30.1 (CH2), 26.8 (COCH3). MS:
m/z: 652 [M + H]+. Found, %: C 57.13; H 4.36; N 10.86.
C31H28Cl2N6O6. Calculated, %: C 57.15; H 4.33; N 10.88.
1-[8-Chloro-2,2-dimethyl-5-(prop-2-yn-1-yloxy)-
2H-chromen-6-yl]ethanone (6d). White solid, yield
90%, mp 94–96°C. IR spectrum, ν, cm–1: 2195 (C≡C),
1636 (C=O). 1H NMR spectrum, δ, ppm: 7.72 s (1H, Ar-
H), 6.68–6.73 m (1H, OCH2CH=CH), 5.74–5.79 m (1H,
OCH2=CH), 4.74–4.78 d (2H, OCH2), 2.91 t (1H, OC–H),
2.59 s (3H, COCH3), 1.55 s [6H, C(CH3)2]. 13C NMR
spectrum, δC, ppm: 203.2 (C=O), 159.3, 129.1, 124.9,
123.1, 119.0, 114.9, 110.5, 76.7 (C≡C–H), 74.7 (≡C–H),
72.2 (OCH2), 59.2 (OCH2), 26.7 (COCH3), 30.2 [(CH3)2].
Mass spectrum, m/z : 263 ([M + H]+. Found, %: C 66.07;
H 5.24. C16H15ClO3. Calculated, %: C 66.10; H 5.20.
1,1'-[5,5'-({[1,1'-(Propane-1,3-diyl)bis(1H-1,2,3-
triazole-4,1-diyl))bis(methylene)]bis(oxy)}bis(8-chlo-
ro-2,2-dimethyl-2H-chromene-6,5-diyl)]diethanone
(7d). Yield 95%, mp 140–142°C. IR spectrum, ν, cm–1:
1631 (C=O).
1H NMR spectrum, δ, ppm: 8.34 s (2H,
1,1'-[5,5'-({[1,1'-(Propane-1,3-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)]bis(oxy)}bis(2H-
triazole-H), 7.52 s (2H, Ar-H), 6.75 d (2H, J = 10.79 Hz,
OCH2CH =CH), 5.81–5.87 m (2H, OCH2 =CH), 5.22 s
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VANI, PRASAD
(4H, OCH2), 4.47 s (4H, NCH2), 2.61 s (6H, COCH3),
2.23 t (2H, aliphatic-CH2), 1.49 s (12H, CH3). 13C NMR
spectrum, δC, ppm: 201.1 (C=O), 164.9, 163.0, 141.7,
127.7, 124.7, 123.0, 117.9, 115.4, 114.2, 106.3, 70.1
(C–CH3)2), 61.6 (OCH2), 46.1 (NCH2), 30.1 (CH2),
29.4 (C–CH3)2), 26.7 (COCH3). MS: m/z: 708 [M + H]+.
Found, %: C 59.38; H 5.15; N 10.25. C35H36Cl2N6O6.
Calculated, %: C 59.41; H 5.13; N 10.02.
123.5, 119.1, 115.3, 114.8, 106.3, 69.7 (OCH2), 61.4
(OCH2), 48.5 (NCH2), 26.8 (COCH3), 24.6 (CH2). MS:
m/z: 597 [M + H]+. Found, %: C 57.72; H 4.58; N 12.66.
C32H30ClN6O6. Calculated, %: C 57.75; H 4.54; N 12.63.
1,1'-[5,5'-{[1,1'-(Butane-1,4-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)}bis(oxy)bis(2,2-di-
methyl-2H-chromene-6,5-diyl)]diethanone (7h). Yield
92%, mp 131–133°C. IR spectrum, ν, cm–1: 1630 (C=O).
