1322 Navudu et al.
Asian J. Chem.
J = 7.4 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.53 (s, 1H), 7.61
(d, J = 7.3 Hz, 1H), 8.10 (s, 1H): 13C NMR (100 MHz, DMSO-
d6): δ 56.60, 61.03, 112.33, 114.86, 117.65, 118.93, 124.83,
127.66, 127.97, 133.79, 135.0, 147.77, 156.87, 163.86, ESI-MS:
m/z 280 (M+H). Calculated mass for the formula C16H13N3O2
-279. Calculated C, 68.81, H, 4.69, N, 15.05 %; Found: C,
68.79, H, 4.70, N, 15.08 %.
7.04 (d, J = 8.31 Hz, 2H), 7.05 (s, 1H), 7.34 (m, 2H), 7.53 (t,
J = 6.88 Hz, 1H), 7.67 (d, J = 7.18 Hz, 1H), 7.74 (d, J = 7.90
Hz, 2H), 7.95 (d, J = 7.42 Hz, 2H), 8.28 (s, 1H), 8.85 (s, 1H):
13C NMR (100 MHz, DMSO-d6): δ 55.50, 60.67, 114.24,
115.02, 115.98, 118.12, 118.53, 120.30, 125.17, 126.75,
127.95, 129.70, 129.96, 133.57, 139.73, 149.04, 151.07,
159.65, 164.51. ESI-MS: m/z 397 (M+H). Calculated mass
for the formula C24H20N4O2 -398 Calculated C, 72.71, H, 5.08,
N, 14.13 %; Found: C, 72.68, H, 5.12, N, 14.09 %.
2,3-Dihydro-2-(3-ethoxy-4-methoxyphenyl)quinazolin-
4(1H)-one (3b): This compound was obtained as a light yellow
1
solid; m.p. 182-184 °C. H NMR (400 MHz, DMSO-d6): δ
Anticancer activity: The compounds were tested onA549
(Human lung carcinoma cell line) cells using 3-(4,5-dimethyl-
thiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) cell
proliferation assay [23]. A549 cell line was obtained from
National Centre for Cell Science (NCCS), Pune (India) and
cultivated in Dulbecco’s modified Eagle’s red medium
(DMEM) (Sigma Life Science, USA) containing 10 % fetal
bovine serum (FBS). The cells (2000 cells per well) were seeded
in a 96-well micro plate containing 100 µL of Dulbecco’s
modified Eagle’s red medium + 10 % fetal bovine serum medium
per well and incubated at 37 °C with 5 % CO2. The cells were
treated with different concentration of compounds up to 72 h
for every 24 h interval. Controls were maintained with 0.5 %
DMSO. After 72 h treatment, 5 µL of 3-(4,5-dimethylthiazol-
2-yl)-2,5-diphenyltetrazoliumbromide (MTT) reagent (R&D
Systems, USA) along with 45 µL of phenol red free Dulbecco’s
modified Eagle’s red medium (Sigma Life Science, USA)
without fetal bovine serum was added to each well and plates
were incubated at 37 °C with 5 % CO2 for 4 h. Thereafter,
50 µL of solubilization buffer (R&D Systems, USA) was added
to each well to dissolve the coloured formazan crystals produced
by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-
tetrazoliumbromide.After 24 h, the optical density was measured
at 550 nm using microplate reader (Bio-Rad, USA).
Antioxidant activity (DPPH) method: The DPPH free
radical scavenging activity of the six novel analogs (3a-3f)
was measured according to the method developed by Chew
et al. [24]. The different concentrations of the titled compounds
i.e. 100, 200, 300, 400 and 500 µg/mL were prepared in DMSO.
1 mL of each concentration was mixed with 4 mL of the
0.004 % (w/v) solution of DPPH prepared in methanol. The
reaction mixture was kept for incubation in dark for 30 min.
Methanol was used as control and Ascorbic acid was used as
positive control. The absorbance was measured at 517 nm.
The DPPH scavenging activity (%) was calculated by using
the following formula:
1.31 (t, J = 3.0 Hz, 3H), 3.73 (s, 3H), 2.03 (d, J = 6.12 Hz,
2H), 5.67 (s, 1H), 6.68 (t, J = 6.32 Hz, 1H), 6.75 (d, J = 7.42
Hz, 1H), 7.01 (m, 3H), 7.10 (s, 1H), 7.23 (t, J = 8.0 Hz, 1H),
7.61 (d, J = 6.68 Hz, 1H), 8.18 (s, 1H): 13C NMR (100 MHz,
DMSO-d6): δ 15.05, 55.87, 64.03, 66.76, 111.73, 112.05,
114.75, 115.39, 117.44, 119.50, 127.65, 133.55, 133.97,
148.06, 148.35, 149.46, 164.05 ESI-MS: m/z 299 (M+H).
