1074
G.-Z. Jin et al.
7b: Yield 68%, m.p. 209-211oC; IR (cm−1): 3050, 1660, 7j: Yield 79%, m.p. 210-211oC; IR (cm−1): 3050, 1660,
1580, 1455, 1287, 1250; 1H-NMR (DMSO-d6, 300 MHz): 1620, 1580, 1455, 1287, 1280; 1H-NMR (DMSO-d6, 300
δ
3.15 (6H, s), 3.19 (6H, s), 5.11 (2H, s), 6.49 (1H, s), MHz): δ 3.13 (6H, s), 3.22 (6H, s), 5.26 (2H, s), 6.28
6.55-7.72 (4H, m), 7.73-7.78 (2H, m), 7.95-8.00(2H, m). (1H, s), 6.40-8.23 (11H, m). MS: m/z 451.57+H).
MS: m/z 435.84 (M+H).
Antiproliferative activity against p388 mouse
leukemic tumor cells
P388 mouse leukemia tumor cells were provided by
3.03 (6H, s), 3.08 (6H, s), 3.84 (3H, s), 5.18 the Shanghai Institute of Material Medical. P388
(2H, s), 5.97 (1H, s), 6.92-7.17 (4H, m), 7.65-7.70 (2H, cancer cells were seeded in 96 well flat-bottomed plates
7c: Yield 71%, m.p. 205-206oC; IR (cm−1): 3050, 1660,
1580, 1455, 1287, 1280, 1225; 1H-NMR (DMSO-d6, 300
MHz):
δ
m), 8.00-8.05 (2H, m). MS: m/z 431.48 (M+H).
and incubated in a medium containing 0.25% trypsin
digestion and 10% FBS and a penicillin-streptomycin
7d: Yield 75%, m.p. 215-216oC; IR (cm−1): 3050, 1660, mixture at 37.8oC in a humidified atmosphere of 5%
1580, 1455, 1287, 1285, 1225; 1H-NMR (DMSO-d6, 300 CO2 for 24 h. The test drugs were dissolved in di-
MHz):
(2H, s), 5.87 (1H, s), 6.90 (2H, d,
d, = 8.5 Hz), 7.65-7.70 (2H, m), 8.00-8.05 (2H, m). concentration of 1-500
MS: m/z 431.48 (M+H).
δ
3.03 (6H, s), 3.08 (6H, s), 3.85 (3H, s), 5.10 methyl sulfoxide (DMSO). The incubation medium
= 8.5Hz), 7.15 (2H, was replaced with each test medium to produce a final
M and no drug in 2 ml DMSO
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µ
over 2 days. The cells were incubated for 48 h. Cell
survival rates were determined using the MTT assay.
7e: Yield 80%, m.p. 253-255oC; IR (cm−1): 3050, 1660,
1580, 1455, 1287, 1250; 1H-NMR (DMSO-d6, 300 MHz):
RESULTS AND DISCUSSION
δ
2.33 (3H, s), 3.05 (6H, s), 3.09 (6H, s), 5.05 (2H, s),
5.97 (1H, s), 7.19-7.21 (2H, d, = 8.31 Hz), 7.48-7.51
(2H, = 8.31 Hz), 7.63-7.69 (2H, m), 8.06-8.12 (2H,
m). MS: m/z 415.61 (M+H).
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Chemistry
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1,4-Diamino-9,10-anthraquinone was used as the
starting material. In total fifteen novel compounds
were designed and synthesized. Their chemical struc-
7f: Yield 67%, m.p. 271-273oC; IR (cm−1): 3050-3520, tures were elucidated based on their IR, 1H-NMR and
3050, 1660, 1580, 1455, 1287, 1230; 1H-NMR (DMSO- MS spectra. In the synthesis design, in which reduc-
d6, 300 MHz):
5.99 (1H, s), 6.88-6.90 (2H,
(2H, = 8.30 Hz), 7.65-7.70 (2H, m), 8.00-8.05 (2H, ing to the polarity, bulkiness and hydrophilicity of
m). MS: m/z 416.41 (M+H).
δ
3.11 (6H, s), 3.17 (6H, s), 5.02 (2H, s), tion, methylation, chlorination and condensation were
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= 8.30 Hz), 7.12-7.16 carried out using classical chemical reactions accord-
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each substituting side chain group. In each case, the
reaction can be easily carried out and controlled. The
7g: Yield 90%, m.p. 235-236oC; IR (cm−1): 3050, 1660, synthetic technique used has been well-established
1580, 1455, 1287, 1250; 1H-NMR (DMSO-d6, 300 MHz): and the yield was also high. In many cases, the product
δ
3.13 (6H, s), 3.19 (6H, s), 4.83 (2H, s), 5.98 (1H, s), obtained required no further purification and could be
6.89-6.92 (2H, = 8.35 Hz), 7.52-7.55 (2H, = 8.35 used directly for the next reaction step, such as the
Hz), 7.71-7.76 (2H, m), 8.01-8.06 (2H, m). MS: m/z chlorination of 2-hydroxymethyl-1,4-bis(dimethyl)amino-
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436.10 (M+H).
9,10-anthraquinone.
During the synthesis, the first crucial steps were
7h: Yield 86%, m.p. 258-259oC; IR (cm−1): 3350, 3050, protection of the carbonyl and amino group from the
1
1660, 1580, 1455, 1287, 1250; H-NMR (CDCl3, 300 starting material 1,4-diamino-9,10-anthraquinone. If
MHz):
(2H, s), 6.11 (1H, s), 6.88-6.90 (2H,
7.14 (2H, = 8.35 Hz), 7.59-7.65 (2H, m), 7.96- two, the following reducing step could reduce the car-
8.01(2H, m). MS: m/z 431.46+H).
δ
3.05 (6H, s), 3.11 (6H, s), 5.05 (2H, s), 5.12 foramide was introduced at the 2-position of the an-
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= 8.35 Hz), 7.12- thraquinone ring without protecting either of these
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bonyl group as well as the foramide group. The aromatic
primary amine is very active and can easily be oxidized.
7i: Yield 81%, m.p. 224-246oC; IR (cm−1): 3050, 1660, Together with many other unwanted reactions such
1580, 1455, 1287, 1280, 1220; 1H-NMR (DMSO-d6, 300 as substitution and condensation reaction, the reac-
MHz):
(2H, s), 5.32 (2H, s), 5.97 (1H, s), 6.87 (1H, d,
Hz), 7.11-7.15 (2H, m), 7.65-7.70 (2H, m), 8.00-8.05 duced to a hydroxyl group using NaBH4, and the re-
(2H, m). MS: m/z 461.39. sulting hydroxyl groups along with the amino group
δ
3.04 (6H, s), 3.35 (6H, s), 3.84 (3H, s), 5.21 tion could produce many side products.
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= 8.40
The carbonyl group of anthraquinone was first re-