Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel 1,2,3-Triazole Tagged 5-[(1H-Indol-3-yl)methylene]pyrimidine-2,4,6(1H,3H,5H)trione Derivatives

Article abstract of DOI:10.1134/S1070363218030313

Novel 5-{(1-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6-(1H,3H,5H)trione derivatives (5a–5k) were synthesized by the click reaction. All compounds 5a–5k were characterized by ¹H and ¹³C NMR, IR a

Full text of DOI:10.1134/S1070363218030313

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 3, pp. 587–595. © Pleiades Publishing, Ltd., 2018.
Synthesis, Biological Evaluation,
and Molecular Docking Studies of Novel 1,2,3-Triazole Tagged
5-[(1H-Indol-3-yl)methylene]pyrimidine-2,4,6(1H,3H,5H)trione
Derivatives1
Ashok Kumara,d*, B. Sathish Kumarb, E. Sreenivasc, and T. Subbaiahd**
a Department of Chemistry, Sreenidhi Institute of Science and Technology, Yamnampet, Ghatkesar,
Hyderabad, Telangana, 501301 India
*e-mail: mailme2ashokkumar@gmail.com
b Department of Chemistry, Osmania University, Hyderabad, Telangana, 500007 India
c Bioinformatics Division, Averin Biotech Pvt. Ltd. Windsorplaza, Nallakunta, Hyderabad, Telangana, 500044 India
d Department of Chemistry, Koneru Lakshmaiah Deemed to be University, Green Fields, Vaddeswaram,
Guntur (Dist), Andhra Pradesh, 522502 India
**e-mail: tsubbaiah@yahoo.com
Received February 8, 2018
Abstract—Novel 5-{(1-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6-
(1H,3H,5H)trione derivatives (5a–5k) were synthesized by the click reaction. All compounds 5a–5k were
1
characterized by H and 13C NMR, IR and Mass spectra and evaluated for their in vitro anticancer activity
against cervical cancer cell lines. Among all, compound 5e (IC50 = 6.76 μM), shown high inhibitory activity.
Docking analysis of all the compounds with the Lipid kinase PI3K-α revealed that the compound 5e fitted well
in the active site pocket, showing the best docking score (LibDock) of 123.274.
Keywords: 1,2,3-triazole, indole, click reaction
DOI: 10.1134/S1070363218030313
, cervical cancer, molecular docking
INTRODUCTION
ceuticals properties such as anticancer [19, 20], anti-
microbial [21, 22], antiviral [23], anti-inflammatory
[24], anti-tubercular [25], anti-HIV [26], and
anticonvulsant [27] along with significant insecticidal
[28], anti-phyto-pathogenic [29] and antidiabetic [39]
activities. In view of the above observations, it was
important to synthesize a new functionalized barbituric
acid, indole and 1,2,3-triazole hybrid derivatives. All
newly synthesized compounds were evaluated for their
in vitro anticancer activity. Molecular docking studies
were performed for those. Some of the known
barbituric acid, indole and 1,2,3-triazole derivatives
were reported to be pharmacologically active (Fig. 1).
One of the most fruitful paradigms for discovery of
new bioactive chemical entities is starting with
established structural cores, known to be part of other
bioactive molecules [1]. Barbiturates exhibit a broad
range of biological activities, including sedative [2],
anticancer [3], antibacterial [4], antioxidant [5],
hypnotic [6], anti-convulsant [7], immuno-modulating
[8], radio-sensitizing [9], and gelatinase inhibiting
[10]. Indole derivatives constitute an important class of
heterocyclic compounds with a wide range of
pharmacological properties including anticancer [11],
antimicrobial [12], anti-malarial [13], anti-tubercular
[14], anti-inflammatory [15], antiviral [16], antioxidant
[17] activities, and HIV inhibiting [18]. Following the
same approach, 1,4-disubstituted 1,2,3-triazoles
display a number of agrochemical and pharma-
RESULTS AND DISCUSSION
Synthesis. All title compounds were synthesized in
three consecutive steps (Scheme 1). In the first step,
reaction between 1H-indole-3-carbaldehyde (1) and
propargyl-bromide in the presence of K2CO3 in dry
DMF lasted for 1 h upon stirred at 80°C with
1 The text was submitted by the authors in English.
587

588
ASHOK KUMAR et al.
