Synthesis, antimalarial and antioxidant activity of coumarin appended 1,4-disubstituted 1,2,3-triazoles

Article abstract of DOI:10.1007/s00706-021-02821-8

A series of coumarin appended triazole hybrids of biotic interest was synthesized through click chemistry approach from the coumarin based terminal alkynes and aromatic azides. All the synthesized triazoles were characterized by FT-IR, ¹H NMR,

Full text of DOI:10.1007/s00706-021-02821-8

Monatshefte für Chemie - Chemical Monthly (2021) 152:1001–1012
https://doi.org/10.1007/s00706-021-02821-8
ORIGINAL PAPER
Synthesis, antimalarial and antioxidant activity of coumarin appended
1,4‑disubstituted 1,2,3‑triazoles
C. P. Kaushik1 · Manisha Chahal1
Received: 3 April 2021 / Accepted: 5 July 2021 / Published online: 8 August 2021
© Springer-Verlag GmbH Austria, part of Springer Nature 2021
Abstract
A series of coumarin appended triazole hybrids of biotic interest was synthesized through click chemistry approach from the
coumarin based terminal alkynes and aromatic azides. All the synthesized triazoles were characterized by FT-IR, 1H NMR,
13C NMR, and HRMS and assessed for antimalarial activities against plasmodium falciparum strain. Results revealed that
most of the synthesized coumarin–triazole hybrid compounds possess moderate to good activity. Further, the synthesized
coumarin triazole hybrids were employed for antioxidant activities and were found to be potent antioxidant when compared
with standard drug.
Graphic abstract
Keywords Coumarin · 1,4-Disubstituted 1,2,3-triazoles · Click chemistry · Antimalarial activity · Antioxidant activity
Introduction
quinine, many compounds with a quinoline scafold have
displayed good antimalarial activity, such as chloroquine,
amodiaquine, piperaquine, and mefloquine. Despite the
progress in reduction of malaria cases, parasite resurgence
and developing resistance of plasmodium to clinically used
chemotherapeutic agent such as chloroquine, artemisinin,
and its derivatives are provocating the researchers to explore
new, efective, safe, and inexpensive antimalarial chemo-
types to curb malaria efectively.
Malaria, a devastating tropical parasitic disease, remains the
main cause of high morbidity and mortality among commu-
nicable diseases [1]. The protozoa Plasmodium falciparum
and Plasmodium vivax that are transmitted by Anopheles
mosquitoes is among the most prevalent species infect-
ing humans and result in large number of deaths annually,
especially in young children and pregnant women [2]. His-
torically, plants have proved to be an important source of
antimalarial drugs, like quinine and artemisinin. Quinine,
the most abundant Cinchona alkaloid, was the only known
antimalarial drug for a long time. Since the discovery of
Among the oxygen heterocycles, coumarins are privi-
leged structural motifs that have attracted much interest
in recent years because of their diverse pharmacological
properties.
Coumarin derivatives are versatile compounds as they
exhibit enormous biological activities such as, acetylcho-
linesterase inhibitor [3], anticancer [4–11], antimalarial [12],
antioxidant [13–15], antimicrobial [16–21], antitubercular
* C. P. Kaushik
kaushikcp@gmail.com
1
Department of Chemistry, Guru Jambheshwar University
of Science and Technology, Hisar, Haryana 125001, India
Vol.:(0123456789)
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1002
C. P. Kaushik, M. Chahal
[22, 23], LSD1 inhibitory [24], anti-infammatory [25–27],
antidiabetic [28], etc. refecting the prime reason for their
inclusion in the hybrid framework. In addition, hydroxy-
coumarins are recognized as prevailing chain-breaking anti-
oxidants which can avert free radical injury by scavenging
reactive oxygen species with application in parasitic dis-
eases. The action of reactive oxygen species (ROS) results
in alterations and function modulations of key biomolecules.
Antioxidants play a vital role in the body defense mechanism
by regulating the elimination of reactive oxygen species
(ROS) such as hydroxyl radicals, superoxide radicals, sin-
glet oxygen, and hydrogen peroxide radicals generated from
excessive oxidative stress and normal metabolic activities.
Triazoles represent a key motif in heterocyclic chemistry
and occupy a prime place in medicinal chemistry due to
their competence to exhibit a wide spectrum of biological
activities [29–73].
(3a)/7-(prop-2-yn-1-yloxy)-2H-chromen-2-one (3b)
were obtained from the propargylation of 7-hydroxy-2H-
chromen-2-one (1a)/4-hydroxy-2H-chromen-2-one (1b) in
acetone using potassium carbonate as a base (Scheme 1).
For the synthesis of 1-azido-4-benzylbenzene deriva-
tives 7a–7j, frstly, 4-aminophenol converted into 4-azi-
dophenol (5) using 6N hydrochloric acid, sodium nitrite,
and aqueous solution of sodium azide. Then, reaction of
4-azidophenol (5) was performed with benzyl bromide
derivatives 6a–6j in the presence of potassium carbonate
as base, to get substituted azides 7a–7j (Scheme 2).
Finally targeted 4-[[1-[4-(benzyloxy)phenyl]-1H-1,2,3-
triazol-4-yl]methoxy]-2H-chromen-2-one/7-[[1-[4-
(benzyloxy)phenyl]-1H-1,2,3-triazol-4-yl]methoxy]-2H-
chromen-2-one derivatives 8a–8v were synthesized by
click reaction of aromatic azides 5 and 7a–7j and 4-(prop-
2-yn-1-yloxy)-2H-chromen-2-one (3a)/7-(prop-2-yn-1-
yloxy)-2H-chromen-2-one (3b) in DMF:H2O using copper
sulphate pentahydrate and sodium ascorbate (Scheme 3).
The propargylation of the 7-hydroxy-2H-chromen-2-one
(1a)/4-hydroxy-2H-chromen-2-one (1b) was confrmed by
the presence of a signal in a range of δ = 5.12–5.26 ppm
In the context of attempting promising biological activity,
it may be an attractive strategy to combine both pharmaco-
phoric units, i.e., coumarin and 1,2,3-triazole in a single
framework to explore biological activities. Here, we syn-
thesized a series of coumarin appended 1,4-disubstituted
1,2,3-triazole hybrids and explore their antimalarial and
antioxidant activities.
1
(s, 2H, CH2) in the H NMR spectra. The formation of
ether linkage was confrmed by the presence of singlet in
a range of 5.30–5.51 ppm. The formation of 1,2,3-triazoles
was confrmed by the resonance of the triazolyl proton as
singlet in a range of 7.97–8.98 ppm for diferent deriva-
tives. The structural assignment was also supported by the
13C NMR spectral data, which showed the C-atom signals
corresponding to triazole derivatives. The fnal confrma-
tion was made by the HRMS analysis which showed the
presence of [M]+ or [M + 1]+ ion peaks.