1H NMR spectrum, δ, ppm: 8.21 s (2H, triazole-H), 7.64
s (2H, Ar-H), 6.79 d (2H, J = 10.79 Hz, OCH2CH=CH),
5.90–5.96 m (2H, OCH2CH), 5.21 s (4H, OCH2), 4.38
t (4H, NCH2), 2.57 s (6H, COCH3), 1.74–1.77 m (4H,
aliphatic-CH2), 1.49 s (12H, CH3). 13C NMR spectrum,
δC, ppm: 201.4 (C=O), 164.1, 163.2, 141.5, 127.3, 124.4,
123.6, 117.7, 115.4, 114.4, 106.5, 71.6 (OCH2), 61.4
(OCH2), 48.6 (NCH2), 29.4 (CH3), 26.7 (COCH3), 24.6
(CH2). MS: m/z: 722 [M + H]+. Found, %: C 59.95; H
5.33; N 11.61. C36H38Cl2N6O6. Calculated, %: C 59.92;
H 5.31; N 11.65.
1,1'-(5,5'-{[(1,1'-(Butane-1,4-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)]bis(oxy)}bis(2H-
chromene-6,5-diyl)]diethanone (7e). Yield 95%, mp
114–116°C. IR spectrum, ν, cm–1: 1625 (C=O). 1H NMR
spectrum, δ, ppm: 8.24 s (2H, triazole-H), 7.68 d (2H,
J = 8.58 Hz,Ar-H), 6.81–6.87 m (4H,Ar-H), 5.90–5.96 m
(2H, OCH2 =CH), 5.19 s (4H, OCH2) 4.93 s (4H, OCH2),
4.35 s (4H, NCH2), 2.56 s (6H, COCH3), 1.81–1.84 m
(4H, aliphatic-CH2). 13C NMR spectrum, δC, ppm: 201.8
(C=O), 164.3, 163.9, 141.9, 128.8, 124.5, 123.2, 119.2,
114.5, 109.6, 107.0, 69.4 (OCH2), 61.3 (OCH2), 48.4
(NCH2), 26.8 (CH3), 24.6 (CH2). MS: m/z: 597 [M +
H]+. Found, %: C 64.38; H 14.06; N 14.14. C32H32N6O6.
Calculated, %: C 64.42; H 5.41; N 14.09.
1,1'-[5,5'-{[1,1'-(Pentane-1,5-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)}bis(oxy)bis(2H-
chromene-6,5-diyl)]diethanone (7i). Yield 95%, mp
125–127°C. IR spectrum, ν, cm–1: 1625 (C=O). 1H NMR
spectrum, δ, ppm: 7.76 d (2H, J = 8.39 Hz, Ar-H), 7.62 s
(2H, triazole-H), 6.68–6.73 m (4H, Ar-H), 5.88–5.93 m
(2H, OCH2CH), 5.20 s (4H, OCH2), 4.89–4.94 m (4H,
OCH2), 4.34–4.39 t, (4H, NCH2), 2.53 s (6H, COCH3),
1.82–2.02 m (6H, aliphatic-CH2). 13C NMR spectrum,
δC, ppm: 201.4 (C=O), 164.5, 161.3, 141.1, 128.0, 124.6,
123.3, 119.3, 114.9, 109.5, 107.5, 70.1 (OCH2), 61.4
(OCH2), 47.6 (NCH2), 29.2 (CH2), 26.7 (COCH3), 23.6
(CH2). MS: m/z: 611 [M + H]+. Found, %: C 64.91; H
5.61; N 15.72. C33H34N6O6. Calculated, %: C 64.93; H
5.60; N 15.75.
1,1'-[5,5'-({[1,1'-(Butane-1,4-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)]bis(oxy)}bis(2,2-di-
methyl-2H-chromene-6,5-diyl)]diethanone (7f). Yield
96%, mp 128–130°C. IR spectrum, ν, cm–1: 1627 (C=O).
