Synthesis and cytotoxicity of novel chrysin derivatives

Article abstract of DOI:10.1007/s00044-010-9395-1

A series of chrysin derivatives 8a-8v were prepared and tested in vitro against HCT-116 (human colon cancer cell line), Hela (human cervical carcinoma cell line), DU-145 (human prostate cell line), K562 (human leukemia cell line), and SGC-7901 (human gastric cancer cell line). The chemical structures of these compounds were confirmed by means of MS, IR, ¹H NMR, ¹³C NMR, and elemental analysis. Among these derivatives, 7-(2-(piperazin-1- yl)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, 8n, had the strongest activity against HCT-116, Hela, DU-145, K562, and SGC-7901 cells. Springer Science+Business Media, LLC 2010.

Full text of DOI:10.1007/s00044-010-9395-1

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2011) 20:838–846
DOI 10.1007/s00044-010-9395-1
ORIGINAL RESEARCH
Synthesis and cytotoxicity of novel chrysin derivatives
•
Kun Hu Wei Wang Hong Cheng
•
•
•
ShaSha Pan Jie Ren
Received: 22 January 2010 / Accepted: 22 July 2010 / Published online: 15 August 2010
Ó Springer Science+Business Media, LLC 2010
Abstract A series of chrysin derivatives 8a–8v were pre-
pared and tested in vitro against HCT-116 (human colon
cancer cell line), Hela (human cervical carcinoma cell line),
DU-145 (human prostate cell line), K562 (human leukemia
cell line), and SGC-7901 (human gastric cancer cell line).
The chemical structures of these compounds were confirmed
causes of death and morbidity. Cancer treatments may
involve surgery, radiotherapy, and chemotherapy and often a
combination of two or all three is employed. Natural com-
pounds from plants play a significant role in cancer chemo-
therapy but in spite of successes there is still much activity
directed to finding novel anticancer agents (Farnsworth
et al., 1985; Cragg et al., 1997; Da Rocha et al., 2001).
Chrysin (5,7-dihydroxyflavone, shown in Scheme 1), a
polyphenolic compound available in foods of plant origin,
belongs to the flavone subclass of flavonoids usually
occurring as glycosylated forms in plants. It has been
reported to have many different biological activities such as a
antibacterial (Qais et al., 1996), antioxidant (Hecker et al.,
1996), anti-inflammatory (Fishkin and Winslow, 1997), an-
tiallergic (Pearce et al., 1984), anti-virus (Cardenas et al.,
2006), and anxiolytic activities (Wolfman et al., 1994).
Chrysin can also display anticancer effect, and inhibit a
series of human cancer cell lines (Habtemariam, 1997).
However, few reports have been dedicated to the improve-
ment of the anticancer activities and the structure–activity
relationships of chrysin derivatives (Li et al., 2009; Babu
et al., 2006). Our research interest now is focused on the
modification of chrysin. In this article, chrysin was total
synthesized by Baker–Venkataraman rearrangement. To
increase the anticancer properties of chrysin, we prepared
chrysin derivatives in which chrysin ring system linked to the
different amines separated by 2 carbon spacers at C-7 posi-
tion (Li et al., 2009; Babu et al., 2006). These derivatives,
compared with their parent compound, displayed significant
anticancer activities against HCT-116 (human colon cancer
cell line), Hela (human cervical carcinoma cell line), DU-
145 (human prostate cell line), K562 (human leukemia cell
line), and SGC-7901 (human gastric cancer cell line), and all
the synthetic compounds were well characterized by their
spectral characteristics.
1
by means of MS, IR, H NMR, 13C NMR, and elemental
analysis. Among these derivatives, 7-(2-(piperazin-1-
yl)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, 8n, had
the strongest activity against HCT-116, Hela, DU-145,
K562, and SGC-7901 cells.
O
O
N
N
.
H
OH
O
8n
Keywords Synthesis ꢀ Chrysin ꢀ Cytotoxicity ꢀ
MTT assay
Introduction
A significant part of drug discovery in the past few years has
been focused on agents to prevent or treat cancer. This is not
surprising because, in most developed countries and, to an
increasing extent, cancer is among the three most common
K. Hu (&) ꢀ W. Wang ꢀ H. Cheng ꢀ S. Pan ꢀ J. Ren (&)
Faculty of Chemistry & Chemical Engineering,
Jiangsu Polytechnic University, Changzhou 213164,
People’s Republic of China
e-mail: hukun1979@163.com
J. Ren
e-mail: renjie2006@163.com
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Med Chem Res (2011) 20:838–846
839
O
O
Cl
MeO
OH
MeO
O
HO
OH
Me2SO4
KOH/Pyridine
3'
K2CO3/Acetone
K2CO3/Acetone
OMe O
OMe O
OH
O
1
2
3
2'
1
4'
5'
8
MeO
O
2
9
MeO
OH
HO
7
O
1'
CH3COOH/H2SO4
Py HCl
6'
10
6
3
4
5
OH
OMe O
OMe O
O
O
6
5
4
O
O
O
O
O
R
Br
1,2-dibromoethane
K2CO3
22 amines
8m R =
OH
O
OH
7
8
N
N
N
-NHCH3
-N(CH2CH3)2
N
8a R =
8b R =
8g R =
8h R =
8s R =
8t R =
8u R =
-NHCH2CH2OH
-N(CH2CH2OH)2
-N((CH2)2CH3)2
-NH(CH2)2CH3
8n R =
8o R =
N
N
N
N
NH
8c R = -NHCH(CH3)2
-N(CH(CH3)2)2
-N((CH2)3CH3)2
8i R =
8j R =
8k R =
8l R =
8d R =
8e R =
-NH(CH2)3CH3
-NHC(CH3)3
-N(CH3)2
N CH3
NPh
8p R =
8v R =
-NHPh
H
N
8q R =
8r R =
N
N
O
8f R =
Scheme 1 General synthesis of 8a–8v
Chemistry and biological activity
poured into water (100 ml). The precipitated solid was fil-
tered, washed with water, and crystallized from ethanol to
give 2 as white powders. Yield, 90%. FAB-MS, m/z:
197(M ? 1). IR mmax(cm-1, KBr): 1619 (C=O), 2944(OH).