Results and discussion
Chemistry
The synthetic strategy for the synthesis of com-
pounds 8a–8v is outlined in Scheme 1. Terminal
alkynes, 4-(prop-2-yn-1-yloxy)-2H-chromen-2-one
Scheme 1
1 3

Synthesis, antimalarial and antioxidant activity of coumarin appended 1,4‑disubstituted…
1003
Scheme 2
Compound
6a, 7a
R
Compound
6f, 7f
R
C6H5CH2
3-NO2C6H4CH2
4-NO2C6H4CH2
4-FC6H4CH2
4-ClC6H4CH2
4-BrC6H4CH2
6b, 7b
6c, 7c
2-CH3C6H4CH2
3-CH3C6H4CH2
4-CH3C6H4CH2
2-NO2C6H4CH2
6g, 7g
6h, 7h
6i, 7i
6d, 7d
6e, 7e
6j, 7j
3. In most of the cases, the nitro substituted analogues
exhibited weak antiplasmodial activities than unsubsti-
tuted benzyl ring.
In vitro antimalarial activities
Antimalarial potential of synthesized compounds was
measured and results are reported in Table 1. Among the
synthesized coumarin–triazole hybrids, compounds 8c, 8p,
8t, and 8v (IC50 value of 0.53, 0.38, 0.49 and 0.54 µg/cm3,
respectively) expressed better antimalarial potential. Of
these, 8p (having methyl group attached at para position
of benzyl ring) showed signifcant antimalarial potential
exhibiting IC50 values of 0.38 µg/cm3 against P. falcipa-
rum strains.
4. Interestingly, introduction of fluoro functionality at
para position of benzyl nucleus (8i and 8t) improved
antimalarial activity as compared to chloro and bromo
counterparts.
5. In most of the cases, the presence of benzyloxy group
showed a clear drift towards rise in antimalarial activity
compared to free hydroxyl group in synthesized tria-
zoles.
6. 7-Chromen-2-one containing ring derivatives showed
improved antimalarial activity compared to 4-chromen-
2-one containing ring derivatives.
Following structure–activity relationship has been drawn
from above data:
7. Incorporation of triazole ring improved antiplasmodial
activities compared to its alkyne counterparts.
1. Remarkably, the substitution of benzyl hydrogen with
methyl group at any position expressed better activity
compared to substitution with nitro group at any posi-
tion.
In vitro antioxidant activity
2. In case of 1,2,3-triazoles containing 7-chromen-2-one
ring, substitution with methyl group at para position in
benzyl ring provided the better antimalarial activity, as
compared to ortho/meta substituted counterparts while
triazole derivatives having 4-chromen-2-one ring con-
taining derivatives, methyl substituent at ortho position
of benzyl ring exhibited better activity than meta/para
substituent.
Free radical scavenging potential of synthesized compounds
was measured spectrophotometrically using 2,2-diphenyl-
1-picrylhydrazyl (DPPH) assay with ascorbic acid as stand-
ard by following the procedure reported by Kaushik et al.
Table 2 summarizes the radical scavenging activities
of all compounds, compared to the synthetic antioxidant
1 3

1004
C. P. Kaushik, M. Chahal
Scheme 3
Compound
R
Compound
R
H
H
8a
8b
8c
8d
8e
8f
8l
8m
8n
8o
8p
8q
8r
C6H5CH2
C6H5CH2
2-CH3C6H4CH2
3-CH3C6H4CH2
4-CH3C6H4CH2
2-NO2C6H4CH2
3-NO2C6H4CH2
4-NO2C6H4CH2
4-FC6H4CH2
2-CH3C6H4CH2
3-CH3C6H4CH2
4-CH3C6H4CH2
2-NO2C6H4CH2
3-NO2C6H4CH2
4-NO2C6H4CH2
4-FC6H4CH2
8g
8h
8i
8s
8t
4-ClC6H4CH2
4-BrC6H4CH2
4-ClC6H4CH2
4-BrC6H4CH2
8j
8u
8v
8k
1 3

Synthesis, antimalarial and antioxidant activity of coumarin appended 1,4‑disubstituted…
1005
Table 1 Antimalarial activity of coumarin appended 1,4-disubstituted
1,2,3-triazoles 8a–8v
4. In case of scafolds carrying –CH3 groups, those with
methyl substituent at meta position of benzyl ring are
more active than ortho and para congeners.
5. Triazoles with –NO2 groups at meta position of benzyl
ring were found to show diligent activity than ortho and
para congeners.
Compound
IC50/µg cm−3
Compound
IC50/µg cm−3
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
1.52
0.84
0.53
1.05
2.18
0.98
0.60
1.22
0.70
1.72
1.25
0.268
8l
2.20
0.73
0.93
0.78
0.38
1.20
1.32
1.20
0.49
0.86
0.54
0.268
8m
8n
6. The presence of fuoro group on benzyl ring imparted
better antioxidant activity than chloro and bromo coun-
terparts.
8o
8p
8q
7. Among the synthesized coumarin–triazole hybrids, com-
pounds 8d and 8m showed better antioxidant potential
in the series.
8r
8s
8t
8u
8k
Quinine
8v
Quinine
Conclusion
Table 2 In vitro antioxidant activity of coumarin appended 1,4-disub-
stituted 1,2,3-triazoles 8a–8v
In nut shell, synthesis of coumarin appended 1,4-disubsti-
tuted 1,2,3-triazole hybrids using click chemistry has been
described. All the synthesized compounds were screened for
in vitro antimalarial and antioxidant activities. Some of the
coumarin–triazole hybrids exhibited promising antimalarial
(8c, 8p, 8t, and 8v) and antioxidant (8d and 8m) activities.
The compound 8p showed encouraging antimalarial poten-
tial when compared to standard drug quinine at same dosage.
Compound
IC50/µg cm−3
Compound
IC50/µg cm−3
8a
6.68
8.75
4.63
3.33
4.42
9.74
6.27
8.65
6.25
6.39
6.41
1.23
8l
5.82
3.86
7.01
4.81
5.82
7.26
5.24
6.36
5.11
5.69
6.21
8b
8m
8n
8o
8p
8q
8r
8s
8c
8d
8e
8f
8g
Experimental
8h
8i
8t
8u
8v
All chemicals were purchased from Alfa Aesar, Hi-Media,
and Sigma–Aldrich and used without further purifcation.