1H NMR spectrum, δ, ppm: 8.18 s (2H, triazole-H),
7.70 d (2H, J = 8.58 Hz, Ar-H), 6.80 d (2H, J = 10.79 Hz,
OCH2CH=CH), 6.75 d (2H, J = 8.58 Hz,Ar-H), 5.89–5.95
m (2H, OCH2 =CH), 5.21 s (4H, OCH2), 4.38 t (4H,
NCH2), 2.53 s (6H, COCH3), 1.79–1.82 m (4H, aliphatic-
CH2), 1.47 s (12H, CH3). 13C NMR spectrum, δC, ppm:
201.7 (C=O), 164.45, 163.6, 141.4, 127.7, 124.6, 123.4,
118.1, 114.6, 109.7, 107.1, 71.2 (CCH3)2), 61.5 (OCH2),
48.5 (NCH2), 29.1 [(CH3)2], 26.7 (COCH3), 24.8 (CH2).
MS: m/z: 597 [M + H]+. Found, %: C 66.27; H 6.20; N
12.84. C36H40N6O6. Calculated, %: C 66.24; H 6.18; N
12.88.
1,1'-[5,5'-{[1,1'-(Pentane-1,5-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)}bis(oxy)bis(2,2-
dimethyl-2H-chromene-6,5-diyl)]diethanone (7j).
Yield 96%, mp 120–122°C. IR spectrum, ν, cm–1: 1627
1,1'-[5,5'-({[1,1'-(Butane-1,4-diyl)bis(1H-1,2,3-
triazole-4,1-diyl))bis(methylene)]bis(oxy)}bis(8-
chloro-2H-chromene-6,5-diyl)]diethanone (7g). Yield
94%, mp 138–140°C. IR spectrum, ν, cm–1: 1628 (C=O).
1H NMR spectrum, δ, ppm: 8.20 s (2H, triazole-H), 7.77
s (2H, Ar-H), 6.83 d (2H, J = 10.51, OCH2 CH=CH),
5.90–5.95 m (2H, OCH2 =CH), 5.19 s (4H, OCH2), 4.93
s (4H, OCH2), 4.40 t (4H, NCH2), 2.54 s (6H, COCH3),
1.76–1.79 m (4H, aliphatic-CH2). 13C NMR spectrum,
δC, ppm: 201.5 (C=O), 164.2, 163.3, 141.2, 127.4, 124.3,
1
(C=O). H NMR spectrum, δ, ppm: 7.75 d (2H, J =
8.39 Hz, Ar-H), 7.64 s (2H, triazole-H), 6.65–6.70 m,
(4H, Ar-H), 5.83–5.88 m (2H, OCH2CH), 5.27 s (4H,
OCH2), 4.89–4.92 m (4H, OCH2), 4.37 t (4H, NCH2),
2.53 s (6H, COCH3), 1.82–2.02 m (6H, aliphatic-CH2).
13C NMR spectrum, δC, ppm: 201.8 (C=O), 164.4,
161.2, 141.3, 127.6, 124.5, 123.5, 117.8, 114.6, 109.6,
107.7, 71.3 (CCH3)2, 61.6 (OCH2), 48.0 (NCH2), 29.1
(CH2), 28.9 [(CH3)2], 26.8 (COCH3), 23.4 (CH2). MS:
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DESIGN, SYNTHESIS, ANTIMICROBIAL AND ANTIOXIDANT ACTIVITY
2113
m/z: 611 [M + H]+. Found, %: C 64.93; H 5.62; N 15.72.
C33H34N6O6. Calculated, %: C 64.90; H 5.65; N 15.70.
tives with selected concentrations were inoculated and
incubated at 37°C for 24 h for bacteria and at 28°C for
48 h for fungi. The antimicrobial activity was evaluated
by the zone of inhibition (mm) around the well.
1,1'-[5,5'-{[1,1'-(Pentane-1,5-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)}bis(oxy)bis(8-
chloro-2H-chromene-6,5-diyl)]diethanone (7k). Yield
90%, mp 148-150°C. IR spectrum, ν, cm–1: 1629 (C=O).