1H NMR(CDCl3, 300 MHz): 2.61(3H, s,COCH3), 3.83(3H,
s,CH3O-6), 3.87(3H,s,CH3O-4), 5.92(1H, d, J = 2.6 Hz, H-
5), 6.06(1H, d, J = 2.7 Hz, H-3), 14.03(1H, s, OH). 13C
NMR(CDCl3, 300 MHz): 32.8(COCH3), 55.5(29 OCH3),
90.7(C-5), 93.5(C-3), 106.0(C-1), 162.9(C-6), 166.1(C-2),
167.6(C-4), 203.1(C=O). Anal. Calcd. for C10H12O4: C,
61.22, H, 6.16. Found: C, 61.35, H, 6.27.
1H NMR and 13C NMR spectra were recorded on a Bruker
AM 500(500-MHz) or AM 300(300-MHz) spectrometer
with Me4Si as internal standard. All the chemical shifts (d)
are expressed as parts per million, and coupling constants
(J) are given as hertz. Mass Spectra (MS) were recorded on
a Mariner System 5304 Mass spectrometer. IR spectra were
recorded on a Nicolet IR-460 spectrometer. Elemental
analysis was performed on a CHN-O-Rapid instrument and
was within 0.4% of the theoretical values. All the
reagents were commercial materials used without further
purification.
2-acetyl-3,5-dimethoxyphenyl benzoate(3)
2-hydroxy-4,6-dimethoxyacetophenone (2)
A mixture of 2 (392 mg, 2 mmol), K2CO3 (414 mg,
3 mmol), benzoyl chloride (552 mg, 2.4 mmol), and 15 ml
acetone was stirred at room temperature for 8 h, and then
the mixture was poured into ice-cooled water (100 ml).
The precipitated solid was filtered, washed with water, and
A mixture of 1 (0.01 mmol, 1.68 g), K2CO3 (3.03 g,
0.02 mol), Me2SO4 (2 ml, 0.02 mol), and 30 ml acetone was
stirred at room temperature for 4 h, and then the mixture was
123

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Med Chem Res (2011) 20:838–846
crystallized from ethanol to give 3 as white powders. Yield,
84%. FAB-MS, m/z : 301(M ? 1). IR mmax(cm-1, KBr):
1678(C=O), 3 118(OH). 1H NMR(CDCl3, 300 MHz):
2.47(3H, s, COCH3), 3.82(3H, s, CH3O-3), 3.86(3H, s,
CH3O-5), 6.37(1H, d, J = 2.3 Hz, H-6), 6.41(1H, d, J =
2.1 Hz, H-4), 7.47–7.63 (3H, m, H-40,50,60), 8.13(2H,
m, H-20,30). 13C NMR(CDCl3, 300 MHz): 31.9(COCH3),
55.6(OCH3), 55.9(OCH3), 96.7(C-4), 100.2(C-6), 117.4(C-2),
128.4(C-20,60), 129.3(C-40), 130.1(C-30,50), 133.6(C-10),
131.5(C-10), 159.9(C-9), 160.6(C-5), 160.9(C-2), 164.0(C-
7), 177.6(C-4). Anal. Calcd. for C17H14O4: C, 72.33, H,
5.00. Found: C, 72.21, H, 4.92.
5,7-dihydroxy-2-phenyl-4H-chromen-4-one (6)
A mixture of 5 (100 mg, 0.33 mmol) and Pyridine
Hydrochloride (1 g, 8.69 mmol) was warmed to 220°C for
15 min and then the mixture was cooled to room temper-
ature, acidified with 5% hydrochloric acid (20 ml) and
followed by extraction with EtOAc (29 30 ml). The
organic phase was dried (MgSO4) for 10 min, and the
mixture was filtered and evaporated. The residue was
purified by column chromatography (petroleum ether/
EtOAc) to give 6 as yellow powder. Yield, 68%. FAB-MS
149.8(C-1),
159.1(C-3),
162.2(COO),
165.0(C-5),
199.2(C=O). Anal. Calcd. for C17H16O5: C, 67.99, H, 5.37.
Found: C, 68.05, H, 5.42.
1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylpropane-
1,3-dione (4)
1
m/z: 255(M ? 1). IR mmax(cm-1, KBr): 1652 (C=O). H
A solution of 3 (100 mg, 0.26 mmol) in 5 ml of anhydrous
pyridine was prepared and warmed to 50°C. To the solution
was added hot pulverized potassium hydroxide(35 mg,
0.63 mmol), followed by heating at 50°C for 1 h, and then
the mixture was cooled to room temperature and acidified
with 5% hydrochloric acid (20 ml). The precipitated solid
was filtered, washed with water, and purified by column
chromatography (petroleum ether/EtOAc) to give 4 as
yellow powder. Yield, 71%. FAB-MS, m/z : 301(M ? 1).
NMR(DMSO-d6, 500 MHz) : 6.23(1H, d, J = 1.8 Hz, H-6),
6.53(1H, d, J = 1.7 Hz, H-8), 6.98(1H, s, H-3), 7.56–7.63(3H,
m, H-40,50,60), 8.08(2H, m, H-20,30), 10.92(1H, s, OH-5),
12.83(1H, s, OH-7). 13C NMR (DMSO-d, 500 MHz):
94.4(C-8), 99.3(C-6), 104.3(C-3), 105.5(C-10), 126.7(C-
20,60), 129.4(C-30,50), 131.0(C-40), 132.3(C-10), 157.8(C-9),
161.8(C-2), 163.5(6C-5), 164.7(C-7), 182.1(C-4). Anal.
Calcd. for C15H10O4: C, 70.86, H, 3.96. Found: C, 70.91,
H, 3.99.
1
IR mmax(cm-1, KBr): 1665(C=O), 3 165(OH). H NMR
(CDCl3, 300 MHz): 3.85(3H, s, CH3O-6), 3.88(3H, s, CH3
O-4), 3.92(2H, s, –COCH2CO–), 6.39(1H, d, J = 2.8 Hz,
H-2), 6.43(1H, d, J = 2.7 Hz, H-5), 7.42–7.61(3H, m, H-
40,50,60), 8.17(2H, m, H-20,30). 13C NMR(CDCl3, 300 MHz):
52.9(COCH2CO), 55.9(29 OCH3), 93.2(C-5), 95.6(C-3),
102.9(C-1), 128.8(C-20,60), 129.7(C-30,50), 132.3(C-40),
136.5(C-10), 161.7(C-6), 162.4(C-2), 167.8(C-4), 195.7(29
C=O). Anal. Calcd. for C17H16O5: C, 67.99, H, 5.37.