Calculated mass for the formula. C17H18N2O3 -298. Calculated
C, 68.44, H, 6.08, N, 9.39 %; Found: C, 68.47, H, 6.11, N,
9.37 %.
2,3-Dihydro-2-(2,3,4-trimethoxy-6-methylphenyl)-
quinazolin-4(1H)-one (3c): This compound was obtained as
1
a light yellow solid; m.p. 170-172 °C. H NMR (400 MHz,
DMSO-d6): δ 2.51 (s, 3H), 3.71 (s, 6H), 3.80 (s, 3H), 6.26 (s,
1H), 6.72 (m, 4H), 7.23 (t, J = 7.10 Hz, 1H), 7.63 (d, J = 7.10
Hz, 1H), 7.91 (s, 1H): 13C NMR (100 MHz, DMSO-d6): δ
20.74, 56.19, 60.64, 61.52, 61.89, 111.67, 114.48, 115.01,
117.09, 122.47, 127.78, 133.32, 134.78, 139.79, 149.47,
152.80, 153.25, 164.48; ESI-MS: m/z 329 (M+H). Calculated
mass for the formula C18H20N2O4 -328. Calculated C, 65.84,
H, 6.14, N, 8.53 %; Found: C, 65.85, H, 6.18, N, 8.56 %.
2,3-Dihydro-2-(1,3-diphenyl-1H-pyrazol-4-yl)quinazolin-
4(1H)-one (3d): This compound was obtained as a white solid;
m.p. 192-194 °C. 1H NMR (400 MHz, DMSO-d6): δ 5.90 (s,
1H), 6.67 (s, 2H), 7.07 (s, 1H), 7.5 (m, 8H), 7.67 (s, 1H), 7.80
(s, 2H), 7.96 (s, 2H), 8.3 (s, 1H), 8.9 (s, 1H): 13C NMR (100
MHz, DMSO-d6): δ 60.57, 115.01, 115.95, 118.14, 118.64,
120.76, 126.91, 127.96, 128.57, 128.69, 128.80, 129.86, 130.0,
132.77, 133.54, 139.69, 148.99, 151.22, 164.45; ESI-MS: m/
z 367 (M+H). Calculated mass for the formula C23H18N4O -
366. Calculated C, 75.39, H, 4.95, N, 15.29 %; Found: C,
75.42, H, 4.92, N, 15.26 %.
2,3-Dihydro-2-[3-(4-chlorophenyl)-1-phenyl-1H-
pyrazol-4-yl]quinazolin-4(1H)-one (3e): This compound was
1
obtained as a white solid; m.p. 198-200 °C. H NMR (400
MHz, DMSO-d6): δ 5.9 (s, 1H), 6.77 (d, J = 6.86 Hz, 2H),
7.04 (s, 1H), 7.29 (t, J = 6.75 Hz, 2H), 7.36 (t, J = 6.30 Hz,
1H), 7.50 (m, 2H), 7.67 (d, J = 6.82 Hz, 2H), 7.86 (d, J = 7.4
Hz, 2H), 7.96 (d, J = 7.09 Hz, 2H), 8.27 (s, 1H), 8.88 (s,1H):
13C NMR (100 MHz, DMSO-d6): δ 60.57, 115.06, 115.97,
118.18, 118.71, 120.81, 120.85, 127.04, 127.94, 128.80,
130.01, 130.40, 131.74, 133.32, 133.53, 139.59, 148.92,
148.99, 164.45; ESI-MS: m/z 401 (M+H). Calculated mass
for the formula C23H17 ClN4O -400. Calculated C, 68.91, H,
4.27, N, 13.98 %; Found: C, 68.94, H, 4.22, N, 14.01 %.
2,3-Dihydro-2-[3-(4-methoxyphenyl)-1-phenyl-1H-
pyrazol-4-yl]quinazolin-4(1H)-one (3f): This compound was
(A0 − As )
DPPH scavenging activity (%) =
×100
A0
where, A0 = absorbance of the control, As = absorbance of the
sample.
RESULTS AND DISCUSSION
With the aim of developing a new method for the synthesis
of 2-aryl-2,3-dihydroquinazolin-4(1H)-ones, we attempted to
study for the formation of titled compounds by condensing
2-aminobenzamide with 2-cyano, 3-methoxy benzaldehyde
in different catalysts such as SnCl2, NiSO4, celite, NaF, NaCl,
ceric sulphate and various solvents like methanol, ethanol,
1
obtained as a white solid; m.p. 180-182 °C. H NMR (400
MHz, DMSO-d6): δ 3.77 (s, 3H), 5.86 (s, 1H), 6.77 (m, 2H),