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d, J = 9.0 Hz, benzimidazole-C6H3), 7.74 (1H, d, J = 15.2 Hz, benzimidazole-
CH@CH), 7.77 (1H, d, J = 16.1 Hz, CH@CHAr), 7.91 (1H, d, J = 15.0 Hz,
benzimidazole-CH@CH)ppm; 13C NMR (100 MHz, DMSO-d6)
29.9, 55.5,
CH@CHAr), 7.21–7.26 (2H, m, CH3OC6H3), 7.40 (1H, s, benzimidazole-C6H2),
7.45 (1H, s, benzimidazole-C6H2), 7.65 (1H, d, J = 15.2 Hz, benzimidazole-
CH@CH), 7.68 (1H, d, J = 15.8 Hz, CH@CHAr), 7.78 (1H, d, J = 15.6 Hz,
benzimidazole-CH@CH), 9.21 (1H, s, OH)ppm; 13C NMR (100 MHz, DMSO-d6)
d 20.0, 20.2, 29.8, 55.7, 110.6, 112.0, 114.6, 119.2, 122.3, 123.2, 127.4, 127.5,
130.4, 131.6, 132.6, 135.1, 141.5, 143.8, 146.7, 147.7, 150.4, 187.6 ppm; 15e:
1H NMR (400 MHz, DMSO-d6) d 3.89 (3H, s, OCH3), 3.91 (3H, s, OCH3), 3.95 (3H,
s, NCH3), 6.79 (1H, d, J = 2.4 Hz, CH3OC6H3), 6.86 (1H, d, J = 16.1 Hz, CH@CHAr),
6.89 (1H, d, J = 8.3 Hz, CH3OC6H3), 6.98 (1H, dd, J = 8.9 and 2.3 Hz, CH3OC6H3),
7.14 (1H, dd, J = 8.3 and 2.0 Hz, benzimidazole-C6H3), 7.23 (1H, d, J = 2.0 Hz,
benzimidazole-C6H3), 7.70 (1H, d, J = 8.8 Hz, benzimidazole-C6H3), 7.74 (1H, d,
J = 16.3 Hz, benzimidazole-CH@CH), 7.77 (1H, d, J = 15.6 Hz, CH@CHAr), 7.91
(1H, d, J = 15.7 Hz, benzimidazole-CH@CH)ppm; 13C NMR (100 MHz, DMSO-d6)
d 29.9, 55.5, 55.6, 93.3, 111.9, 113.3, 114.5, 120.0, 122.1, 123.2, 127.2, 127.3,
130.0, 137.2, 137.3, 143.8, 146.7, 147.7, 150.4, 157.0, 187.6 ppm; 15f: 1H NMR
(400 MHz, DMSO-d6) d 3.91 (3H, d, J = 6.4 Hz, NCH3), 3.93 (3H, s, OCH3), 6.84
(1H, d, J = 16.3 Hz, CH@CHAr), 6.89 (1H, d, J = 8.4 Hz, CH3OC6H3), 7.14 (1H, d,
J = 8.3 Hz, CH3OC6H3), 7.24 (1H, d, J = 1.8 Hz, CH3OC6H3), 7.30 (1H, dd, J = 8.5
and 1.8 Hz, benzimidazole-C6H3), 7.35 (1H, dd, J = 22.7 and 1.8 Hz,
benzimidazole-C6H3), 7.71 (1H, d, J = 15.0 Hz, benzimidazole-CH@CH), 7.74
(1H, d, J = 11.6 Hz, benzimidazole-C6H3), 7.77 (1H, d, J = 16.3 Hz, CH@CHAr),
8.00 (1H, dd, J = 15.1 and 2.8 Hz, benzimidazole-CH@CH)ppm; 13C NMR
(100 MHz, DMSO-d6) d 30.1, 55.7, 78.2, 111.9, 112.3, 114.6, 122.3, 123.1,
126.8, 127.3, 127.5, 132.2, 135.3, 137.1, 143.4, 144.3, 146.7, 150.2, 150.3,
187.6 ppm; 15g: 1H NMR (400 MHz, DMSO-d6) d 3.84 (3H, s, OCH3), 4.06 (3H, s,
NCH3), 7.02 (1H, d, J = 8.2 Hz, CH3OC6H3), 7.24 (1H, d, J = 16.0 Hz, CH@CHAr),