COOH
NH2
O
O
NH2
HO
NH
NH
N
O
N
H
O
O
N
H
O
N
H
H
3, Cerotonine
4, Tryptophan
2, Phenobarbital
1, Barbital
HN
N
COOH
O
S
O
O
N
S
N
N
O
4
N
OH
N
N
S
N
O
H
COOH
5, Tazobactum
Fig. 1. Selected examples of pharmacologically important barbituric acid, indole, and 1,2,3-triazole derivatives.
H2N
6, Cefatrizine
formation of 1-(prop-2-yn-1-yl)-1H-indole-3-carbal-
dehyde (2). In the second step, inter-mediate 2 was
subjected to the Knoevenagel condensation with
pyrimidine-2,4,6(1H,3H,5H)trione (3) upon refluxing
in the presence of piperidine as a catalyst in ethanol for
4 h leading to 5-{[1-(prop-2-yn-1-yl)-1H-indol-3-yl]-
methylene}pyrimidine-2,4,6(1H,3H,5H)trione inter-
mediate (4). In the final step intermediate 4 was
introduced in cycloaddition with various substituted
aromatic azides/substituted benzyl azides under the
click reaction conditions in the presence of Cu(I) as a
catalyst in dry THF for 12 h to give the corresponding
derivatives of 5-{(1-[(1-phenyl-1H-1,2,3-triazol-4-yl)-
methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6-
(1H,3H,5H)trione (5a–5k) in quantitative yield.
cell line). The results of cytotoxic tests were expressed
in terms of IC50 (µM), and doxorubicin was used as a
positive control (Table 2). The structural diversity of
the derivatives was achieved by varying substituents at
the third position of the triazole ring. According to the
accumulated data (Table 2), most of compounds were
moderately active but some compounds 5b, 5d, 5e, 5g
demonstrated high inhibition against HeLa (IC50
27.09 µM), (IC50 36.08 µM), (IC50 6.76 µM), and (IC50
33.46 µM) cell line respectively.
Molecular docking. Molecular interactions of the
synthesized compounds were studied by means of
molecular docking using Discovery Studio 2.1
software. Crystallographic data of Lipid kinase PI3K-α
(PDB: 3ZIM) were retrieved from the Protein Data
Bank. Retrieved crystal structure of Lipid kinase PI3K-
α was cleaned and hydrogen atoms were added. All
heteroatoms were removed before docking study.
The structures of all derivatives 5a–5k (Table 1)
1
were confirmed by H and 13C NMR, IR, and ESI-MS
spectra. 1H NMR spectra of compounds 5a–5k
exposed singlets in the ranges of 5.58–5.86 ppm and
8.63–9.70 ppm that were attributed to the methylene
protons attached to nitrogen atom of indole ring and
proton of 1,2,3-triazole ring respectively, whereas the
corresponding carbon resonances in the 13C NMR
spectra were observed at 41.2–42.3 and 121.9–123.2 ppm,
respectively. The other protons and carbons resonated
at the expected regions.
Docking study of the title derivatives 5a–5k with
lipid kinase PI3K-α revealed the high docking scores
(LibDock) and binding affinities, in the range of
111.171–123.274, as compared to Doxorubicin 125.50.
In the active site pocket of Lipid kinase PI3K-α target
protein interacting residues were Tyr836, Glu849,
Val851, Val850, Ile848, Ile800, Asp810, Asp933,
Met772, Ser854, Gln859, Cys862, Met858, and
Lys802. Among all compounds, the derivative 5e fitted
well in the active site pocket of Lipid kinase PI3K-α,
showing the best docking score (LibDock) of 123.274
(Table 3, Fig. 2).