Compounds and reaction progress were routinely analyzed
on the silica gel plates (SIL G/UV254, ALUGRAM) visu-
alized under UV at wavelength 254 nm. Melting points of
compounds were determined in open capillary tubes. High
resolution mass spectrometry (HRMS) was carried out on
Bruker micro TOF Q-II spectrometer. Nuclear magnetic
resonance (NMR) spectra were determined on BRUKER
AVANCE II spectrometer operating at 400 MHz (1H) and
100 MHz (13C), in DMSO-d6 and CDCl3 as solvent. Chemi-
cal shifts (δ) are given in parts per million downfeld from
8j
8k
Ascorbic acid
ascorbic acid. Several compounds showed excellent free
radical scavenging activity.
1. The presence of electron donating group on benzyl ring
of synthesized triazoles increases antioxidant potential
compared to electron withdrawing group. Remarkably,
the substitution of benzylic hydrogen with methyl group
at any position showed better activity compared to sub-
stitution with nitro group.
1
tetramethylsilane (TMS). H NMR spectra are reported
in order: multiplicity, coupling constant (J value) in hertz
(Hz), and number of protons; signals were characterized
as s (singlet), d (doublet), t (triplet), m (multiplet), and Ar
(aryl). The IR spectra were recorded using SHIMAZDU IR
AFFINITY-I FTIR spectrometer using potassium bromide
(KBr) powder and values are given in cm−1. All the synthe-
sized compounds were screened for antimalarial activity in
the Microcare Laboratory & TRC, Surat, Gujarat.
2. 7-Chromen-2-one ring containing triazoles favored anti-
oxidant activity compared to 4-chromen-2-one deriva-
tives.
3. Methyl substituted 1,2,3-triazoles have better radical
scavenging activity as compared to nitro substituted
triazoles.
1 3

1006
C. P. Kaushik, M. Chahal
4‑[[1‑(4‑Hydrox yphenyl)‑1H‑1, 2, 3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8a, C18H13N3O4) Brown
solid; yield: 79%; m.p.: 158–160 °C; FT-IR (KBr): V =3398
(O–H str.), 3182 (C–H str. triazole), 3078 (C–H str. aromatic
ring), 2928 (C–H str., aliphatic), 1719 (C=O str. lactone),
1617, 1512 (C=C str., aromatic ring), 1328 (C–N), 1132
General procedure for the synthesis of terminal
alkynes 3a, 3b
7-Hydroxy-2H-chromen-2-one (1a)/4-hydroxy-2H-
chromen-2-one (1b) (1.0 mmol) was taken in 20 cm3 acetone
in a round-bottomed fask. To this, anhydrous potassium car-
bonate (1.5 mmol) was added and the resulting suspension
was refuxed for 30 min. Propargyl bromide (1.5 mmol) was
added slowly to the reaction mixture and the reaction mix-
ture was further refuxed for 7–8 h. Progress of the reaction
was monitored by TLC. After the completion of reaction,
reaction content was poured into crushed ice, the separated
solid was fltered and recrystallized using ethyl acetate to get
the desired alkynes 3a, 3b [74].
1
(C–O) cm−1; H NMR (400 MHz, DMSO-d6): δ = 7.97
(s, 1H, C–H triazole), 7.95 (s, 1H), 7.63 (s, 1H), 7.61 (s,
1H), 7.015 (d, J = 4.0 Hz, 2H), 6.965 (d, J = 4.0 Hz, 1H),
6.945 (d, J = 4.0 Hz, 1H), 6.29 (s, 1H), 6.27 (s, 1H), 4.90
(3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ = 160.71,
155.64, 144.78, 130.06, 113.49, 113.42, 102.28, 79.46,
79.04, 56.60 ppm; HRMS: m/z calculated for C18H13N3O4
([M+H]+) 336.0906, found 336.0904.
4‑[[1‑[4‑(Benzyloxy)phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8b, C25H19 N3O4) Brown
solid; yield: 79%; m.p.: 168–170 °C; FT-IR (KBr): V =3447
(O–H str.), 3179 (C–H str. triazole), 3086 (C–H str. aro-
matic ring), 2937 (C–H str., aliphatic), 1718 (C=O str. lac-
tone), 1618, 1510 (C=C str., aromatic ring), 1335 (C–N),
General procedure for the synthesis of aromatic
azides 5, 7a–7j
To the stirred cold solution of aminophenol 4 in dichlo-
romethane, 6N hydrochloric acid (15–20 cm3) was added
followed by addition of saturated solution of sodium nitrite.
After 30 min, aqueous solution of sodium azide (3.0 mmol)
was added dropwise to the reaction mixture at 0–5 ºC and
stirred the content for 2–3 h. After completion of reaction,
as indicated by TLC, the product was extracted with dichlo-
romethane. The solvent was dried with anhydrous sodium
sulphate and evaporated under reduced pressure to get aro-
matic azide 5. Further, the synthesis of substituted aromatic
azides [75] 7a–7j was carried out by the reaction of aromatic
azide 5 with aralkyl bromides 6a–6j in dimethylformamide
in the presence of potassium carbonate as a base with contin-
uous stirring of 4–5 h. The progress of reaction was judged
by TLC. On completion of reaction, cold water was poured
into the reaction mixture when precipitates of fnal com-
pounds 7a–7j appeared, which were fltered, washed with
cold water, and dried.
1
1142 (C–O) cm−1; H NMR (400 MHz, CDCl3): δ = 8.09
(s, 1H, C–H triazole), 7.84 (d, J = 8.0 Hz, 1H), 7.68 (d,
J = 8.0 Hz, 2H), 7.59–7.54 (m, 1H), 7.47–7.36 (m, 6H),
7.26 (d, J=8.0 Hz, 1H), 7.14 (d, J=8.0 Hz, 2H), 5.93 (s,
1H), 5.44 (s, 2H), 5.16 (s, 2H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 165.00, 162.62, 159.29, 153.39, 136.20,
132.61, 130.33, 128.74, 128.30, 127.49, 123.96, 123.18,
122.40, 121.81, 116.82, 115.89, 115.69, 115.47, 91.26,
70.44, 62.66 ppm; HRMS: m/z calculated for C25H19 N3O4
([M+H]+) 426.1409, found 426.1413.