Found: C, 68.11, H, 5.49.
7-(2-bromoethoxy)-5-hydroxy-2-phenyl-4H-chromen-
4-one (7)
To a solution of 6 (500 mg, 1.96 mmol) in 45 ml of anhy-
drous acetone was added 1,2-dibromoethane (3 ml,
0.035 mol) and potassium carbonate(544 mg, 3.93 mmol),
followed by heating at reflux temperature for 24 h until the
starting material 6 disappeared. To the reaction mixture was
added ice water, dropwise. The mixture was distilled to form
yellow solid. Recrystallization of the solid from 30 ml ace-
tone gave the key intermediate 7 as yellow powder. Yield,
87.2%. FAB-MS m/z: 362(M ? 1). IR mmax(cm-1, KBr):
1660 (C=O). 1H NMR(CDCl3, 500 MHz): 3.84–3.86(2H, t,
J = 10.5 Hz, OCH2CH2), 4.46–4.48(2H, t, J = 10.5 Hz,
OCH2), 6.43(1H, s, H-6), 6.88(1H, s, H-8), 7.06(1H, s, H-3),
7.58–7.65(3H, m, H-40,50,60), 8.10–8.12(2H, m, H-20,30).
13C NMR(CDCl3, 500 MHz): 30.7(OCH2CH2), 68.4(CH2),
93.4(C-8), 98.5(C-6), 105.1(C-3), 105.3(C-10), 126.4(C-20,
60), 129.0(C-30,50), 130.5(C-40), 132.1(C-10), 157.2(C-9),
161.2(C-5), 163.5(C-2), 163.8(C-7), 182.0(C-4). Anal.
Calcd. for C17H13BrO4: C, 56.53, H, 3.63. Found: C, 56.67,
H, 3.75.
5,7-dimethoxy-2-phenyl-4H-chromen-4-one (5)
A solution of 4 (100 mg, 0.26 mmol) in 5 ml of glacial
acetic acid was prepared and warmed to 90°C. To the
solution was added 98% concentrated sulfuric acid
(0.05 ml), followed by heating at 90°C for 1 h and then
the mixture was cooled to room temperature and
poured into ice-cooled water (100 ml). The precipi-
tated solid was filtered, washed with water, and crystallized
from ethanol to give 5 as white solid. Yield, 72%. FAB-
MS, m/z : 283(M ? 1). IR mmax(cm-1, KBr): 1647(C=O).
1H NMR(CDCl3, 300 MHz): 3.91(3H, s, CH3O-7), 3.96
(3H, s, CH3O-5), 6.38(1H, d, J = 2.6 Hz, H-8), 6.58(1H, d,
J = 2.7 Hz, H-6), 6.68(1H, s, H-3), 7.49(3H, m, H-40,50,
60), 7.87(2H, m, H-20,30). 13C NMR(CDCl3, 300 MHz):
55.7(OCH3), 56.4(OCH3), 92.8(C-6), 96.2(C-8), 109.0(C-
10), 109.3(C-3), 125.9(C-20,60), 128.9(C-30,50), 131.1(C-40),
General procedures for preparation of 8a–8v
To a solution of 7 (100 mg, 0.277 mmol) in 15 ml of
CH3CN was added different amines (0.415 mmol) and
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Med Chem Res (2011) 20:838–846
841
potassium carbonate (57 mg, 0.415 mmol), followed by
heating at reflux temperature for 8–24 h until the starting
material disappeared. To the reaction mixture was added
ice water, dropwise. The precipitated solid was filtered,
washed with water. The residue was purified with a silica
gel column and was eluted with dichloromethane: metha-
nol = 40:1 to afford corresponding products.
93.1(C-8), 98.7(C-6), 105.8(C-3), 105.9(C-10), 126.3(C-20,
60), 129.1(C-30,50), 131.4(C-40), 131.8(C-10), 157.8(C-9),
162.2(C-5), 164.0(C-2), 164.9(C-7), 182.5(C-4). Anal.
Calcd. for C20H21NO4: C, 70.78, H, 6.24. Found: C, 70.89,
H, 6.31.
7-(2-(butylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8d)
7-(2-(methylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8a)
Yield, 71.5%. FAB-MS m/z: 354(M ? 1). IR mmax(cm-1
,
KBr): 1660 (C=O). 1H NMR(CDCl3, 500 MHz): 0.94–
0.95(3H, t, J = 7 Hz, NH(CH2)3CH3), 1.36–1.37(2H, m,
NH(CH2)2CH2CH3), 1.39–1.40(2H, m, NHCH2CH2CH2CH3),
2.69–2.72(2H, t, J = 14.5 Hz, NHCH2(CH2)2CH3), 3.04–
3.06(2H, t, J = 9.5 Hz, OCH2CH2), 4.13–4.16(2H, t,
J = 9.5 Hz, OCH2), 6.38(1H, s, H-6), 6.52(1H, s, H-8),
6.68(1H, s, H-3), 7.51–7.54(3H, m, H-40,50,60), 7.87–
7.89(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz):
13.9(N(CH2)3CH3), 20.4(N(CH2)2CH2CH3), 32.1(NCH2
CH2CH2CH3), 48.4(NCH2(CH2)2CH3), 49.5(OCH2CH2),
68.1(OCH2), 93.1(C-8), 98.7(C-6), 105.8(C-3), 105.9(C-10),
126.3(C-20,60), 129.1(C-30,50), 131.4(C-40), 131.8(C-10),
157.8(C-9), 162.2(C-5), 164.0(C-2), 164.9(C-7), 182.5(C-
4). Anal. Calcd. for C21H23NO4: C, 71.37, H, 6.56. Found:
C, 71.29, H, 6.48.
Yield, 74.1%. FAB-MS m/z: 312(M ? 1). IR mmax(cm-1
,
1
KBr): 1657 (C=O). H NMR(CDCl3, 500 MHz): 2.53(3H,
s, CH3), 3.00–3.02(2H, t, J = 10 Hz, OCH2CH2),4.14–4.16-
(2H, t, J = 10 Hz, OCH2), 6.38(1H, s, H-6), 6.52(1H, s,
H-8), 6.67(1H, s, H-3), 7.49–7.56(3H, m, H-40,50,60),
7.88–7.89(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz):
36.3(CH3), 50.4(OCH2CH2), 67.8(OCH2), 93.2(C-8),
98.6(C-6), 105.7(C-3), 105.8(C-10), 126.2(C-20, 60),
129.0(C-30,50), 131.2(C-40), 132.8(C-10), 157.7(C-9),
161.2(C-2), 163.9(C-5), 164.8(C-7), 182.4(C-4). Anal.