Anti-cancer activity. The in vitro cytotoxic activity
of the synthesized compounds was evaluated using
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay on the HeLa (cervical cancer
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SYNTHESIS, BIOLOGICAL EVALUATION, AND MOLECULAR DOCKING STUDIES
589
Scheme 1. Synthesis of 5-{(1-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6(1H,3H,5H)-
trione derivatives (5a–5k).
CHO
CHO
K2CO3, DMF
Br
+
2 h, 80οC
N
N
H
2
1
Step 1. Synthesis of 1-(prop-2-yn-1-yl)-1H-indole-3-carbaldehyde (2).
O
CHO
O
O
HN
NH
NH
piperidene
O
O
N
etanol, 4 h, reflux
O
N
H
N
2
4
3
Step 2. Synthesis of 5-{[1-(prop-2-yn-1-yl)-1H-indol-3-yl]methylene}pyrimidine-2,4,6(1H,3H,5H)trione (4).
O
O
HN
HN
Ar−N3, dry THF, CuI
room temperature, 10−12 h
O
O
N
N
O
N
H
O
N
H
Ar
N
N N
4
5a−5k
Step 3. Synthesis of 1,2,3-triazole derivatives 5a–5k.
EXPERIMENTAL
dissolved in 10 mL of dry dimethyl formamide. Later,
propargylbromide (23 mmol) was added slowly upon
stirring. The reaction mixture was stirred at 80°C
temperature for 2 h and then extracted with ethyl
acetate to afford crude N-propargyl benzaldehyde. Puri-
fication of the crude residue by column chromato-
graphy using 15% ethyl acetate in hexane as an eluent
led to isolation of pure compound 2.
Melting points of all compounds were determined
on a Casia-Siamia (VMP-AM) melting point ap-
paratus. IR spectra were recorded on a Perkin–Elmer
FT-IR spectrophotometer for KBr discs. NMR spectra
were measured for DMSO-d6 solutions on a Bruker
Avance 400 MHz using TMS as an internal standard.
Electron impact (EI) and chemical ionization mass
spectra were recorded on a VG Micro mass model
7070H instrument. All reactions were monitored by
TLC on precoated Merck silica gel plates and spots
were visualized under UV light. Column chromato-
graphy was carried out on Silica gel, 100–200 mesh
(Merck).
Synthesis of 5-[(1-(prop-2-yn-1-yl)-1H-indol-3-
yl]methylene)pyrimidine-2,4,6(1H,3H,5H)trione.
Pyrimidine-2,4,6(1H,3H,5H)trione 3 (33 mmol) was
dissolved in ethanol (10 mL) and catalytic amount of
piperidine was added. To this mixture 1-(prop-2-yn-1-
yl)-1H-indole-3-carbaldehyde 2 (33 mmol) was added.
The reaction mixture was refluxed for 4 h. The solvent
was removed under reduced pressure and the residue
was diluted by distilled water and extracted thrice with
dichloromethane. The combined organic layers were
Synthesis of 1-(prop-2-yn-1-yl)-1H-indole-3-carbal-
dehyde (2). 1H-Indole-3-carbaldehyde 1 (23 mmol)
along with potassium carbonate (25 mmol) were
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ASHOK KUMAR et al.
Table 1. 5-{(1-[(1-Phenyl-1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6(1H,3H,5H)trione
derivatives (5a–5k)
Comp. no.
Ar
Product
O
HN
5a
N
NO2
N
N
O
O
O
O
N
O
NO2
H
N
N
N
N
O
Cl
Cl
Cl
Cl
HN
5b
5c
5d
5e
5f
N
N
N
N
N
N
O
H
O
HN
N
N
N
O
H
O
Br
HN
Br
N
N
N
O
H
O
O
O
H
HN
COOH
N
N
N
N
O
O
N
O
H
N
N
O
F
HN
F
N
N
N
O
H
O
HN
5g
5h
N
N
N
N
O
O
N
O
H
N
N
O
HN
N
N
N
O
H
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SYNTHESIS, BIOLOGICAL EVALUATION, AND MOLECULAR DOCKING STUDIES
Table 1. (Contd.)