7.27 (1H, s, CH3OC6H3), 7.29 (1H, dd, J = 8.3 and 1.7 Hz, CH3OC6H3), 7.74 (1H, d,
J = 15.0 Hz, benzimidazole-CH@CH), 7.81 (1H, d, J = 16.0 Hz, CH@CHAr), 7.82
(1H, d, J = 9.0 Hz, benzimidazole-C6H3), 7.89 (1H, d, J = 15.0 Hz, benzimidazole-
CH@CH), 8.23 (1H, dd, J = 9.0 and 2.1 Hz, benzimidazole-C6H3), 8.57 (1H, d,
J = 1.9 Hz, benzimidazole-C6H3), 9.25 (1H, s, OH)ppm; 13C NMR (100 MHz,
DMSO-d6) d 30.3, 56.2, 106.7, 109.8, 109.8, 115.2, 116.6, 119.6, 124.0, 124.6,
124.9, 126.9, 132.2, 134.7, 140.3, 142.7, 145.5, 146.9, 148.9, 187.8 ppm; 15h:
1H NMR (400 MHz, DMSO-d6) d 3.83 (3H, s, OCH3), 3.87 (3H, s, NCH3), 6.79 (1H,
d, J = 8.0 Hz, benzimidazole-C6H3), 6.86 (1H, s, benzimidazole-C6H3), 7.00 (1H,
d, J = 8.0 Hz, benzimidazole-C6H3), 7.21 (1H, d, J = 12.0 Hz, CH@CHAr), 7.26 (2H,
s, CH3OC6H3), 7.48 (1H, d, J = 12.0 Hz, CH3OC6H3), 7.60 (1H, d, J = 12.0 Hz,
benzimidazole-CH@CH), 7.67 (1H, d, J = 12.0 Hz, CH@CHAr), 7.77 (1H, d,
J = 12.0 Hz, benzimidazole-CH@CH) 9.23 (1H, s, OH), 9.57 (1H, s, OH)ppm;
13C NMR (100 MHz, DMSO-d6) d 30.2, 56.1, 95.5, 112.4, 114.0, 115.0, 120.5,
122.6, 123.7, 127.9, 128.0, 130.1, 137.2, 138.0, 144.1, 147.1, 147.7, 150.8, 155.4,
188.1 ppm.
d
55.7, 93.3, 111.9, 113.3, 115.7, 120.0, 123.0, 123.7, 126.2, 127.0, 127.1, 129.8,
137.3, 137.4, 144.1, 148.0, 149.8, 157.0, 187.6 ppm; 14f: 1H NMR (400 MHz,
DMSO-d6) d 3.91 (3H, d, J = 6.3 Hz, NCH3), 3.96 (3H, s, OCH3), 6.85 (1H, dd,
J = 16.3 and 2.50 Hz, CH@CHAr), 6.97 (1H, d, J = 8.0 Hz, CH3OC6H3), 7.12 (1H, s,
CH3OC6H3), 7.17 (1H, dd, J = 8.0 and 2.0 Hz, CH3OC6H3), 7.29 (1H, dd, J = 8.8 and
1.8 Hz, benzimidazole-C6H3), 7.35 (1H, dd, J = 39.3 and 1.5 Hz, benzimidazole-
C6H3), 7.71 (1H, t, J = 4.3 Hz, benzimidazole-CH@CH), 7.77 (1H, d, J = 16.0 Hz,
benzimidazole-C6H3), 7.78 (1H, dd, J = 16.0 and 2.00 Hz, CH@CHAr), 7.97 (1H,
dd, J = 15.0 and 2.0 Hz, benzimidazole-CH@CH)ppm; 13C NMR (100 MHz,
DMSO-d6) d 30.2, 56.0, 109.7, 109.9, 110.6, 115.0, 119.7, 120.9, 124.0, 124.3,
124.5, 124.7, 125.6, 127.0, 130.6, 130.9, 145.2, 147.0, 148.8, 187.9 ppm; 14g:
1H NMR (400 MHz, DMSO-d6) d 3.97 (3H, s, OCH3), 3.99 (3H, s, NCH3), 6.88 (1H,
d, J = 16.0 Hz, CH@CHAr), 6.98 (1H, d, J = 8.2 Hz, CH3OC6H3), 7.14 (1H, d,