4‑[[1‑[4‑[(2‑Methylbenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8c, C26H21N3O4) Brown solid;
yield: 79%; m.p.: 212–214 °C; FT-IR (KBr): V =3412 (O–H
str.), 3167 (C–H str. triazole), 3071 (C–H str. aromatic ring),
2923 (C–H str., aliphatic), 1719 (C=O str. lactone), 1623,
1517 (C=C str., aromatic ring), 1348 (C–N), 1121 (C–O)
1
cm−1; H NMR (400 MHz, CDCl3): δ = 8.09 (s, 1H, C–H
triazole), 7.85 (d, J=8.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 2H),
7.58 (t, J=8.0 Hz, 1H), 7.435 (d, J=4.0 Hz, 1H), 7.35 (d,
J=8.0 Hz, 1H), 7.31–7.26 (m, 5H), 7.16 (d, J=8.0 Hz, 1H),
6.99 (s, 1H), 5.94 (s, 1H), 5.45 (s, 2H), 5.14 (s, 2H), 2.42 (s,
3H, –CH3) ppm; 13C NMR (100 MHz, CDCl3): δ=164.98,
162.55, 159.39, 153.42, 138.14, 133.17, 132.58, 130.27,
129.40, 129.30, 127.61, 123.93, 123.17, 122.37, 121.79,
119.99, 116.81, 116.23, 115.91, 115.49, 91.28, 70.42,
62.68, 21.20 ppm; HRMS: m/z calculated for C26H21N3O4
([M+H]+) 440.1566, found 440.1601.
General procedure for coumarin appended
1,4‑disubstituted 1,2,3‑triazoles 8a–8v
To a solution of aromatic azides 5, 7a–7j and coumarin
based alkynes 3a, 3b in N,N-dimethylformamide, catalytic
amount of copper sulphate pentahydrate (CuSO4·5H2O),
dissolved in water and sodium ascorbate were added. The
resulting mixture was stirred for 6–12 h at ambient tempera-
ture until the starting material was consumed as refected
from TLC. After the completion of reaction, reaction mix-
ture was quenched with ice-cold water and ammonia solu-
tion, when precipitates of the fnal triazole appeared. The
precipitates were fltered and recrystallized from ethyl ace-
tate to yield the pure 1,4-disubstituted 1,2,3-triazoles 8a–8v.
4‑[[1‑[4‑[(3‑Methylbenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8d, C26H21N3O4) Brown solid;
yield: 79%; m.p.: 172–174 °C; FT-IR (KBr): V =3435 (O–H
1 3

Synthesis, antimalarial and antioxidant activity of coumarin appended 1,4‑disubstituted…
1007
str.), 3151 (C–H str. triazole), 3079 (C–H str. aromatic ring),
2925 (C–H str., aliphatic), 1718 (C=O str. lactone), 1618,
1517 (C=C str., aromatic ring), 1345 (C–N), 1138 (C–O)
1518 (C=C str., aromatic ring), 1350 (C–N), 1139 (C–O)
cm−1; 1H NMR (400 MHz, CDCl3): δ=8.30 (d, J=8.0 Hz,
2H), 8.10 (s, 1H, C–H triazole), 7.85–7.83 (m, 1H), 7.715
(d, J = 12.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H), 7.60–7.56
(m, 2H), 7.37–7.34 (m, 2H), 7.16–7.13 (m, 2H), 5.93 (s,
1H), 5.45 (s, 2H), 5.27 (s, 2H) ppm; 13C NMR (100 MHz,
DMSO-d6): δ = 164.18, 161.88, 153.26, 134.59, 133.47,
129.81, 125.45, 124.91, 123.27, 122.61, 117.06, 116.35,
115.40, 92.18, 80.71, 77.68, 57.89 ppm; HRMS: m/z calcu-
lated for C25H18N4O6 ([M+H]+) 471.1226, found 471.1225.
1
cm−1; H NMR (400 MHz, CDCl3): δ = 8.09 (s, 1H, C–H
triazole), 7.85 (d, J=8.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 2H),
7.58 (t, J=8.0 Hz, 1H), 7.435 (d, J=4.0 Hz, 1H), 7.35 (d,
J = 8.0 Hz, 1H), 7.31–7.26 (m, 5H), 7.16 (d, J = 8.0 Hz,
1H), 6.99 (s, 1H), 5.94 (s, 1H), 5.45 (s, 2H), 5.14 (s, 2H),
2.42 (s, 3H, –CH3) ppm; 13C NMR (100 MHz, CDCl3):
δ=164.94, 162.13, 153.42, 138.46, 136.11, 132.57, 129.03,
128.61, 128.18, 124.55, 123.93, 123.16, 122.46, 115.96,
91.34, 70.55, 63.35, 21.39 ppm; HRMS: m/z calculated
C26H21N3O4 ([M+H]+) 440.1566, found 440.1575.
4‑[[1‑[4‑[(4‑Nitrobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8h, C25H18N4O6) Brown
solid; yield: 79%; m.p.: 174–176 °C; FT-IR (KBr): V =3422
(O–H str.), 3238 (C–H str. triazole), 3076 (C–H str. aromatic
ring), 2918 (C–H str., aliphatic), 1718 (C=O str. lactone),
1623, 1518 (C=C str., aromatic ring), 1346 (C–N), 1141
4‑[[1‑[4‑[(4‑Methylbenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8e, C26H21N3O4) Brown
solid; yield: 79%; m.p.: 188–190 °C; FT-IR (KBr): V =3396
(O–H str.), 3131 (C–H str. triazole), 3074 (C–H str. aromatic
ring), 2921 (C–H str., aliphatic), 1728 (C=O str. lactone),
1624, 1519 (C=C str., aromatic ring), 1327 (C–N), 1138
(C–O) cm−1; 1H NMR (400 MHz, CDCl3): δ=8.08 (s, 1H,
C–H triazole), 7.84 (d, J=8.0 Hz, 1H), 7.67 (d, J=8.0 Hz,
2H), 7.59–7.55 (m, 1H), 7.36 (d, J=8.0 Hz, 3H), 7.24 (d,
J=8.0 Hz, 2H), 7.13 (d, J=8.0 Hz, 2H), 6.97 (s, 1H), 5.93
(s, 1H), 5.44 (s, 2H), 5.12 (s, 2H), 2.40 (s, 3H, –CH3) ppm;
13C NMR (100 MHz, CDCl3): δ=164.98, 162.55, 159.39,
153.42, 138.14, 133.17, 132.58, 130.27, 129.40, 129.30,
127.61, 123.93, 123.17, 122.37, 121.79, 119.99, 116.81,
116.23, 115.91, 115.49, 91.28, 70.42, 62.68, 21.20 ppm;
HRMS: m/z calculated C26H21N3O4 ([M+ H]+) 440.1566,
found 440.1582.
