Vol. 32, No. 4 (2020)
Synthesis, Characterization, in silico and in vitro Evaluations of Symmetrical 1,3-Diketones 857
7.41 (m, 1H), 4.26 (s, 2H), 2.18 (s, 3H); IR (KBr, νmax, cm–1):
3441, 3052, 2932, 1704, 1603, 1514, 1425, 1155, 1015, 796;
HRMS (ESI-TOF) of [M+Na]+ calcd. for C13H12O+Na+.
207.0780; found, 207.07601.
(1H-Benzo[d][1,2,3]triazol-1-yl)(5-iodo-2-methylphenyl)-
methanone (3b): It was synthesized according to general proce-
dure-D. The residue was purified by column chromatography
using 2 % of ethylacetate in hexanes to afford compound 3b
as a colourless solid;Yield: 70 %; 1H NMR (500 MHz, DMSO-
d6, δ ppm): δ 8.34 (d, J = 8.50 Hz, 1H), 8.30 (d, J = 8.00 Hz,
1H), 8.12 (s, 1H), 7.92 (d, J = 8.00 Hz, 1H), 7.80 (t, J = 8.00
Hz, 1H), 7.68 (t, J = 8.00 Hz, 1H), 7.26 (d, J = 8.00 Hz, 1H),
2.30 (s, 3H); HRMS (ESI-TOF) of [M+Na]+ calcd. for
C14H10IN3O +Na+. 385.9761; found, 385.97557.
(1H-Benzo[d][1,2,3]triazol-1-yl)(1-tosylpiperidin-3-yl)
methanone (3c): It was synthesized according to general pro-
cedure-D. The residue was purified by column chromatography
using 25 % of ethylacetate in hexanes to afford compound 3c
as a colourless solid;Yield: 61 %; 1H NMR (500 MHz, DMSO-
d6, δ ppm): δ 8.27 (d, J = 8.00 Hz, 1H), 8.20 (d, J = 8.50 Hz,
1H), 7.79 (t, J = 7.50 Hz, 1H), 7.66 (d, J = 8.00 Hz, 2H), 7.63
(t, J = 7.00 Hz, 1H), 7.46 (d, J = 8.00 Hz, 2H), 4.02 (d, J =
10.50 Hz, 2H), 3.57 (d, J = 12.00 Hz, 1H), 2.70 (t, J = 11.00
Hz, 1H), 2.48-2.51 (m, 2H), 2.42-2.46 (m, 3H), 2.10-2.12 (m,
1H), 1.85-1.86 (m, 1H), 1.62-1.64 (m, 1H); HRMS (ESI-TOF)
of [M+Na]+ calcd. for C19H20N4O3S +Na+. 407.1148; found,
407.11413.
2952, 1575, 1513, 1411, 1350, 1197, 1146, 1075, 891, 784, 626;
HRMS (ESI-TOF) of [M]+ calcd. for C17H14I2O2. 503.9083;
found, 503.9101.
3-Hydroxy-1,3-bis(1-tosylpiperidin-3-yl)prop-2-en-1-
one (5c): It was synthesized according to general procedure-
E. The residue was purified by column chromatography using
24 % of ethylacetate in hexanes to afford compound 5c as
colourless solid;Yield 72 %; reaction time: 18 h, m.p.: 126 °C;
1H NMR (400 MHz, CDCl3, δ ppm): δ 7.63 (d, J = 8.00 Hz,
4H), 7.32 (d, J = 8.00 Hz, 4H), 5.58 (s, 1H), 3.64-3.67 (m,
4H), 2.51-2.53 (m, 2H), 2.39 (s, 6H), 2.26-2.29 (m, 2H), 1.70-
1.76 (m, 4H), 1.64-1.61 (m, 3H), 1.38-1.40 (m, 3H); 13C NMR
(100 MHz, CDCl3, δ ppm): 193.9, 193.2, 143.5, 132.8, 132.8,
129.6, 127.5, 97.7, 48.06, 48.01, 46.3, 44.2, 44.1, 26.99, 26.97,
24.1, 21.6; IR (KBr, νmax, cm–1): 3474, 3067, 2954, 2852, 1596,
1442, 1331, 1147, 1086, 841; HRMS (ESI-TOF) of [M+Na]+
calcd. for C27H34N2O6S2+Na+. 569.1750; found, 569.17539.
4-Hydroxy-1,5-di(naphthalene-1-yl)pent-3-en-2-one (5d):
This compound was already reported [21]. It was synthesized
according to general procedure-E. The residue was purified by
column chromatography using 0.5 % of ethylacetate in hexanes
to afford compound 5d as a pale yellow solid; Yield 75 %;
reaction time: 3 h, m.p.: 80 °C; 1H NMR (500 MHz, DMSO-
d6, δ ppm): δ 7.93-7.94 (m, 2H), 7.85-7.86 (m, 4H), 7.52-7.52
(m, 4H), 7.46-7.48 (m, 2H), 7.40-7.41 (m, 2H), 4.26 (s, 4H),
3.36 (s, 2H); IR (KBr, νmax, cm–1): 3464, 3046, 2924, 1586,
1504, 1403, 954, 780; HRMS (ESI-TOF) of [M+H]+ calcd.
for C25H20O2 + H+. 353.1536; found, 353.15420.