J = 1.6 Hz, CH3OC6H3), 7.20 (1H, dd, J = 8.3 and 1.7 Hz, CH3OC6H3), 7.47 (1H, d,
J = 9.0 Hz, benzimidazole-C6H3), 7.74 (1H, d, J = 15.0 Hz, benzimidazole-
CH@CH), 7.81 (1H, d, J = 16.0 Hz, CH@CHAr), 8.05 (1H, d, J = 15.0 Hz,
benzimidazole-CH@CH), 8.28 (1H, dd, J = 8.9 and 2.1 Hz, benzimidazole-
C6H3), 8.74 (1H, d, J = 1.9 Hz, benzimidazole-C6H3) ppm; 13C NMR (100 MHz,
DMSO-d6) d 30.5, 56.0, 106.7, 109.7, 109.8, 115.0, 116.7, 119.4, 124.1, 124.4,
124.9, 126.9, 132.4, 134.4, 140.1, 142.2, 145.7, 146.9, 148.9, 187.6.ppm; 14h:
1H NMR (400 MHz, DMSO-d6) d 3.85 (3H, s, OCH3), 3.92 (3H, s, NCH3), 6.87 (1H,
d, J = 8.0 Hz, CH3OC6H3), 6.90 (1H, d, J = 9.2 Hz, benzimidazole-C6H2), 6.97 (1H,
s, benzimidazole-C6H3), 7.24 (1H, d, J = 16.0 Hz, CH@CHAr), 7.28 (1H, dd, J = 8.2
and 1.80 Hz, CH3OC6H3), 7.45 (1H, d, J = 2.0 Hz, CH3OC6H3), 7.53 (1H, d,
J = 8.8 Hz, benzimidazole-C6H3), 7.45 (1H, s, benzimidazole-C6H3), 7.74 (1H, d,
J = 14.8 Hz, benzimidazole-CH@CH), 7.75 (1H, d, J = 14.8 Hz, CH@CHAr), 7.81
(1H, d, J = 16.0 Hz, benzimidazole-CH@CH) 9.80 (2H, s, OH)ppm; 13C NMR
(100 MHz, DMSO-d6) d 30.2, 56.2, 95.6, 112.4, 114.0, 116.2, 120.5, 123.5, 124.1,
126.7, 127.6, 130.0, 137.2, 138.0, 144.5, 148.1, 148.4, 150.2, 155.4, 188.0 ppm.;
15a: 1H NMR (400 MHz, DMSO-d6) d 3.84 (3H, s, OCH3), 3.99 (3H, s, NCH3), 7.01
(1H, d, J = 8.8 Hz, CH3OC6H3), 7.22 (1H, d, J = 16.0 Hz, CH@CHAr), 7.27–7.34
(2H, m, CH3OC6H3), 7.27–7.34 (2H, m, benzimidazole-C6H4), 7.64 (1H, d,
J = 7.6 Hz, benzimidazole-C6H4), 7.70 (1H, d, J = 7.2 Hz, benzimidazole-C6H4),
7.71 (1H, d, J = 16.0 Hz, benzimidazole-CH@CH), 7.72 (1H, d, J = 15.6 Hz,
CH@CHAr), 7.83 (1H, d, J = 15.2 Hz, benzimidazole-CH@CH), 9.24 (1H, s,
OH)ppm; 13C NMR (100 MHz, DMSO-d6) d 29.7, 55.7, 110.8, 112.0, 114.6,
119.3, 122.2, 122.8, 123.1, 123.3, 127.2, 127.5, 131.4, 136.4, 142.7, 144.1, 146.7,
148.7, 150.5, 187.7 ppm; 15b: 1H NMR (400 MHz, DMSO-d6) d 2.51 (3H, s, CH3),
3.92 (3H, s, OCH3), 3.95 (3H, s, NCH3), 5.31 (1H, s, OH), 6.86 (1H, d, J = 16.1 Hz,
CH@CHAr), 6.89 (1H, d, J = 8.3 Hz, CH3OC6H3), 7.14 (1H, dd, J = 8.4 and 1.9 Hz,
CH3OC6H3), 7.18 (1H, d, J = 8.0 Hz, benzimidazole-C6H3), 7.24 (1H, d, J = 1.9 Hz,
CH3OC6H3), 7.28 (1H, d, J = 8.4 Hz, benzimidazole-C6H3), 7.61 (1H, s,