1
(C–O) cm−1; H NMR (400 MHz, CDCl3): δ = 8.30 (d,
J=8.0 Hz, 2H), 8.10 (s, 1H, C–H triazole), 7.85–7.83 (m,
1H), 7.73–7.70 (m, 2H), 7.66 (d, J=8.0 Hz, 2H), 7.60–7.56
(m, 2H), 7.355 (d, J=12.0 Hz, 2H), 7.145 (d, J=12.0 Hz,
2H), 5.93 (s, 1H), 5.45 (s, 2H), 5.27 (s, 2H) ppm; 13C NMR
(100 MHz, CDCl3): δ = 164.95, 162.59, 158.58, 154.24,
153.39, 142.07, 132.63, 127.66, 123.97, 123.13, 122.53,
116.84, 115.85, 115.44, 91.29, 69.05, 62.61 ppm; HRMS:
m/z calculated for C25H18N4O6 ([M+H]+) 471.1226, found
471.1211.
4‑[[1‑[4‑[(4‑Fluorobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8i, C25H18FN3O4) Brown
solid; yield: 79%; m.p.: 210–212 °C; FT-IR (KBr): V =3409
(O–H str.), 3155 (C–H str. triazole), 3077 (C–H str. aromatic
ring), 2918 (C–H str., aliphatic), 1720 (C=O str. lactone),
1623, 1510 (C=C str., aromatic ring), 1330 (C–N), 1144
(C–O) cm−1; 1H NMR (400 MHz, DMSO-d6): δ=8.95 (s,
1H, C–H triazole), 7.83–7.78 (m, 3H), 7.65–7.62 (m, 1H),
7.53–7.48 (m, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.33–7.29
(m, 1H), 7.21 (t, J = 8.0 Hz, 4H), 6.17 (s, 1H), 5.47 (s,
2H), 5.15 (s, 2H) ppm; 13C NMR (100 MHz, DMSO-d6):
δ = 164.82, 162.305 (d, J = 243 Hz, 1C), 162.00, 158.84,
153.25, 142.49, 133.345 (d, J = 5 Hz, 1C), 130.555 (d,
J = 9 Hz, 1C), 124.68, 123.82, 123.50, 122.42, 116.93,
116.28, 115.785 (d, J=21 Hz, 1C), 115.68, 115.53, 91.92,
69.37, 63.33 ppm; HRMS: m/z calculated for C25H18FN3O4
([M+H]+) 444.1315, found 444.1346.
4‑[[1‑[4‑[(2‑Nitrobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8f, C25H18N4O6) Brown solid;
yield: 79%; m.p.: 176–178 °C; FT-IR (KBr): V =3427 (O–H
str.), 3239 (C–H str. triazole), 3077 (C–H str. aromatic ring),
2918 (C–H str., aliphatic), 1718 (C=O str. lactone), 1610,
1517 (C=C str., aromatic ring), 1341 (C–N), 1128 (C–O)
cm−1; 1H NMR (400 MHz, CDCl3): δ=8.30 (d, J=8.0 Hz,
2H), 8.10 (s, 1H, C–H triazole), 7.85–7.83 (m, 1H), 7.73–
7.70 (m, 2H), 7.66 (d, J=8.0 Hz, 2H), 7.60–7.56 (m, 2H),
7.37–7.34 (m, 2H), 7.16–7.13 (m, 2H), 5.93 (s, 1H), 5.45
(s, 2H), 5.27 (s, 2H) ppm; 13C NMR (100 MHz, DMSO-
d6): δ = 164.18, 161.88, 153.26, 134.59, 133.47, 129.81,
125.45, 124.91, 123.27, 122.61, 117.06, 116.35, 115.40,
92.18, 80.71, 77.68, 57.89 ppm; HRMS: m/z calculated for
C25H18N4O6 ([M+H]+) 471.1226, found 471.1243.
4‑[[1‑[4‑[(4‑Chlorobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8j, C25H18ClN3O4) Brown
solid; yield: 79%; m.p.: 188–190 °C; FT-IR (KBr): V =3380
(O–H str.), 3145 (C–H str. triazole), 3073 (C–H str. aromatic
ring), 2928 (C–H str., aliphatic), 1720 (C=O str. lactone),
1610, 1517 (C=C str., aromatic ring), 1329 (C–N), 1124
(C–O) cm−1; 1H NMR (400 MHz, DMSO-d6): δ=8.98 (s,
4‑[[1‑[4‑[(3‑Nitrobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8g, C25H18N4O6) Brown solid;
yield: 79%; m.p.: 186–188 °C; FT-IR (KBr): V =3421 (O–H
str.), 3145 (C–H str. triazole), 3088 (C–H str. aromatic ring),
2922 (C–H str., aliphatic), 1720 (C=O str. lactone), 1622,
1 3

1008
C. P. Kaushik, M. Chahal
1H, C–H triazole), 7.84 (t, J=8.0 Hz, 3H), 7.72–7.63 (m,
2H), 7.50 (dd, J=16.0, 8.0 Hz, 5H), 7.35 (t, J=8.0 Hz, 1H),
7.24 (d, J = 8.0 Hz, 1H), 6.21 (s, 1H), 5.51 (s, 2H), 5.21
(s, 2H) ppm; 13C NMR (100 MHz, DMSO-d6): δ=164.83,
161.99, 158.76, 153.25, 142.50, 136.20, 133.31, 133.02,
130.62, 130.04, 128.96, 124.68, 123.82, 123.50, 122.45,
116.91, 116.32, 115.54, 91.91, 69.25, 63.32 ppm; HRMS:
m/z calculated for C25H18ClN3O4 ([M + H]+) 460.0986,
([M+3]+) 462.0956, found ([M+H]+) 460.0982, ([M+3]+)
462.0960.
J=6.4 Hz, 2H), 7.37 (t, J=8.0 Hz, 2H), 7.315 (d, J=4.0 Hz,
1H), 7.20–7.15 (m, 3H), 7.015 (d, J=4.0 Hz, 1H), 6.275 (d,
J=4.0 Hz, 1H), 5.30 (s, 2H), 5.15 (s, 2H) ppm; 13C NMR
(100 MHz, DMSO-d6): δ=161.58, 160.83, 158.94, 155.83,
144.85, 143.42, 137.17, 130.57, 130.11, 129.03, 128.52,
128.33, 123.72, 122.42, 116.31, 113.45, 113.28, 102.11,
70.10, 62.13 ppm; HRMS: m/z calculated for C25H19 N3O4
([M+H]+) 426.1409, found 426.1443.