Molecular docking studies: The docking studies have
been carried out using docking programAuto dock tool (ADT)
version 1.5.6 and Auto dock version 4.2.6 [22]. The 3D X-ray
crystal structure of PTK6 otherwise known as BrK (PDB ID:
6CZ3) and COX2 (PDB ID: 3LN1) were retrieved from PDB
graphic PDB receptors were initially processed in Discovery
studio visualizer to remove the water molecules, heteroatoms,
miscellaneous molecules and ligands attached to it. All the
structures of compounds were saved as PDB file format for
input to ADT. Using ADT, a grid box was constructed around
the binding site of receptor protein and pdbqt files of ligands.
The Auto dock calculation such as binding score (kcal/mol)
and inhibition constant (ki) values were calculated from the
best docked poses of ligands (5a-d) at the active sites of PTK6
and COX2.Binding mode and interaction of the compounds
with amino acid residues in the active sites of the protein was
analyzed using Discovery studio visualizer.
(1H-Benzo[d][1,2,3]triazol-1-yl)(1-tosylpiperidin-3-
yl)methanone (3d): It was synthesized according to general
procedure-D. The residue was purified by column chromato-
graphy using 1.5 % of ethylacetate in hexanes to afford com-
1
pound 3d as a colourless solid; Yield: 71 %; H NMR (400
MHz, CDCl3, δ ppm): δ 8.21-8.25 (m, 1H), 8.09-8.11 (m, 2H),
7.83-7.85 (m, 2H), 7.60-7.61 (m, 2H), 7.42-7.42 (m, 4H), 5.20
(s, 2H); HRMS (ESI-TOF) of [M+Na]+ calcd. for C18H13N3O
+Na+. 310.0951; found, 310.09570.
3-Hydroxy-1,3-bis(1-tosylpyrrolidin-2-yl)prop-2-en-1-
one (5a): It was synthesized according to general procedure-
E. The residue was purified by column chromatography using
25 % of ethylacetate in hexanes to afford compound 5a as a
pale yellow solid;Yield 70 %; reaction time: 16 h, m.p.: 157 °C;
1H NMR (400 MHz, CDCl3, δ ppm): δ 7.79 (d, J = 8.00 Hz,
4H), 7.38 (d, J = 8.00 Hz, 4H), 6.36 (s, 1H), 4.19 (q, J = 13.20
Hz, 2H), 3.60-3.62 (m, 2H), 3.27-3.29 (m, 2H), 2.48 (s, 6H),
2.01-2.02 (m, 2H), 1.91-1.92 (m, 4H), 1.69-1.70 (m, 2H); IR
(KBr, νmax, cm–1): 3440, 3051, 2981, 2871, 1923, 1603, 1433,
1343, 1153, 1083, 1013, 804; HRMS (ESI-TOF) of [M+Na]+
calcd. for C25H30N2O6S2 +Na+. 541.1437; found, 541.4308.
3-Hydroxy-1,3-bis(5-iodo-2-methylphenyl)prop-2-en-
1-one (5b): It was synthesized according to general procedure-
E. The residue was purified by column chromatography using
0.1 % of ethylacetate in hexanes to afford compound 5b as
colourless solid;Yield 82 %; reaction time: 3 h, m.p.: 145 °C;
1H NMR (500 MHz, DMSO-d6, δ ppm): δ 7.98 (s, 2H), 7.79
(d, J = 7.50 Hz, 2H), 7.15 (d, J = 8.00 Hz, 2H), 6.53 (s, 1H),
2.52 (s, 6H); 13C NMR (125 MHz, DMSO-d6, δ ppm): 200.6,
187.4, 151.1, 140.1, 139.5, 137.4, 137.1, 136.5, 136.3, 133.7,
133.4, 101.2, 91.1, 57.8, 19.9; IR (KBr, νmax, cm–1): 3452, 3055,
Cytotoxicity studies on breast cancer cell line-MTT
assay: The MDAMB231 cells were plated separately using
96 well plates with the concentration of 1 × 104 cells/well in
DMEM media with 1X antibiotic antimycotic solution and
10 % fetal bovine serum (Himedia, India) in CO2 incubator at
37 °C with 5 % CO2. The cells were washed with 200 µL of
1X PBS and incubated for 24 h with various concentrations
(0.01-15 µg/mL) of the compound 5d, which exhibited the
higher binding affinity with PTK6, in silico studies and the
standard, Doxorubicin (in serum free media). The medium
was aspirated from cells at the end of the treatment period. 0.5
mg/mL MTT prepared in 1X PBS was added and incubated at