Med Chem Res (2013) 22:5066–5075
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4-(3,4-Dichlorobenzylidene)-1-(4-oxo-2-phenyl-4H-
Ar–CH=C), 8.45 (s, 1H, H-5), 7.8 (d, 1H, H-8)
J = 5.48 Hz, 8.19 (d, 1H, H-7) J = 7.4 Hz, 8.08 (dd, 4H,
H-200, 300, 500, 600) J = 7.32 Hz, J = 7.8 Hz, 7.69 (d, 2H,
H-60, 6*) J = 8.64 Hz, 7.5–7.6 (m, 6H, 30, 40, 50, 3*, 4*,
5*), 7.16 (d, 2H, H-20, 2*) J = 8.6 Hz, 9.78 (s, 1H, H–Ar–
OH); 13C NMR DMSO-d6, 100 MHz, d 163.87 (C-2),
104.85 (C-3), 183.31 (C-4), 120.20 (C-5), 127.45 (C-6),
128.27 (C-7), 117.94 (C-8), 152.88 (C-9), 124.14 (C-10),
130.33 (C-10), 126.35 (C-20, C-60), 128.71 (C-30, C-50),
128.00 (C-40), 165.92 (C-2**), 130.83 (C-4**), 170.38 (C-
5**), 109.18 (C-6**), 127.80 (C-100), 125.68 (C-200, C-600),
114.89 (C-500, C-300), 158.37 (C-400), 128.41 (C-1*), 126.94
(C-2*, C-6*), 128.88 (C-5*, C-3*), 130.62 (C-4*).
chromen-6-yl)-2-phenyl-1H-imidazol-5-one (7c)
Yield: 58 %; m.p.: 268 °C; Rf value: 0.367; UV kmax (nm):
292; IR (KBr) cm-1: 1685 (C=O str. imidazolidinone),
1649 (C=O str. flavone), 1600 (C=N str. imidazolidinone);
ESI–MS m/z 555.4 (M ? H2O); 1H NMR DMSO-d6,
400 MHz, d 7.02 (s, 1H, H-3), 7.16 (s, 1H, Ar–CH=C),
8.46 (s, 1H, H-5), 7.8 (d, 1H, H-8) J = 9.04 Hz, 8.18 (d,
1H, H-7) J = 8.84 Hz, 8.01 (d, 2H, H-20, 2*) J = 7.4 Hz,
8.1 (d, 2H, H-60, 6*) J = 6.84 Hz, 7.89 (s, 1H, H-200) 7.67
(d, 1H, H-600) J = 8.4 Hz, 7.58 (m, 7H, 30, 40, 50, 500, 3*,
4*, 5*); 13C NMR DMSO-d6, 100 MHz, d 163.86 (C-2),
105.39 (C-3), 183.02 (C-4), 120.18 (C-5), 129.14 (C-6),
131.37 (C-7), 117.86 (C-8), 152.62 (C-9), 124.16 (C-10),
130.34 (C-10), 126.48 (C-20, C-60), 128.69 (C-30, C-50),
128.01 (C-40), 164.87 (C-2**), 130.57 (C-4**), 171.73
(C-5**), 108.89 (C-6**), 134.81 (C-100), 125.66 (C-200),
127.76 (C-600), 133.69 (C-500), 130.57 (C-300), 132.67
(C-400), 128.01 (C-1*), 126.28 (C-2*, C-6*), 128.85 (C-5*,
C-3*), 130.61 (C-4*).
Biological activity
The synthesized analogues 7a–e were evaluated for their
in vitro cytotoxic potential by the MTT assay (Denizot and
Lang, 1986) and SRB assay (Skehan et al., 1990). The
most active compound from the above cytotoxicity screen
was studied further by Hoechst staining analysis and flow
cytometric analysis (Duvall and Wyllie, 1986; Hu et al.,
2009) to establish the apoptotic potential. After confirming
the apoptotic potential of compound 7d, it was further
studied to evaluate the in vivo anticancer activity. Ehrlich
tumour is a rapidly growing carcinoma with very aggres-
sive behaviour and is able to grow in almost all mice strains
(Chen and Watkins, 1970). The in vivo study was per-
formed using Ehrlich’s ascites tumour model on Albino
mice, and the activity was compared to that of Cisplatin.