7‑[[1‑[4‑[(2‑Methylbenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8n, C26H21N3O4) Brown solid;
yield: 79%; m.p.: 170–172 °C; FT-IR (KBr): V =3387 (O–H
str.), 3143 (C–H str. triazole), 3073 (C–H str. aromatic
ring), 2928 (C–H str., aliphatic), 1717 (C=O str. lactone),
1619, 1518 (C=C str., aromatic ring), 1329 (C–N), 1140
(C–O) cm−1; 1H NMR (400 MHz, CDCl3): δ=8.10 (s, 1H,
C–H triazole), 7.84 (d, J=8.0 Hz, 1H), 7.69 (d, J=8.0 Hz,
2H), 7.59–7.54 (m, 1H), 7.43 (d, J=8.0 Hz, 1H), 7.34 (d,
J=8.0 Hz, 1H), 7.31–7.23 (m, 4H), 7.15 (d, J=8.0 Hz, 2H),
5.93 (s, 1H), 5.44 (s, 2H), 5.13 (s, 2H), 2.42 (s, 3H, –CH3)
ppm; 13C NMR (100 MHz, CDCl3): δ = 160.97, 159.26,
155.80, 143.21, 138.10, 133.22, 129.39, 128.96, 127.60,
116.07, 113.62, 113.14, 112.75, 102.33, 70.42, 21.18 ppm;
HRMS: m/z calculated for C26H21N3O4 ([M+H]+) 440.1532,
found 440.1595.
4‑[[1‑[4‑[(4‑Bromobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8k, C25H18BrN3O4) Brown
solid; yield: 79%; m.p.: 216–218 °C; FT-IR (KBr): V =3394
(O–H str.), 3147 (C–H str. triazole), 3071 (C–H str. aromatic
ring), 2918 (C–H str., aliphatic), 1719 (C=O str. lactone),
1621, 1517 (C=C str., aromatic ring), 1348 (C–N), 1142
(C–O) cm−1; 1H NMR (400 MHz, DMSO-d6): δ=8.95 (s,
1H, C–H triazole), 7.84–7.77 (m, 3H), 7.65–7.60 (m, 1H),
7.57 (d, J=8.0 Hz, 2H), 7.42–7.36 (m, 3H), 7.33–7.28 (m,
1H), 7.19 (d, J=8.0 Hz, 2H), 6.17 (s, 1H), 5.47 (s, 2H), 5.15
(m, 2H) ppm; 13C NMR (100 MHz, DMSO-d6): δ=164.88,
162.09, 158.77, 153.30, 142.56, 136.67, 133.39, 131.96,
130.66, 130.43, 124.76, 123.89, 123.57, 122.49, 121.63,
117.00, 116.35, 115.57, 91.98, 69.28, 63.39 ppm; HRMS:
m/z calculated for C25H18BrN3O4 ([M + H]+) 504.0481,
([M+3]+) 506.0460, found ([M+H]+) 504.0546, ([M+3]+)
506.0486.
7‑[[1‑[4‑[(3‑Methylbenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8o, C26H21N3O4) Brown
solid; yield: 79%; m.p.: 180–182 °C; FT-IR (KBr): V =3436
(O–H str.), 3145 (C–H str. triazole), 3085 (C–H str. aromatic
ring), 2914 (C–H str., aliphatic), 1727 (C=O str. lactone),
1610, 1515 (C=C str., aromatic ring), 1348 (C–N), 1128
(C–O) cm−1; 1H NMR (400 MHz, CDCl3): δ=8.02 (s, 1H,
C–H triazole), 7.67–7.644 (m, 3H), 7.42 (d, J = 8.0 Hz,
1H), 7.34–7.24 (m, 3H), 7.185 (d, J=4.0 Hz, 1H), 7.12 (d,
J=8.0 Hz, 2H), 7.02–6.96 (m, 2H), 6.29 (d, J=8.0 Hz, 1H),
5.36 (s, 2H), 5.11 (s, 2H), 2.40 (s, 3H, -CH3) ppm; 13C NMR
(100 MHz, CDCl3): δ = 161.29, 160.95, 159.29, 155.79,
143.22, 138.46, 136.17, 129.02, 128.97, 128.61, 128.20,
124.56, 122.46, 115.96, 113.61, 113.13, 112.74, 102.31,
70.54, 21.39 ppm; HRMS: m/z calculated for C26H21N3O4
([M+H]+) 440.1532, found 440.1601.
7‑[[1‑(4‑Hydrox yphenyl)‑1H‑1, 2, 3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8l, C18H13N3O4) Brown
solid; yield: 79%; m.p.: 174–176 °C; FT-IR (KBr): V =3398
(O–H str.), 3274 (C–H str. triazole), 3081 (C–H str. aromatic
ring), 2917 (C–H str., aliphatic), 1718 (C=O str. lactone),
1611, 1505 (C=C str., aromatic ring), 1343 (C–N), 1130
1
(C–O) cm−1; H NMR (400 MHz, DMSO-d6): δ = 7.97
(s, 1H, C–H triazole), 7.95 (s, 1H), 7.63 (s, 1H), 7.61 (s,
1H), 7.015 (d, J = 4.0 Hz, 2H), 6.965 (d, J = 4.0 Hz, 1H),
6.945 (d, J = 4.0 Hz, 1H), 6.29 (s, 1H), 6.27 (s, 1H), 4.90
(3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ = 160.71,
155.64, 144.78, 130.06, 113.49, 113.42, 102.28, 79.46,
79.04, 56.60 ppm; HRMS: m/z calculated for C18H13N3O4
([M+H]+) 336.0906, found 336.0901.