1H NMR spectrum, δ, ppm: 7.82 s (2H, Ar-H), 7.65 s
(2H, triazole-H), 6.59 d (2H, J = 10.51, OCH2CH=CH),
5.86–5.91 m (2H, OCH2CH), 5.21 s (4H, OCH2), 4.38
t (4H, NCH2), 2.52 s (6H, COCH3), 1.80–1.99 m (6H,
aliphatic-CH2). 13C NMR spectrum, δC, ppm: 201.9
(C=O), 164.1, 161.1, 141.2, 127.6, 124.7, 123.5, 119.7,
115.1, 114.9, 107.1, 69.9 (OCH2), 61.8 (OCH2), 48.1
(NCH2), 29.3 (CH2), 26.8 (COCH3), 24.3 (CH2). MS:
m/z: 679 [M + H]+. Found, %: C 58.36; H 4.73; N 12.35.
C33H32Cl2N6O6. Calculated, %: C 58.33; H 4.75; N 12.37.
Antioxidant activity. DPPH radical scavenging activ-
ity. Hydrogen atom or electron donating capability of the
synthesized compounds was evaluated by bleaching of
the purple methanol solution of 2,2-diphenyl-1-picrylhy-
drazyl (DPPH) [12]. To 4 mL of 0.004% (w/v) methanol
solution of DPPH, 1 mL of the test compounds (5, 10,
25, 50 and 100 μg/mL) in methanol was added. After
30 min of incubation at room temperature, the absorbance
was measured against blank at 517 nm. The percent in-
hibition of DPPH free radical formation was calculated
by the equation:
Scavenging = [(Acontrol – Asample)/Ablank]×100%.
(1)
1,1'-[5,5'-{[1,1'-(Pentane-1,5-diyl)bis(1H-1,2,3-
triazole-4,1-diyl)]bis(methylene)}bis(oxy)bis(8-chlo-
ro-2,2-dimethyl-2H-chromene-6,5-diyl)]diethanone
(7l). Yield 93%, mp 110–112°C. IR spectrum, ν, cm–1:
All tests were carried out in triplicates.
Hydrogen peroxide scavenging activity. H2O2
Scavenging ability of the compounds was determined
according to the method [13]. A solution of H2O2
(40 mM) was prepared in phosphate buffer (pH 7.4).
The test compounds at 5, 10, 25, 50, and 100 μg/mL in
3.4 mL of phosphate buffer were added to H2O2 solu-
tion (0.6 mL, 40 mM). Absorbance value of the reaction
mixture was recorded at 230 nm. Percent of scavenging
of H2O2 was calculated using Eq. (1).
1
1627 (C=O). H NMR spectrum, δ, ppm: 7.87 s (2H,
Ar-H), 7.68 s (2H, triazole-H), 6.63 d (2H, J = 10.34 Hz,
OCH2–C=CH), 5.88–5.93 m (2H, OCH2–CH), 5.23 s
(4H, OCH2), 4.45 t (4H, NCH2), 2.55 s (6H, COCH3),
1.87–2.04 m (6H, aliphatic-CH2), 1.47 s (12H, CH3).
13C NMR spectrum, δC, ppm: 201.5 (C=O), 164.1,
161.2, 141.4, 127.5, 124.7, 123.3, 117.7, 115.2, 114.5,
107.1, 71.8 (OCH2), 61.6 (OCH2), 47.7 (NCH2), 29.3
[(CH3)2], 29.1 (CH2), 26.8 (COCH3), 23.5 (CH2). MS:
m/z: 736 [M + H]+. Found, %: C 60.44; H 5.45; N 11.39.
C37H40Cl2N6O6. Calculated, %: C 60.41; H 5.48; N 11.42.
CONCLUSIONS
Simple and efficient method of synthesis of novel
chromene based 1,2,3-triazole derivatives is developed.
The newly synthesized compounds are evaluated for
antimicrobial and antioxidant activity. Antimicrobial
screening of the tested compounds indicates the products
7a, 7d, 7e as the most antibacterial active and compound
7d exhibits the highest antifungal activity. Several com-
pounds were determined as potent antioxidant agents.
Thus, the synthesized compounds can be considered as
lead compounds for further development of more potent
antimicrobial and antioxidant drug agents.