Comp. no.
591
Ar
Product
CN
O
NC
HN
5i
5j
N
N
N
O
O
O
N
O
H
N
N
N
Cl
O
Cl
HN
N
N
N
N
N
O
H
O
HN
5k
N
N
N
Cl
O
H
Cl
Table 2. Anticancer activity of the compounds 5a–5k
HeLa cervical cancer cell line
HeLa cervical cancer cell line
IC50, µM
Compound
IC50, µM
Compound
5a
5b
5c
5d
5e
5f
57.90
27.09
91.64
36.08
6.76
5g
5h
5i
33.460
54.560
62.900
66.210
70.270
4.719
5j
5k
49.81
Doxorubicin
dried over anhydrous Na2SO4 and concentrated giving
the product 4, which was purified by column
chromatography using ethyl acetate in hexane.
thrice with ethyl acetate. The combined organic layers
were dried over anhydrous Na2SO4 and concentrated to
give the product which was purified by column
chromatography using ethyl acetate in hexane.
Synthesis of 5-{(1-[(1-phenyl-1H-1,2,3-triazol-4-
yl)methyl]-1H-indol-3-yl)methylene}pyrimidine-
2,4,6(1H,3H,5H)trione derivatives (5a–5k). The
intermediate, 5-{[1-(prop-2-yn-1-yl)-1H-indol-3-yl]me-
thylene}pyrimidine-2,4,6(1H,3H,5H)trione 4 (3.0 mmol),
was dissolved in dry THF (10 mL) and catalytic
amount of CuI was added. To this, substituted
aromatic azide/benzyl azide (3.0 mmol) in dry THF
were added slowly upon stirring at room temperature
under nitrogen atmosphere. After 12 h of stirring the
solvent was removed under reduced pressure, the
residue was diluted by distilled water and extracted
5-{(1-[(1-(2-Methyl-3-nitrobenzyl)-1H-1,2,3-
triazol-4-yl)methyl]-1H-indol-3-yl)methylene}
pyrimidine-2,4,6(1H,3H,5H)trione (5a). Yield 90%,
mp 243–245°C. IR spectrum, ν, cm–1: 3093, 2947,
1
1738, 1669, 1554, 1439. H NMR spectrum, δ, ppm:
2.13 s (3H). 5.86 s (2H), 7.43–7.35 m (2H), 7.66 t (J =
8.1 Hz, 1H), 7.81–7.89 m (2H), 7.92 d.d (J = 6.2,
2.7 Hz, 1H), 8.16 d.d (J = 8.2, 1.0 Hz, 1H), 8.68 s
(1H), 8.78 s (1H), 9.67 s (1H), 11.10 s (1H), 11.17 s
(1H). 13C NMR spectrum, δC, ppm: 13.86, 41.94,
109.10, 110.73, 112.06, 117.89, 123.10, 123.79, 125.67,
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ASHOK KUMAR et al.