7‑[[1‑[4‑[(4‑Methylbenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8p, C26H21N3O4) Brown solid;
yield: 79%; m.p.: 208–210 °C; FT-IR (KBr): V = 3396
(O–H str.), 3153 (C–H str. triazole), 3082 (C–H str. aro-
matic ring), 2926 (C–H str., aliphatic), 1722 (C=O str. lac-
tone), 1618, 1510 (C=C str., aromatic ring), 1346 (C–N),
7‑[[1‑[4‑(Benzyloxy)phenyl)‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8m, C25H19 N3O4) Brown
solid; yield: 79%; m.p.: 206–208 °C; FT-IR (KBr):
V = 3392 (O–H str.), 3145 (C–H str. triazole), 3089 (C–H
str. aromatic ring), 2918 (C–H str., aliphatic), 1716 (C=O
str. lactone), 1618, 1516 (C=C str., aromatic ring), 1346
1
1124 (C–O) cm−1; H NMR (400 MHz, CDCl3): δ = 8.02
1
(C–N), 1128 (C–O) cm−1; H NMR (400 MHz, DMSO-
(s, 1H, C–H triazole), 7.68–7.63 (m, 3H), 7.44–7.41 (m,
1H), 7.35 (d, J=8.0 Hz, 2H), 7.23 (d, J=7.8 Hz, 2H), 7.11
(d, J=8.0 Hz, 2H), 7.01–6.97 (m, 2H), 6.295 (d, J=8.0 Hz,
d6): δ=8.85 (s, 1H, C–H triazole), 7.97 (d, J=8.0 Hz, 1H),
7.77 (d, J=8.0 Hz, 2H), 7.62 (d, J=8.0 Hz, 1H), 7.44 (d,
1 3

Synthesis, antimalarial and antioxidant activity of coumarin appended 1,4‑disubstituted…
1009
1H), 5.36 (s, 2H), 5.11 (s, 2H), 2.39 (s, 3H, –CH3) ppm;
13C NMR (100 MHz, CDCl3): δ=160.97, 159.26, 155.80,
143.21, 138.10, 133.22, 129.39, 128.96, 127.60, 116.07,
113.62, 113.14, 112.75, 102.33, 70.42, 21.18 ppm; HRMS:
m/z calculated for C26H21N3O4 ([M+H]+) 440.1532, found
440.1599.
m/z calculated for C25H18N4O6 ([M+H]+) 471.1226, found
471.1301.
7‑[[1‑[4‑[(4‑Fluorobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8t, C25H18FN3O4) Brown
solid; yield: 79%; m.p.: 244–246 °C; FT-IR (KBr): V =3389
(O–H str.), 3143 (C–H str. triazole), 3087 (C–H str. aromatic
ring), 2937 (C–H str., aliphatic), 1718 (C=O str. lactone),
1610, 1514 (C=C str., aromatic ring), 1344 (C–N), 1116
7‑[[1‑[4‑[(2‑Nitrobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8q, C25H18N4O6) Brown solid;
yield: 79%; m.p.: 206–208 °C; FT-IR (KBr): V =3396 (O–H
str.), 3159 (C–H str. triazole), 3095 (C–H str. aromatic ring),
2928 (C–H str., aliphatic), 1722 (C=O str. lactone), 1622,
1517 (C=C str., aromatic ring), 1352 (C–N), 1145 (C–O)
1
(C–O) cm−1; H NMR (400 MHz, DMSO-d6): δ = 8.86
(s, 1H, C–H triazole), 7.97 (d, J = 8.0 Hz, 1H), 7.78 (d,
J=8.0 Hz, 2H), 7.63 (d, J=8.0 Hz, 1H), 7.52–7.47 (m, 2H),
7.23–7.17 (m, 5H), 7.04–7.01 (m, 1H), 6.28 (d, J=8.0 Hz,
1H), 5.31 (s, 2H), 5.14 (s, 2H) ppm; 13C NMR (100 MHz,
DMSO-d6): δ=164.82, 162.305 (d, J=243 Hz, 1C), 162.00,
158.84, 153.25, 142.49, 133.345 (d, J=5 Hz, 1C), 130.555
(d, J=9 Hz, 1C), 124.68, 123.82, 123.50, 122.42, 116.93,
116.28, 115.785 (d, J=21 Hz, 1C), 115.68, 115.53, 91.92,
69.37, 63.33 ppm; HRMS: m/z calculated for C25H18FN3O4
([M+H]+) 444.1218, found 444.1350.
1
cm−1; H NMR (400 MHz, CDCl3): δ = 8.37 (s, 1H, C–H
triazole), 8.24 (d, J = 8.0 Hz, 1H), 8.04 (s, 1H), 7.81 (d,
J = 8.0 Hz, 1H), 7.72–7.64 (m, 4H), 7.43 (d, J = 8.0 Hz,
1H), 7.14 (d, J=8.0 Hz, 2H), 7.01–6.98 (m, 2H), 6.30 (d,
J=8.0 Hz, 1H), 5.37 (s, 2H), 5.25 (s, 2H) ppm; 13C NMR
(100 MHz, DMSO-d6): δ=164.18, 161.88, 153.26, 134.59,
133.47, 129.81, 125.45, 124.91, 123.27, 122.61, 117.06,
116.35, 115.40, 92.18, 80.71, 77.68, 57.89 ppm; HRMS:
m/z calculated for C25H18N4O6 ([M+H]+) 471.1226, found
471.1293.
7‑[[1‑[4‑[(4‑Chlorobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8u, C25H18ClN3O4) Brown
solid; yield: 79%; m.p.: 206–208 °C; FT-IR (KBr): V =3396
(O–H str.), 3142 (C–H str. triazole), 3076 (C–H str. aro-
matic ring), 2927 (C–H str., aliphatic), 1719 (C=O str. lac-
tone), 1610, 1513 (C=C str., aromatic ring), 1341 (C–N),
7‑[[1‑[4‑[(3‑Nitrobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8r, C25H18N4O6) Brown solid;
yield: 79%; m.p.: 210–212 °C; FT-IR (KBr): V =3396 (O–H
str.), 3149 (C–H str. triazole), 3064 (C–H str. aromatic ring),
2932 (C–H str., aliphatic), 1720 (C=O str. lactone), 1624,
1512 (C=C str., aromatic ring), 1350 (C–N), 1143 (C–O)
cm−1; 1H NMR (400 MHz, CDCl3): δ=8.30 (d, J=8.0 Hz,
2H), 8.04 (s, 1H, C–H triazole), 7.71–7.63 (m, 4H), 7.43 (d,
J=8.0 Hz, 2H), 7.13 (d, J=8.0 Hz, 1H), 6.99 (d, J=8.0 Hz,
2H), 6.31 (s, 1H), 5.37 (s, 2H), 5.26 (s, 2H) ppm; 13C NMR
(100 MHz, DMSO-d6): δ=164.18, 161.88, 153.26, 134.59,
133.47, 129.81, 125.45, 124.91, 123.27, 122.61, 117.06,
116.35, 115.40, 92.18, 80.71, 77.68, 57.89 ppm; HRMS:
m/z calculated for C25H18N4O6 ([M+H]+) 471.1226, found
471.1215.
1
1122 (C–O) cm−1; H NMR (400 MHz, CDCl3): δ = 8.08
(s, 1H, C–H triazole), 7.84 (d, J = 8.0 Hz, 1H), 7.685 (d,
J=12.0 Hz, 2H), 7.58 (t, 1H), 7.44–7.34 (m, 6H), 7.12 (d,
J=8.0 Hz, 2H), 5.93 (s, 1H), 5.44 (s, 2H), 5.13 (s, 2H) ppm;
13C NMR (100 MHz, CDCl3): δ=160.90, 143.50, 134.71,
132.58, 128.93, 128.77, 123.92, 123.15, 122.43, 121.69,
116.82, 115.91, 115.49, 91.31, 69.69, 62.66 ppm; HRMS:
m/z calculated for C25H18ClN3O4 ([M + H]+) 460.0986,
([M+3]+) 462.0956, found ([M+H]+) 460.0975, ([M+3]+)
462.0947.