The study was carried out as per the procedure reported by
earlier workers (Devi et al., 1998). The results obtained for
in vivo anticancer studies were analysed statistically and
the level of significance determined by one-way ANOVA
followed by Dunnet multiple comparisons test in the case
of mean survival time and by Tukey test in the case of
percentage increase in body weight. An in vivo anti-
inflammatory screen by the method of Winter et al. (1962)
also was performed. Statistical analysis was carried out
using one-way ANOVA followed by Post hoc Scheffe’s
test, and p \ 0.05 was considered significant in the case of
anti-inflammatory evaluation. The animal care and han-
dling was carried out in accordance with the guidelines
issued by the Institutional Animal Ethics Committee,
Kasturba Medical College, Manipal University, Manipal,
and the study was approved by the committee (Clearance
certificate no.—IAEC/KMC/02/2006–2007).
4-(3,4-Dimethoxybenzylidene)-1-(4-oxo-2-phenyl-4H-
chromen-6-yl)-2-phenyl-1H-imidazol-5-one (7d)
Yield: 48 %; m.p.: 240 °C; Rf value: 0.306. UV kmax (nm):
296; IR (KBr) cm-1: 1681 (C=O str. imidazolidinone),
1631 (C=O str. flavone), 1604 (C=N str. imidazolidinone);
ESI–MS m/z 547.1 (M ? H2O); 1H NMR DMSO-d6,
400 MHz, d 3.62 (d, 6H, H–OCH3) J = 12.6 Hz, 6.98 (s,
1H, H-3), 7.01 (s, 1H, Ar–CH=C), 8.448 (s, 1H, H-5), 7.8
(d, 1H, H-8) J = 9.08 Hz, 8.2 (d, 1H, H-7) J = 7.4 Hz, 8.1
(d, 4H, H-20, 2*, 60, 6*) J = 5.92 Hz, 7.23 (d, 1H, H-200)
J = 8.2 Hz, 7.3 (d, 2H, H-500, 600) J = 13.48 Hz, 7.51–7.6
(m, 6H, 30, 40, 50, 3*, 4*, 5*); 13C NMR DMSO-d6,
100 MHz, d 164.62 (C-2), 104.92 (C-3), 182.26 (C-4),
120.89 (C-5), 127.48 (C-6), 128.72 (C-7), 118.18 (C-8),
152.89 (C-9), 124.63 (C-10), 130.43 (C-10), 125.98 (C-20,
C-60), 128.97 (C-30, C-50), 127.89 (C-40), 163.79 (C-2**),
130.38 (C-4**), 170.36 (C-5**), 108.93 (C-6**), 128.18
(C-100), 120.61 (C-200), 110.67 (C-600), 149.94 (C-500),
119.73 (C-300), 151.71 (C-400), 128.58 (C-1*), 126.21
(C-2*, C-6*), 128.93 (C-5*, C-3*), 130.14 (C-4*), 55.89
(C–OCH3 at C-400 and C-500).
4-(4-Hydroxybenzylidene)-1-(4-oxo-2-phenyl-4H-
chromen-6-yl)-2-phenyl-1H-imidazol-5-one (7e)
Yield: 51 %; m.p.: 262 °C; Rf value: 0.347; UV kmax (nm):
296; IR (KBr) cm-1: 3244 (br. Ar–OH str), 1674 (C=O str.
imidazolidinone), 1626 (C=O str. flavone), 1601 (C=N str.
imidazolidinone); ESI–MS m/z 503.1 (M ? H2O); 1H
NMR DMSO-d6, 400 MHz, d 7.01 (s, 1H, H-3), 7.2 (s, 1H,
Conclusion
Five novel imidazolidinone analogues of flavone have been
synthesized in good yields in an attempt to explore the
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