Calcd. for C18H17NO4: C, 69.44, H, 5.50. Found: C, 69.37, H,
5.45.
7-(2-(propylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8b)
7-(2-(tert-butylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8e)
Yield, 81.2%. FAB-MS m/z: 340(M ? 1). IR mmax(cm-1
,
KBr): 1660 (C=O). 1H NMR(CDCl3, 500 MHz): 0.94–0.97(3H,
t, J = 14.5 Hz, NHCH2CH2CH3), 1.54–1.59(2H, m, NHCH2
CH2CH3), 2.66–2.69(2H, t, J = 14.5 Hz, NHCH2CH2CH3),
3.04–3.06(2H, t, J = 10 Hz, OCH2CH2), 4.12–4.15(2H, t,
J = 10 Hz, OCH2), 6.38(1H, s, H-6), 6.52(1H, s, H-8),
6.67(1H, s, H-3), 7.49–7.55(3H, m, H-40,50,60), 7.88–
7.89(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz): 11.7(NCH2
CH2CH3), 23.1(N CH2CH2CH3), 48.4(OCH2CH2),
51.7(CH2CH2CH3), 68.1(OCH2), 93.1(C-8), 98.7(C-6),
105.8(C-3), 105.9(C-10), 126.3(C-20,60), 129.1(C-30,50),
131.4(C-40), 131.8(C-10), 157.8(C-9), 162.2(C-5), 164.0(C-
2), 164.9(C-7), 182.5(C-4). Anal. Calcd. for C20H21NO4: C,
70.78, H, 6.24. Found: C, 70.86, H, 6.34.
Yield, 57.3%. FAB-MS m/z: 354(M ? 1). IR mmax(cm-1
,
1
KBr): 1659 (C=O). H NMR(CDCl3, 500 MHz): 1.16(9H,
s, NHC(CH3)3), 2.98–3.00(2H, t, J = 9.8 Hz, OCH2CH2),
4.14–4.16(2H, t, J = 9.8 Hz, OCH2), 6.38(1H, s, H-6),
6.52(1H, s, H-8), 6.67(1H, s, H-3), 7.52–7.55(3H, m, H-
40,50,60), 7.87–7.89(2H, m, H-20,30). 13C NMR(CDCl3,
500 MHz): 29.0(NHC(CH3)3), 41.5(OCH2CH2), 50.3(NH
C(CH3)3), 69.2(OCH2), 93.1(C-8), 98.7(C-6), 105.8(C-3),
105.9(C-10), 126.3(C-20,60), 129.0(C-30,50), 131.4(C-40),
131.8(C-10), 157.8(C-9), 162.2(C-5), 164.9(C-2), 164.9(C-
7), 182.5(C-4). Anal. Calcd. for C21H23NO4: C, 71.37, H,
6.56. Found: C, 71.31, H, 6.46.
7-(2-(isopropylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8c)
7-(2-(dimethylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8f)
Yield, 62%. FAB-MS m/z: 340(M ? 1). IR mmax(cm-1
,
Yield, 82.2%. FAB-MS m/z: 326(M ? 1). IR mmax(cm-1
,
1
KBr): 1658 (C=O). H NMR(CDCl3, 500 MHz): 1.11(6H,
d, J = 6 Hz, NHCH(CH3)2), 2.89(1H, m, NHCH(CH3)2),
3.02–3.04(2H, t, J = 10.5 Hz, OCH2CH2), 4.14–4.16(2H,
t, J = 10.5 Hz, OCH2), 6.38(1H, s, H-6), 6.52(1H, s, H-8),
6.67(1H, s, H-3), 7.51–7.55(3H, m, H-40,50,60), 7.87–
7.89(2H, m, H-20, 30). 13C NMR(CDCl3, 500 MHz):
22.9(CH(CH3)2), 46.0(OCH2CH2), 48.6(CH), 68.5(OCH2),
KBr): 1659 (C=O). 1H NMR(CDCl3, 500 MHz): 2.35(6H, s,
NH(CH3)2), 2.78–2.79(2H, t, J = 7.5 Hz, OCH2CH2),
4.01–4.03(2H, t, J = 7.5 Hz, OCH2), 6.39(1H, s, H-6),
6.53(1H, s, H-8), 6.67(1H, s, H-3), 7.52–7.56(3H, m, H-
40,50,60), 7.88–7.89(2H, m, H-20,30). 13C NMR(CDCl3,
500 MHz):46.0(2CH3), 58.0(OCH2CH2), 66.9(OCH2),
93.4(C-8), 98.7(C-6), 106.0(C-3), 106.2(C-10), 126.4(C-20,
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60), 129.1(C-30,50), 131.2(C-40), 131.8(C-10), 157.8(C-9),
162.3(C-5), 164.1(C-2), 164.9(C-7), 182.5(C-4). Anal.
Calcd. for C19H19NO4: C, 70.14, H, 5.89. Found: C, 70.25,
H, 5.97.
Calcd. for C23H27NO4: C, 72.42, H, 7.13. Found: C, 72.25,
H, 6.98.
7-(2-(dibutylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8j)
7-(2-(diethylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8g)
Yield, 71.6%. FAB-MS m/z: 410(M ? 1). IR mmax(cm-1
,
KBr): 1659 (C=O). 1H NMR(CDCl3, 500 MHz): 0.91–
0.94(6H, t, J = 14.5 Hz, N((CH2)3CH3)2), 1.32–1.36(4H,
m, N((CH2)2CH2CH3)2), 1.43–1.46(4H, m, N(CH2CH2
CH2CH3)2), 2.50–2.53(4H, t, J = 14.8 Hz, N(CH2(CH2)2
CH3)2), 2.87–2.90(2H, t, J = 12.1 Hz, OCH2CH2), 4.08–
4.10(2H, t, J = 12.1 Hz, OCH2), 6.37(1H, s, H-6),
6.52(1H, s, H-8), 6.66(1H, s, H-3), 7.52–7.55(3H, m,
H-40,50,60), 7.88–7.89(2H, m, H-20,30). 13C NMR(CDCl3,
500 MHz): 14.0(N((CH2)3CH3)2), 20.6(N((CH2)2CH2
CH3)2), 29.5(N(CH2CH2CH2CH3)2), 52.6(OCH2CH2),
54.8(N(CH2(CH2)2CH3)2), 67.5(OCH2), 93.1(C-8), 98.7(C-
6), 105.7(C-3), 105.9(C-10), 126.3(C-20,60), 129.1(C-30,50),
131.4(C-40), 131.8(C-10), 157.8(C-9), 162.1(C-5), 163.9(C-
2), 165.0(C-7), 182.4(C-4). Anal. Calcd. for C25H31NO4:
C, 73.32, H, 7.63. Found: C, 73.49, H, 7.75.