7‑[[1‑[4‑[(4‑Bromobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8v, C25H18BrN3O4) Brown
solid; yield: 79%; m.p.: 210–212 °C; FT-IR (KBr):
V = 3395 (O–H str.), 3136 (C–H str. triazole), 3088 (C–H
str. aromatic ring), 2938 (C–H str., aliphatic), 1712 (C=O
str. lactone), 1606, 1514 (C=C str., aromatic ring), 1344
7‑[[1‑[4‑[(4‑Nitrobenzyl)oxy]phenyl]‑1H‑1,2,3‑triazol‑4‑yl]‑
methoxy]‑2H‑chromen‑2‑one (8s, C25H18N4O6) Brown solid;
yield: 79%; m.p.: 210–212 °C; FT-IR (KBr): V =3398 (O–H
str.), 3151 (C–H str. triazole), 3086 (C–H str. aromatic ring),
2945 (C–H str., aliphatic), 1716 (C=O str. lactone), 1614,
1516 (C=C str., aromatic ring), 1348 (C–N), 1124 (C–O)
cm−1; 1H NMR (400 MHz, CDCl3): δ=8.30 (d, J=8.0 Hz,
2H), 8.04 (s, 1H, C–H triazole), 7.71–7.63 (m, 4H), 7.43 (d,
J=8.0 Hz, 2H), 7.13 (d, J=8.0 Hz, 1H), 6.99 (d, J=8.0 Hz,
2H), 6.31 (s, 1H), 5.37 (s, 2H), 5.26 (s, 2H) ppm; 13C NMR
(100 MHz, CDCl3): δ = 164.95, 162.59, 158.58, 154.24,
153.39, 142.07, 132.63, 127.66, 123.97, 123.13, 122.53,
116.84, 115.85, 115.44, 91.29, 69.05, 62.61 ppm; HRMS:
1
(C–N), 1120 (C–O) cm−1; H NMR (400 MHz, DMSO-
d6): δ=8.86 (s, 1H, C–H triazole), 7.97 (d, J=8.0 Hz, 1H),
7.78 (d, J=8.0 Hz, 2H), 7.625 (d, J=4.0 Hz, 1H), 7.575 (d,
J = 4.0 Hz, 2H), 7.405 (d, J = 4.0 Hz, 2H), 7.20–7.16 (m,
3H), 7.03–7.01 (m, 1H), 6.28 (d, J =8.0 Hz, 1H), 5.31 (s,
2H), 5.15 (s, 2H) ppm; 13C NMR (100 MHz, DMSO-d6):
δ=161.58, 160.80, 155.84, 144.84, 143.42, 136.68, 131.96,
130.43, 130.10, 123.73, 122.44, 121.63, 116.35, 113.45,
113.29, 102.13, 69.27, 62.15 ppm; HRMS: m/z calculated for
1 3

1010
C. P. Kaushik, M. Chahal
C25H18BrN3O4 ([M+H]+) 504.0481, ([M+3]+) 506.0460,
found ([M+H]+) 504.0550, ([M+3]+) 506.0530.
drug in methanol and the results of these fndings are pre-
sented in Table 2. Methanol, DPPH solution (0.004 g DPPH
in 100 cm3 methanol) and standard drugs (20–100 µg/cm3)
were used as blank, control and reference, respectively.
Stock solution of the organic compounds was diluted to
diferent concentrations in the range of 20–100 µg/cm3 in
methanol. 2 cm3 of various concentrations of the test com-
pounds (20–100 µg/cm3) in methanol was added to 1 cm3 of
0.004% (w/v) (0.004 g DPPH in 100 cm3 methanol) freshly
prepared DPPH solution. After a 30 min incubation period
at room temperature, the absorbance was measured against
blank at 517 nm (at an absorption maximum of DPPH) with
UV–Visible spectrophotometer and the percentage of scav-
enging activity was calculated. The percentage inhibition
(I%) of the tested compounds was calculated according to
the following equation:
General procedure for in vitro antimalarial activities
The in vitro antimalarial assay was carried out in 96-well
microtitre plates according to the micro assay protocol of
Rieckmann and co-workers [76–81] with minor modifca-
tions. The cultures of P. falciparum strain were maintained
in medium RPMI-1640 supplemented with 25 mM HEPES,
1% D-glucose, 0.23% sodium bicarbonate, and 10% heat
inactivated human serum. The asynchronous parasites of P.
falciparum were synchronized after 5% D-sorbitol treatment
to obtain only the ring stage parasitized cells. For carry-
ing out the assay, the initial ring stage parasitaemia of 0.8
to1.5% at 3% haematocrit in a total volume of 200 mm3
of medium RPMI-1640 was determined by Jaswant Singh
Bhattacharya (JSB) staining to assess the percent parasitae-
mia (rings) and uniformally maintained with 50% RBC (O+).
A stock solution of 5 mg/cm3 of each of the test samples was
prepared in DMSO and subsequent dilutions were prepared
with culture medium. The diluted samples in 20 mm3 vol-
ume were added to the test wells so as to obtain fnal con-
centrations (at fvefold dilutions) ranging from 0.4 to 100 µg/
cm3 in duplicate well containing parasitized cell preparation.
The culture plates were incubated at 37 ºC in a candle jar.
After 36–40 h incubations, thin blood smears from each well
were prepared and stained with JSB stain. The slides were
microscopically observed to record maturation of ring stage
parasites into trophozoites and schizonts in the presence of
diferent concentrations of test agents. The test concentration
which inhibited the complete maturation into schizonts was
recorded as the minimum inhibitory concentrations (MIC).
Quinine was used as the reference drug.
(
)
I% = A0 − A1 ∕A0 × 100,
where A0 is the absorbance of the control reaction and A1
is the absorbance of the test sample. All tests and analyses
were performed in triplicate and the average absorbance was
noted for each concentration. IC50 values were calculated
from the plot of percentage inhibition against concentration
(µg/cm3).
Supplementary Information The online version contains supplemen-
tary material available at https://doi.org/10.1007/s00706-021-02821-8.
Acknowledgements Authors are highly thankful to the Council of Sci-
entifc and Industrial Research (CSIR) for fnancial assistance.
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