Antimicrobial assay. All the new compounds were
evaluated for antimicrobial activity against four bacterial
and two fungal cultures (100 μg/mL) by the well diffu-
sion method [11]. Simultaneously, the standard antibiotic,
gentamicin for antibacterial activity, fluconazole for an-
tifungal activity were tested against the pathogens. The
well diffusion method was carried out on nutrient agar
medium (0.5% Peptone, 0.5% NaCl and 0.3% Beef ex-
tract, Himedia, Mumbai), which was autoclaved at 121°C/
15 lbs, after which medium was cooled to 40°C and poured
into petri dishes (Borosil, S-Line). After solidification of
the content, petri dishes were sterilized by overnight in-
cubation. The medium was cultured with actively grown
(0.1 mL) selected bacterial culture with 108 cfu/mL by
spread plate technique. After few minutes wells were
created on cultured medium with the help of sterile well
borer (5 mm) and selected dilutions of synthesized deriva-
FUNDING
The authors are grateful to the KL University for provid-
ing laboratory facilities and IICT, Hyderabad for providing
analytical facilities.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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2114
VANI, PRASAD
https://doi.org/10.3390/ijms12052822
REFERENCES
8. Nicolaou,K.C.,Pfefferkorn,J.A.,Roecker,A.J.,Cao,G.Q.,
Barluenga, S., and Mitchell, H.J., J. Am. Chem. Soc., 2000,
vol. 122, p. 9939.
1. Pratap, R. and Ram, V.J., Chem. Rev., 2014, vol. 114,
p. 10476.
https://doi.org/10.1021/cr500075s
https://doi.org/10.1021/ja002033k
2. Ellis, G.P., and Lockhart, I.M., Chromenes, Chromanones,
and Chromones: The Chemistry of Heterocyclic
Compounds, Vol. 31, Ellis, G.P., Ed., New York: Wiley-
VCH, 2007, p. 1.
9. Wang,C.,Salmon,L.,Li,Q.,Igartua,M.E.,Moya,S.,Cigan-
da, R., Ruiz, J., andAstruc, D., Inorg. Chem., 2016, vol. 55,
p. 6776.
https://doi.org/10.1021/acs.inorgchem.6b01092
https://doi.org/10.1002/9780470187012.ch1
10. Wang, L,, Chen, G., Lu, X., Wang, S., Han, S., Li, Y., Ping, G.,
Jiang, X., Li, H., and Yang, J., Eur. J. Med. Chem., 2015,
vol. 89, p. 88.
3. Batista, J.M., Jr, Lopes, A.A., and Ambrósio, D.L.,
Biol. Pharm. Bull., 2008, vol. 31, p. 538.
https://doi.org/10.1248/bpb.31.538
https://doi.org/10.1016/j.ejmech.2014.10.036
11. Sen, A. and Batra, A., Int. J. Curr. Pharm. Res., 2012,
vol. 4, p. 67.
4. Thomas, N. and Zachariah, S.M., Asian J. Pharm. Clin.
Res., 2013, vol. 6, p. 11.
5. Henriette, G., Lorraine, L., Bettina, H., Clemence, D.,
Kelly, D., and Irenej, K., Mol. Cancer. Ther., 2004, vol. 3,
p. 1375.
12. Burits, M. and Bucar, F., Phytother. Res., 2000, vol. 14,
p. 323.
https://doi.org/10.1002/1099-1573(200008)14:5<323::
AID-PTR621>3.0.CO;2-Q
6. Chetan,B.S.,Nimesh,M.S.,Manish,P.P.,andRanjan,G.P.,
J. Serb. Chem. Soc., 2012, vol. 77, p. 1.
13. Ruch, R.J., Cheng, S.J., and Klaunig, J.E., Carcinogenesis,
1989, vol. 10, p. 1003.
7. Milan, M., Mirjana, M., Desanka, B., Sanja, M., Neda, N.,
and Vladimir, M., Int. J. Mol. Sci., 2011, vol. 12, p. 2822.
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