Yield, 76.7%. FAB-MS m/z: 354(M ? 1). IR mmax(cm-1
,
KBr): 1661 (C=O). 1H NMR(CDCl3, 500 MHz): 1.07–
1.09(6H, t, J = 14 Hz, N(CH2CH3)2), 2.62–2.67(4H, q,
J = 21.5 Hz, N(CH2CH3)2), 2.88–2.91(2H, t, J = 12 Hz,
OCH2CH2), 4.11–4.13(2H, t, J = 12 Hz, OCH2), 6.38(1H,
s, H-6), 6.51(1H, s, H-8), 6.67(1H, s, H-3), 7.52–7.56(3H,
m, H-40,50,60), 7.88–7.89(2H, m, H-20,30). 13C NMR(CDCl3,
500 MHz):
12.0(N(CH2CH3)2),
47.9(N(CH2CH3)2),
51.5(OCH2CH2), 67.5(OCH2), 93.2(C-8), 98.7(C-6),
105.7(C-3), 105.9(C-10), 126.3(C-20,60), 129.1(C-30,50),
131.4(C-40), 131.8(C-10), 157.8(C-9), 162.2(C-5), 164.0(C-
2), 165.0(C-7), 182.5(C-4). Anal. Calcd. for C21H23NO4:
C, 71.37, H, 6.56. Found: C, 71.52, H, 5.71.
7-(2-(dipropylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8h)
7-(2-(cyclohexylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8k)
Yield, 73.9%. FAB-MS m/z: 382(M ? 1). IR mmax(cm-1
,
1
KBr): 1658 (C=O). H NMR(CDCl3, 500 MHz): 0.90(6H,
t, J = 13.5 Hz, N(CH2CH2CH3)2), 1.49–1.50(4H, m, N(CH2
CH2CH3)2), 2.39–2.41(4H, t, J = 13.5 Hz, N(CH2CH2
CH3)2), 6.37(1H, s, H-6), 6.50(1H, s, H-8), 6.66(1H, s, H-
3), 7.51–7.55(3H, m, H-40,50,60), 7.88–7.90(2H, m, H-
20,30). 13C NMR(CDCl3, 500 MHz): 11.8(N(CH2CH2
CH3)2), 20.5(N(CH2CH2CH3)2), 52.7(OCH2CH2), 57.1(N
(CH2CH2CH3)2), 67.5(OCH2), 93.2(C-8), 98.7(C-6),
105.7(C-3), 105.9(C-10), 126.3(C-20,60), 129.1(C-30,50),
131.4(C-40), 131.8(C-10), 157.8(C-9), 162.2(C-5), 163.9(C-
2), 165.0(C-7), 182.5(C-4). Anal. Calcd. for C23H27NO4:
C, 72.42, H, 7.13. Found: C, 72.36, H, 7.03.
Yield, 83.1%. FAB-MS, m/z: 380(M ? 1). IR mmax(cm-1
,
KBr): 1652 (C=O). 1H NMR(CDCl3, 500 MHz): 1.07–1.30
(6H, m, (CH2)3), 1.63–1.77(6H, m, (CH2)2), 2.48–2.52(1H,
m, CH), 3.05–3.07(2H, t, J = 10.3 Hz, OCH2CH2),
4.13–4.16(2H, t, J = 10.4 Hz, OCH2), 6.38(1H, s, H-6),
6.53(1H, s, H-8), 6.68(1H, s, H-3), 7.50–7.57(3H, m, H-
40,50,60), 7.88–7.89(2H, m, H-20,30). 13C NMR(CDCl3,
500 MHz): 25.0((CH2CH2)2CH2), 26.1((CH2CH2)2CH2),
33.6((CH2CH2)2CH2), 45.5(OCH2CH2), 56.6(CH), 68.6
(OCH2), 93.1(C-8), 98.7(C-6), 105.8(C-3), 105.9(C-10),
126.3(C-20,60), 129.1(C-30,50), 131.3(C-40), 131.8(C-10),
157.8(C-3), 162.1(C-5), 164.0(C-2), 164.9(C-7), 182.5(C-
4). Anal. Calcd. for C23H25NO4: C, 72.80, H, 6.64. Found: C,
72.69, H, 6.55.
7-(2-(diisopropylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8i)
7-(2-morpholinoethoxy)-5-hydroxy-2-phenyl-4H-chromen-
4-one (8l)
Yield, 54.8%. FAB-MS m/z: 382(M ? 1). IR mmax(cm-1
,
1
KBr): 1644 (C=O). H NMR(CDCl3, 500 MHz): 1.06(2H,
d, J = 6.5 Hz, 4CH3), 2.84–2.87(2H, t, J = 14.2 Hz,
OCH2CH2), 3.03–3.08(2H, m, N(CH)2), 3.95–3.97(2H, t,
J = 14.2 Hz, OCH2), 6.36(1H, s, H-6), 6.50(1H, s, H-8),
6.68(1H, s, H-3), 7.51–7.53(3H, m, H-40,50,60), 7.88–
7.89(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz):
20.4(4CH3), 44.1(OCH2CH2), 49.6(2CH), 69.9(OCH2),
93.1(C-8), 98.7(C-6), 105.8(C-3), 105.9(C-10), 126.3(C-
20,60), 129.0(C-30,50), 131.4(C-40), 131.7(C-10), 157.8(C-9),
162.2(C-5), 163.9(C-2), 165.1(C-7), 182.4(C-4). Anal.