Table 3. Docking score (LibDock) and ligand interaction data for the compounds 5a–5k
H-
Interacting atoms
Distance
H-
Distance
Interacting atoms
5a 118.579 –44.601 A:TYR836:HH-5a:O9 2.407000
A:LYS802:HZ1-5a:O11 1.785000
5a:H37-A:ASP933:OD1 2.446000
5a:H37-A:ASP933:OD2 1.981000
A:GLN859:HN-5a:O34 2.405000
A:GLN859:HN-5a:O35 1.812000
A:MET858:HN1-5a:O35 1.313000
5g 116.002 –53.280 A:LYS802:HZ1-5g:O11 1.544000
A:TYR836:HH-5g:O10 1.867000
5g:H34-A:ASP810:OD1 1.975000
5g:H34-A:ASP810:OD2 2.443000
5b 119.425 –41.523 A:GLN859:HN-5b:O34 1.756000
A:GLN859:HN-5b:O35 2.469000
A:LYS802:HZ1-5b:O11 1.512000
A:TYR836:HH-5b:O10 1.848000
5b:H37-A:ASP810:OD1 2.026000
5b:H37-A:ASP810:OD2 2.456000
A:MET858:HN1-5b:O34 1.477000
5h 112.821 –50.387 A:VAL851:HN-5h:N22 2.494000
A:VAL851:HN-5h:N23 2.117000
5h:H34-A:ASP810:OD1 2.092000
A:TYR836:HH-5h:O11 1.911000
A:TYR836:HH-5h:N8 2.345000
A:ASP933:HN-5h:N8 2.477000
5c 117.203 –55.506 A:LYS802:HZ1-5c:N6 1.466000
5i 111.171 –44.647 A:VAL851:HN-5i:N22 2.494000
A:VAL851:HN-5i:N23 2.247000
A:LYS802:HZ1-5c:O10 2.121000
A:LYS802:HZ3-5c:N6 2.277000
A:MET858:HN1-5i:O11 1.854000
A:VAL851:HN-5c:N22 2.165000
A:GLN859:HN-5i:N6 2.260000
5c:H34-A:ASP933:OD1 2.381000
A:GLN859:HN-5i:O11 2.290000
5c:H34-A:ASP933:OD2 2.451000
5i:H36-A:MET858:N 1.872000
5d 116.91 –53.473 5d:H34-A:ASP810:OD1 2.431000
5j 119.187 –49.887 A:VAL851:HN-5j:N22 2.496000
5d:H34-A:ASP810:OD2 2.494000
A:VAL851:HN-5j:N23 2.250000
A:LYS802:HZ1-5d:O11 1.562000
A:MET858:HN1-5j:O11 1.858000
A:TYR836:HH-5d:O10 2.455000
A:GLN859:HN-5j:N6 2.257000
A:GLN859:HN-5d:Br32 2.390000
A:GLN859:HN-5j:O11 2.281000
5j:H35-A:MET858:N 1.877000
5e 123.274 –56.057 A:LYS802:HZ1-5e:O11 1.363000
A:TYR836:HH-5e:O10 1.620000
A:GLN859:HN-5e:O33 2.090000
2.298000
5k 119.112 –54.839 A:LYS802:HZ1-5k:O10 1.815000
A:TYR836:HH-5k:O11 1.639000
A:ASP933:HN-5k:N8 2.417000
A:ASP933:HN-5k:O11 2.297000
A:GLN859:HN-5e:O34 2.404000
A:ASP933:HN-5e:O10 2.118000
5e:H36-A:ASP810:OD1 2.420000
5e:H36-A:ASP810:OD2 1.932000
A:MET858:HN1-5e:O33
5k:H35-A:TYR836:OH 2.452000
126.54, 127.90, 128.41, 129.80, 131.07, 136.34, 137.44,
141.71, 142.10, 142.87, 150.40, 150.60, 163.10, 164.42.
ESI-MS: m/z: 486 [M + 1] observed for C24H19N7O5.
m (2H), 8.24 s (1H), 8.68 s (1H), 9.04 s (1H), 9.70 s
(1H), 11.11 s (1H), 11.18 s (1H). 13C NMR spectrum,
δC, ppm: 41.53, 110.02, 114.57, 115.22, 115.87, 120.20,
121.93, 123.40, 125.50, 129.90, 131.15, 131.23, 131.81,
132.34, 135.90, 137.36, 143.50, 150.17, 154.73, 161.91,
163.84. ESI-MS: m/z: 495 [M + 1] observed for
C23H16Cl2N6O3.
5-{(1-([1-(2,3-Dichlorobenzyl)-1H-1,2,3-triazol-4-
yl)methyl]-1H-indol-3-yl)methylene}pyrimidine-
2,4,6(1H,3H,5H)trione (5b). Yield 85%, mp 220–
222°C. IR spectrum, ν, cm–1: 3087, 2826, 1740, 1668,
1
1544, 1435. H NMR spectrum, δ, ppm: 5.85 s (2H),
5-{(1-([1-(4-Methylbenzyl)-1H-1,2,3-triazol-4-yl)-
methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6-
7.25–7.42 m (3H), 7.85 d (J = 9.0 Hz, 1H), 7.89–7.94
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SYNTHESIS, BIOLOGICAL EVALUATION, AND MOLECULAR DOCKING STUDIES
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Fig. 2. Receptor-ligand hydrogen bonds and bumps of compound 5e with the active site residues of α-lipid kinase PI3K (PDB:
3ZIM).