benzimidazole-C6H3), 7.76 (1H, d, J = 15.1 Hz, benzimidazole-CH@CH), 7.78
(1H, d, J = 16.2 Hz, CH@CHAr), 7.98 (1H, d, J = 15.1 Hz, benzimidazole-
CH@CH)ppm; 13C NMR (100 MHz, DMSO-d6) d 21.2, 29.9, 55.6, 110.3, 111.9,
114.5, 118.9, 122.2, 123.1, 125.0, 127.3, 127.5, 131.0, 132.0, 134.7, 143.1, 144.0,
146.7, 148.5, 150.4, 187.7 ppm; 15c: 1H NMR (400 MHz, DMSO-d6) d 2.73 (3H,
s, CH3), 3.92 (3H, s, OCH3), 3.94 (3H, s, NCH3), 6.88 (1H, d, J = 15.9 Hz,
CH@CHAr), 6.89 (1H, d, J = 8.2 Hz, CH3OC6H3), 7.12–7.28 (2H, m, CH3C6H3),
7.12–7.28 (3H, m, benzimidazole-C6H3), 7.77 (1H, d, J = 15.4 Hz,
benzimidazole-CH@CH), 7.77 (1H, d, J = 15.4 Hz, CH@CHAr), 7.96 (1H, d,
21. All experiments were carried out 24 h after cells were seeded. Chemical
compounds were dissolved in DMSO and diluted with DMEM medium to final
concentrations of 1, 5, 10, 20, and 40 lM. The tumor cells were incubated with
chemical compounds for 24 or 48 h before the MTT assay. A 3-(4,5-dimethyl-
thiazol-yl-2)-2,5-diphenyl tetrazolium bromide (MTT) reduction was
determined to examine the effect of chemical compounds on cell viability.
Briefly, following the treatment of cells with different concentrations of
chemical compound (final concentration, 1, 5, 10, 20, and 40
48 h, cells were incubated with MTT solution (0.5 mg/ml) for 3 h at 37 °C. The
violet precipitate (formazan) in MTT-treated cells was dissolved with 100 L of
lM) for 24 or
l
DMSO and then analyzed at a wavelength of 595 nm with a microplate reader
(Beckman Coulter, Brea, CA). Each assay was performed in triplicate. IC50 was
calculated by nonlinear regression analysis from a sigmoid dose–response
curve using the GraphPad Prism software ver 3.0 (Graph-Pad Software, CA,
U.S.A.) when R2 >0.95.
J = 15.0 Hz, benzimidazole-CH@CH)ppm; 13C NMR (100 MHz, DMSO-d6)
d
16.9, 30.5, 56.2, 108.7, 112.4, 115.2, 122.6, 123.3, 123.6, 123.9, 127.8, 128.0,
129.5, 131.9, 136.6, 142.7, 144.3, 147.2, 148.3, 150.9, 188.1 ppm; 15d: 1H NMR
(400 MHz, DMSO-d6) d 2.33 (3H, s, CH3), 2.37 (3H, s, CH3), 3.84 (3H, s, OCH3),
3.93 (3H, s, NCH3), 7.01 (1H, d, J = 8.8 Hz, CH3OC6H3), 7.20 (1H, d, J = 16.0 Hz,
22. MCF-7: Breast adenocarcinoma; SH-SY5Y: Human neuroblastoma; Hep-G2:
Human hepatocellular carcinoma; H460: Lung carcinoma.