Yield, 84%. FAB-MS, m/z: 368(M ? 1). IR mmax(cm-1
,
1
KBr): 1663 (C=O). H NMR(CDCl3, 500 MHz): 2.59(4H,
s, N(CH2)2), 2.84–2.87(2H, t, J = 11.5 Hz, OCH2CH2),
3.74(4H, s, O(CH2)2), 4.19–4.22(2H, t, J = 11.5 Hz,
OCH2), 6.38(1H, s, H-6), 6.52(1H, s, H-8), 6.67(1H, s, H-3),
7.53–7.60(3H, m, H-40,50,60), 7.88–7.90(2H, m, H-20,30).
13C NMR(CDCl3, 500 MHz): 54.1(N(CH2)2), 57.3(OCH2
CH2), 66.6(OCH2), 66.9(O(CH2)2), 93.3(C-8), 98.6(C-6),
105.8(C-3), 105.9(C-10), 126.3(C-20,60), 129.1(C-30,50),
123

Med Chem Res (2011) 20:838–846
843
131.4(C-40), 131.8(C-10), 157.8(C-9), 162.3(C-5), 164.0(C-
2), 164.7(C-7), 182.5(C-4). Anal. Calcd. for C21H21NO5: C,
68.65, H, 5.76. Found: C, 68.71, H, 5.88.
Calcd. for C22H24N2O4: C, 69.46, H, 6.36. Found: C, 69.23,
H, 6.28.
7-(2-(4-benzylpiperazin-1-yl)ethoxy)-5-hydroxy-2-phenyl-
4H-chromen-4-one (8p)
7-(2-(piperidin-1-yl)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8m)
Yield, 58.4%. FAB-MS, m/z: 457(M ? 1). IR mmax(cm-1
,
Yield, 88.3%. FAB-MS, m/z: 366(M ? 1). IR mmax(cm-1
,
KBr): 1658 (C=O). 1H NMR(CDCl3, 500 MHz): 2.52(8H, s,
N(CH2CH2)2), 2.84–2.86(2H, t, J = 11.5 Hz, OCH2CH2),
3.52(2H, s, CH2), 4.16–4.18(2H, t, J = 11.5 Hz, OCH2),
6.36(1H, s, H-6), 6.50(1H, s, H-8), 6.68(1H, s, H-3),
7.31–7.32(5H, m, CH2C6H5), 7.50–7.56(3H, m, H-40,50,60),
7.87–7.88(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz):
52.9(N(CH2CH2)2), 53.6(N(CH2CH2)2), 56.7(OCH2CH2),
63.0(CH2), 66.5(OCH2), 93.2(C-8), 98.6(C-6), 105.7(C-3),
105.9(C-10), 126.2(C-20,60), 127.0(C-400), 128.2(C-300,500),
129.0(C-200,600), 129.2(C-20,60), 131.2(C-40), 131.8(C-10),
137.9(C-100), 157.7(C-9), 162.1(C-5), 163.9(C-2), 164.7(C-7),
182.4(C-4). Anal. Calcd. for C28H28N2O4: C, 73.66, H, 6.18.
Found: C, 73.58, H, 6.11.
KBr): 1661 (C=O). 1H NMR(CDCl3, 500 MHz): 1.60–
1.64(6H, m, N(CH2)2(CH2)3), 2.52(4H, s, N(CH2)2),
2.79–2.82(2H, t, J = 12 Hz, OCH2CH2), 4.17–4.19(2H, t,
J = 12 Hz, OCH2), 6.38(1H, s, H-6), 6.57(1H, s, H-8),
6.67(1H, s, H-3), 7.51–7.55(3H, m, H-40,50,60),
7.88–7.89(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz):
24.1(N(CH2CH2)2CH2), 25.9(N(CH2CH2)2), 55.1(N(CH2
CH2)2), 57.5(OCH2CH2), 66.8(OCH2), 93.2(C-8), 98.7(C-
6), 105.7(C-3), 105.9(C-10), 126.3(C-20,60), 129.1(C-30,50),
131.4(C-40), 131.8(C-10), 157.8(C-9), 162.2(C-5), 164.0(C-
2), 164.9(C-7), 182.5(C-4). Anal. Calcd. for C22H23NO4:
C, 72.31, H, 6.34. Found: C, 72.37, H, 6.42.
7-(2-(piperazin-1-yl)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8n)
7-(2-(pyrrolidin-1-yl)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8q)
Yield, 73.2%. FAB-MS, m/z: 367(M ? 1). IR mmax(cm-1
,
Yield, 81.6%. FAB-MS, m/z: 352(M ? 1). IR mmax(cm-1
,
KBr): 1660 (C=O). 1H NMR(CDCl3, 500 MHz): 2.56–
2.66(4H, m, N(CH2CH2)2), 2.82–2.88(4H, m, N(CH2
CH2)2), 2.92–2.93(2H, t, J = 9.5 Hz, OCH2CH2), 4.18–
4.20(2H, t, J = 11.2 Hz, OCH2), 6.38(1H, s, H-6), 6.52(1H,
s, H-8), 6.67(1H, s, H-3), 7.51–7.55(3H, m, H-40,50,60),
7.88–7.89(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz):
46.0(N(CH2CH2)2), 55.0(N(CH2CH2)2), 57.4(OCH2CH2),
66.5(OCH2), 93.2(C-8), 98.7(C-6), 105.8(C-3), 105.9(C-10),
126.3(C-20,60), 129.1(C-30,50), 131.3(C-40), 131.8(C-10),
157.7(C-9), 162.2(C-5), 164.0(C-2), 164.9(C-7), 182.5(C-4).
Anal. Calcd. for C21H22N2O4: C, 68.84, H, 6.05. Found: C,
68.96, H, 6.13.
KBr): 1660 (C=O). 1H NMR(CDCl3, 500 MHz):1.81–
1.83(4H, m, N(CH2CH2)2), 2.64(4H, s, N(CH2CH2)2),
2.92–2.95(2H, t, J = 11.5 Hz, OCH2CH2), 4.17–4.20(2H, t,
J = 11.5 Hz, OCH2), 6.39(1H, s, H-6), 6.53(1H, s, H-8),
6.67(1H, s, H-3), 7.51–7.55(3H, m, H-40,50,60), 7.87–
7.89(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz): 23.5(N
(CH2CH2)2), 54.7(N(CH2CH2)2, OCH2CH2), 67.9(OCH2),
93.2(C-8), 98.7(C-6), 105.8(C-3), 105.9(C-10), 126.3(C-
20,60), 129.1(C-30,50), 131.4(C-40), 131.8(C-10), 157.8(C-9),
162.2(C-5), 164.0(C-2), 164.9(C-7), 182.5(C-4). Anal.