(1H,3H,5H)trione (5c). Yield 86%, mp 230–231°C.
IR spectrum, ν, cm–1: 3090, 2971, 1723, 1677, 1588,
1452. H NMR spectrum, δ, ppm: 5.82 s (2H), 2.36 s
(3H), 7.31–7.43 m (4H), 7.75 d (J = 8.3 Hz, 2H), 7.89
d (J = 8.9 Hz, 2H), 8.68 s (1H), 8.92 s (1H), 9.69 s
(1H), 11.10 s (1H), 11.17 s (1H). 13C NMR spectrum,
δC, ppm: 14.13, 42.30, 109.03, 112.32, 115.56, 117.01,
120.07, 123.26, 123.57, 125.68, 126.31, 127.10, 130.24,
131.23, 134.24, 138.48, 142.94, 150.14, 161.30, 163.91.
ESI-MS: m/z: 441 [M + 1] observed for C24H20N6O3.
11.10 s (1H), 11.17 s (1H), 13.27 s (1H). 13C NMR
spectrum, δC, ppm: 41.42, 109.17, 110.70, 111.28,
117.49, 121.04, 122.30, 122.62, 123.65, 129.81, 136.26,
136.80, 140.74, 141.79, 143.70, 150.37, 163.12, 164.40,
184.78. ESI-MS: m/z: 471 [M + 1] observed for
C24H18N6O5.
1
5-{(1-[(1-{4-Fluorobenzyl}-1H-1,2,3-triazol-4-yl)-
methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6-
(1H,3H,5H)trione (5f). Yield 81%, mp 218–220°C.
IR spectrum, ν, cm–1: 3049, 2971, 1735, 1663, 1546,
1
5-{(1-([1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl)-
methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6-
(1H,3H,5H)trione (5d). Yield 80%, mp 208-210°C.
IR spectrum, ν, cm–1: 3087, 2826, 1741, 1668, 1540,
1457. H NMR spectrum, δ, ppm: 5.84 s (2H), 7.28–
7.46 m (4H), 7.73–7.92 m (4H), 8.68 s (1H), 8.95 s
(1H), 9.70 s (1H), 11.11 s (1H), 11.18 s (1H). 13C NMR
spectrum, δC, ppm: 41.83, 109.91, 112.34, 114.93,
115.59, 122.56, 122.65, 123.63, 124.56, 125.71, 130.01,
131.19, 133.06, 136.08, 136.91, 143.11, 155.23, 162.30,
162.80, 163.91. ESI-MS: m/z: 445 [M + 1] observed for
C23H17FN6O3.
1
1435. H NMR spectrum, δ, ppm: 5.84 s (2H), 7.23–
7.42 m (4H), 7.69–7.95 m (4H), 8.46 s (1H), 8.94 s
(1H), 9.70 s (1H), 11.11 s (1H), 11.19 s (1H). 13C NMR
spectrum, δC, ppm: 42.06, 109.90, 110.83, 111.03,
117.54, 121.13, 122.71, 123.65, 124.82, 130.02, 136.51,
136.82, 139.91, 140.70, 142.51, 143.51, 150.01, 153.40,
160.93, 162.06. ESI-MS: m/z: 505 [M + 1] observed for
C23H17BrN6O3.
5-{(1-[(1-{2-Methylbenzyl}-1H-1,2,3-triazol-4-yl)-
methyl]-1H-indol-3-yl)methylene}pyrimidine-2,4,6-
(1H,3H,5H)trione (5g). Yield 80%, mp 212–215°C.