Calcd. for C21H21NO4: C, 71.78, H, 6.02. Found: C, 71.57,
H, 5.94.
7-(2-(4-methylpiperazin-1-yl)ethoxy)-5-hydroxy-2-phenyl-
4H-chromen-4-one (8o)
7-(2-(1H-imidazol-1-yl)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8r)
Yield, 68.2%. FAB-MS, m/z: 381(M ? 1). IR mmax(cm-1
,
Yield, 73.8%. FAB-MS, m/z: 349(M ? 1). IR mmax(cm-1
,
1
KBr): 1638 (C=O). H NMR(CDCl3, 500 MHz): 2.30(3H,
s, NCH3), 2.42–2.48(8H, m, 2N(CH2)2), 2.84–2.86(2H, t,
J = 11.3 Hz, OCH2CH2), 4.17–4.19(2H, t, J = 11.3 Hz,
OCH2), 6.38(1H, s, H-6), 6.52(1H, s, H-8), 6.67(1H, s, H-
3), 7.51–7.54(3H, m, H-40,50,60), 7.88–7.89(2H, m, H-20,
30). 13C NMR(CDCl3, 500 MHz): 46.0(CH3), 53.6(N(CH2
CH2)2), 55.0(N(CH2CH2)2), 56.8(OCH2CH2), 66.7(OCH2),
93.3(C-8), 98.7(C-6), 105.8(C-3), 105.9(C-10), 126.3(C-20,
60), 129.1(C-30,50), 131.3(C-40), 131.8(C-10), 157.7(C-9),
162.1(C-5), 163.9(C-2), 164.9(C-7), 182.4(C-4). Anal.
KBr): 1657 (C=O). 1H NMR(CDCl3, 500 MHz): 4.28–
4.30(2H, t, J = 10 Hz, OCH2CH2), 4.38–4.4.(2H, t,
J = 10 Hz, OCH2), 6.34(1H, s, H-6), 6.48(1H, s, H-8),
6.66(1H, s, H-3), 7.05(1H, s, HC=CH), 7.09(1H, s,
HC=CH), 7.51–7.56(3H, m, H-40,50,60), 7.60(1H, s, N=CH),
7.86–7.88(2H, m, H-20,30). 13C NMR(CDCl3, 500 MHz):
46.1(OCH2CH2), 67.6(OCH2), 93.4(C-8), 98.2(C-6),
106.0(C-3), 106.1(C-10), 119.2(HC=CH), 126.3(C-20,60),
129.1(C-30,50), 131.1(C-40), 131.9(C-10), 137.5(N=C),
157.7(C-9), 162.1(C-5), 163.6(C-2), 164.1(C-7), 182.4(C-4).
123

844
Med Chem Res (2011) 20:838–846
7-(2-(benzylamino)ethoxy)-5-hydroxy-2-phenyl-4H-
chromen-4-one (8v)
Anal. Calcd. for C20H16N2O4: C, 68.96, H, 4.63. Found: C,
69.15, H, 4.81.
Yield, 62.1%. FAB-MS, m/z: 388(M ? 1). IR mmax(cm-1
,
7-(2-(2-methyl-1H-imidazol-1-yl)ethoxy)-5-hydroxy-2-
phenyl-4H-chromen-4-one (8s)
KBr): 1658 (C=O). 1H NMR(CDCl3, 500 MHz): 3.06–
3.08(2H, t, J = 11.5 Hz, OCH2CH2), 3.89(2H, s, NCH2),
4.15–4,17(2H, t, J = 11.5 Hz, OCH2), 6.37(1H, s, H-6),
6.52(1H, s, H-8), 6.69(1H, s, H-3), 7.33–7.36(5H, m,
CH2C6H5), 7.49–7.55(3H, m, H-40,50,60), 7.88–7.89(2H, m,
H-20,30). 13C NMR(CDCl3, 500 MHz): 47.8(OCH2CH2),
53.8(CH2), 68.3(OCH2), 93.1(C-8), 98.5(C-6), 105.8(C-3),
105.9(C-10), 126.3(C-20,60), 127.1(C-400), 128.1(C-200,600),
128.5(C-300,500), 129.1(C-30,50), 131.1(C-40), 131.8(C-10),
140.0(C-100), 157.8(C-9), 162.2(C-5), 164.0(C-2), 164.8(C-
7), 181.4(C-4). Anal. Calcd. for C24H21NO4: C, 74.40, H,
5.46. Found: C, 74, 33, H, 5.39.
Yield, 78.1%. FAB-MS, m/z: 363(M ? 1). IR mmax(cm-1
,
1
KBr): 1658 (C=O). H NMR(CDCl3, 500 MHz): 2.49(3H,
s, CH3), 4.27–4.29(2H, t, J = 8.5 Hz, OCH2CH2),
4.34–4.37(2H, t, J = 8.5 Hz, OCH2), 6.31(1H, s, H-6),
6.51(1H, s, H-8), 6.67(1H, s, H-3), 6.96(2H, s, HC=CH),
7.51–7.57(3H, m, H-40,50,60), 7.87–7.88(2H, m, H-20,30).
13C NMR(CDCl3, 500 MHz): 13.1(CH3), 45.1(OCH2
CH2), 67.5(OCH2), 93.2(C-8), 98.2(C-6), 105.9(C-3),
106.1(C-10), 119.3(HC=CH), 126.3(C-20,60), 127.7(HC=
CH), 129.1(C-30,50), 131.1(C-40), 131.9(C-10), 144.9(N=C),
157.7(C-9), 162.1(C-5), 163.7(C-2), 164.1(C-7), 182.4(C-
4). Anal. Calcd. for C21H18N2O4: C, 69.60, H, 5.01. Found:
C, 69.78, H, 5.19.
Biological activity
HCT-116, Hela, DU-145, K562, and SGC-7901 cell lines
were cultured and passaged in RPMI-1640 medium, sup-
plemented with 10% (v/v) inactive calf bovine serum, in a
humidified incubator at 37°C under an atmosphere of 5%
CO2. Stock solutions of tested compounds were prepared in
DMSO and were used for serial dilutions in culture med-
ium. The cytotoxicity assay was performed by a modifi-
cation of the MTT method (Mosmann, 1983).