1H NMR spectrum, δ, ppm: 2.32 s (3H), 5.79 s (2H),
7.35 d.d (J = 9.5, 6.3 Hz, 4H), 7.70–7.90 m (4H), 8.68
s (1H), 8.90 s (1H), 9.68 s (1H), 11.07 s (1H), 11.12 s
(1H). 13C NMR spectrum, δC, ppm: 13.80, 41.93,
109.15, 110.80, 112.10, 117.90, 120.93, 123.06, 123.81,
125.60, 126.50, 127.91, 128.42, 129.31, 131.01, 136.30,
137.40, 141.93, 150.31, 163.15, 164.40. ESI-MS: m/z:
441 [M + 1] observed for C24H20N6O3.
4-{(4-[(3-{(2,4,6-Trioxotetrahydropyrimidin-
5(2H)-ylidene)methyl}-1H-indol-1-yl)methyl]-1H-
1,2,3-triazol-1-yl)methyl}benzoic acid (5e). Yield
92%, mp 251–252°C. IR spectrum, ν, cm–1: 3104,
1
3020, 2930, 1721, 1703, 1675, 1541, 1445. H NMR
spectrum, δ, ppm: 5.86 s (2H), 7.19–7.46 m (4H), 7.61–
8.04 m (4H), 8.46 s (1H), 8.68 s (1H), 9.70 s (1H),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 3 2018

594
ASHOK KUMAR et al.
5-{(1-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]-
5k have been synthesized, and their in vitro anticancer
activity against HeLa (cervical cancer cell line) was
tested. The structures of all newly synthesized
1H-indol-3-yl)methylene}pyrimidine-2,4,6(1H,3H,5H)-
trione (5h). Yield 88%, mp 225–227°C. IR spectrum,
ν, cm–1: 3087, 2826, 1740, 1668, 1544, 1435. 1H NMR
spectrum, δ, ppm: 5.58 s (2H), 5.72 s (2H), 7.24–7.47
m (7H), 7.54–7.95 m (2H), 8.29 s (1H), 8.66 s (1H),
9.63 s (1H), 11.10 s (1H), 11.17 s (1H). 13C NMR
spectrum, δC, ppm: 42.92, 52.61, 109.22, 110.64,
112.02, 117.91, 123.09, 123.80, 125.86, 127.17, 128.06,
130.77, 133.27, 136.36, 137.54, 141.89, 142.90, 150.36,
163.11, 164.37. ESI-MS: m/z: 427 [M + 1] observed for
C23H18N6O3.
1
derivatives were confirmed by H and 13C NMR, IR,
and ESI-MS spectra. Among the tested compounds,
the compound 5e exhibited selective activity against
cervical cancer cell line with IC50 value of 6.76 µM.
Molecular docking of the synthesized derivatives with
human Lipid kinase PI3K-α revealed the LibDock
score in the range of 111.171–123.274.
ACKNOWLEDGMENTS
2-{(4-[(3-{(2,4,6-Trioxotetrahydropyrimidin-
5(2H)-ylidene)methyl}-1H-indol-1-yl)methyl]-1H-
1,2,3-triazol-1-yl)methyl}benzonitrile (5i). Yield
85%, mp 231–232°C. IR spectrum, ν, cm–1: 3079, 2229,
The authors are grateful to the Department of
Chemistry, Sreenidhi Institute of Science and
Technology, Hyderabad for providing Laboratory
facilities and one of the author, A. Kumar, is grateful
to Department of Chemistry, Koneru Lakshmaiah
University, Andhra Pradesh for the support of this
work.
1
1740, 1701, 1672, 1549, 1426. H NMR spectrum, δ,
ppm: 5.75 s (2H), 5.81 s (2H), 7.32 d (J = 7.8 Hz, 1H),
7.37 m (2H), 7.55 t (J = 7.5 Hz, 1H), 7.68–7.74 m
(1H), 7.78–7.84 m (1H), 7.91 d (J = 6.9 Hz, 2H), 8.36
s (1H), 8.66 s (1H), 9.63 s (1H), 11.09 s (1H), 11.17 s
(1H). ESI-MS: m/z: 452 [M + 1] observed for C24H17N7O3.
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