7-(2-(20-hydroxyethylamino)ethoxy)-5-hydroxy-2-phenyl-
4H-chromen-4-one (8t)
Yield, 82.6%. FAB-MS, m/z: 342(M ? 1). IR mmax(cm-1
,
KBr): 1664 (C=O). 1H NMR(CDCl3, 500 MHz): 2.63–
2.65(2H, t, J = 11 Hz, NCH2CH2), 2.90–2.92(2H, t, J =
10.6 Hz, OCH2CH2), 3.46–3.48(2H, t, J = 11 Hz, NCH2
CH2), 4.14–4.16(2H, t, J = 10.6 Hz, OCH2), 6.41(1H, s,
H-6), 6.84(1H, s, H-8), 7.06(1H, s, H-3), 7.59–7.65(3H, m,
H-40,50,60), 8.10–8.12(2H, m, H-20,30). 13C NMR(CDCl3,
500 MHz): 47.7(OCH2CH2), 51.5(NCH2CH2), 60.4(NCH2
CH2), 68.5(OCH2), 93.1(C-8), 98.4(C-6), 104.8(C-3),
105.2(C-10), 126.3(C-20,60), 129.0(C-30,50), 130.5(C-40),
132.0(C-10), 157.2(C-9), 161.1(C-5), 163.3(C-2), 164.6(C-
7), 181.9(C-4). Anal. Calcd. for C19H19NO5: C, 66.85, H,
5.61. Found: C, 66.73, H, 5.54.
Results and discussion
Chrysin was total synthesized by Baker–Venkataraman
rearrangement in five steps (Scheme 1). Compound 4 was
the key intermediate for synthesis of chrysin, and it was
prepared by the action of benzoyl chloride on a pyridine
solution of Compound 3. The cyclization was effected by
use of glacial acetic acid containing hydrogen chloride or
sulfuric acid.
7-(2-(20,200-dihydroxydiethylamino)ethoxy)-5-hydroxy-2-
phenyl-4H-chromen-4-one (8u)
The synthesis of compounds 8a–8v was accomplished
according to the general pathway illustrated in Scheme 1.
Compound 7 was the key intermediate for synthesis of the
compounds investigated. It was usually prepared from
alkylation of 7-OH group by using 1,2-dibromoethane in
the presence of bases such as NaOH or K2CO3 (Reinholz
et al., 1990). To increase the anticancer properties of
chrysin derivatives, chrysin derivatives in which the
chrysin ring system is linked to the different amines were
investigated.
Yield, 73.6%. FAB-MS, m/z: 386(M ? 1). IR mmax(cm-1
,
KBr): 1660 (C=O). 1H NMR(CDCl3, 500 MHz): 2.64–
2.66(4H, t, J = 12 Hz, N(CH2CH2)2), 2.93–2.95(2H, t,
J = 10.8 Hz, OCH2CH2), 3.44–3.46(4H, t, J = 11.3 Hz,
N(CH2CH2)2), 4.38–4.40(2H, t, J = 10.3 Hz, OCH2),
6.39(1H, s, H-6), 6.83(1H, s, H-8), 7.05(1H, s, H-3),
7.55–7.63(3H, m, H-40,50,60), 8.10–8.12(2H, m, H-20,30).
13C NMR(CDCl3, 500 MHz): 53.2(OCH2CH2), 57.0(N
(CH2CH2)2), 59.4(N(CH2CH2)2), 67.3(OCH2), 93.1(C-8),
98.4(C-6), 104.8(C-3), 105.2(C-10), 126.3(C-20,60), 129.0(C-
30,50), 130.5(C-40), 132.0(C-10), 157.2(C-9), 161.1(C-5),
163.3(C-2), 164.5(C-7), 181.9(C-4). Anal. Calcd. for
C21H23NO6: C, 65.44, H, 6.02. Found: C, 65.56, H, 6.18.
All of the synthetic compounds gave satisfactory ana-
lytical and spectroscopic data, which were in full accor-
dance with their depicted structures.
Assays were performed in 96-well plates essentially as
described by Mosmann (1983). Pharmacological results are
123

Med Chem Res (2011) 20:838–846
845
against HCT-116, K562, and SGC-7901 was enhanced with
a shorter alkyl chain on N. In addition, the different alkylated
substituents on N had little effect against Hela and DU-145
cells.
Table 1 Human cancer cell line growth inhibition values (lM) for
the synthesized compounds
Compoud
IC50/(lM)
HCT-116
Hela
DU-145
K562
SGC-7901
In summary, a series of novel C(7) modified chrysin
derivatives were prepared. Our results supported published
data about flavones as interesting cytotoxic secondary
metabolites. Certainly, the presence of hydroxy in position
5 appears to play a non-negligible part in the antitumor
potency of tested compounds. However, the highest
potency is obtained when a piperazin-1-yl-ethoxy group is
present in position 7. These results contribute to further
understanding the critical molecular requirements that lead
to antitumor properties in the flavones series. Further in
vivo studies are warranted to confirm the biological activity
of the newly synthesized flavones and to investigate the
molecular mechanisms responsible for the antitumor
activity of the most active compounds with a potential
pharmaceutical use.
8a
2.5
3.72
56.6
[100
40.9
4.92
17.7
18.82
1.56
24.2
13.3
6.97
[100
1.7
2.95
1.4
7.8
4.8
8b
8c
1.5
12.9
[100
14.9
[100
17.9
12.9
[100
27.8
43.4
1.76
[100
16.9
4.9
11.1
[100
1.88
3.15
10.99
13.9
23.6
7.98
53.3
6.18
42.99
3.1
8.1
[100
1.85
2.75
17.7
3.17
8.4
8d
8e
2.7
1.87
6.2
8f
8g
8h
8i
9.8
38
4.6
18.1
44.2
4.98
[100
3.17
1.08
32.5
28.7
[100
7.3
8j
9.7
8k
8l
2.95
[100
[100
0.19
32.3
18.7
[100
4.2
8m
8n
8o
8p
8q
8r
0.46
[100
47.4
[100
10.8
9.7
0.78
[100
55.7
[100
5.55
7.83
5.05
59.2
69.8
[100
2.19
[100
23.9
[100
27.2
10.8
8.31
104.7
31.2
[100
45.4
Acknowledgments This research was supported by Jiangsu
Provincial Natural Science Foundation (No. BK2009549).
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3.2
8.2
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86.5
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