Cytotoxic apigenin derivatives from Chrysopogon aciculatis

Article abstract of DOI:10.1021/np2007796

Four new apigenin derivatives, 7-de-O-methylaciculatin (1), 8-C-β-d-boivinopyranosylapigenin (2), aciculatinone (3), and 4′-O-glucosylaciculatin (4), along with eight known compounds, apigenin-8-carbaldehyde (5), kaempferol, tricin, taxifolin, 6,7,4′- trihydroxyflavone, trans-oxyresveratrol, aciculatin, and luteolin-7-sulfate, were isolated from an ethanolic extract of Chrysopogon aciculatis. Their chemical structures were elucidated by spectroscopic methods. Among the known compounds, the natural occurrence of apigenin-8-carbaldehyde and luteolin-7-sulfate is demonstrated for the first time. Some of the isolates were evaluated for cytotoxic activity against human cancer cell lines including MCF-7, H460, HT-29, and CEM.

Full text of DOI:10.1021/np2007796

Article
pubs.acs.org/jnp
Cytotoxic Apigenin Derivatives from Chrysopogon aciculatis
†
†
‡
§,⊥
⊥
Chien-Chang Shen, Jing-Jy Cheng, Horng-Liang Lay, Szu-Yuan Wu, Ching-Li Ni,
∥
,⊥
Che-Ming Teng, and Chien-Chih Chen*
†
National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China
‡
Department of Plant Industry, National Pingtung University of Science and Technolog, Pingtung, Taiwan, Republic of China
Department of Radiation Oncology, Chia-Yi Christian Hospital, Chia Yi City, Taiwan, Republic of China
§
⊥
Department of Biotechnology, Hungkuang University, Taichung, Taiwan, Republic of China
∥
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
*
S Supporting Information
ABSTRACT: Four new apigenin derivatives, 7-de-O-methylaci-
culatin (1), 8-C-β-D-boivinopyranosylapigenin (2), aciculatinone
(
3), and 4′-O-glucosylaciculatin (4), along with eight known
compounds, apigenin-8-carbaldehyde (5), kaempferol, tricin,
taxifolin, 6,7,4′-trihydroxyflavone, trans-oxyresveratrol, aciculatin,
and luteolin-7-sulfate, were isolated from an ethanolic extract of
Chrysopogon aciculatis. Their chemical structures were elucidated
by spectroscopic methods. Among the known compounds, the
natural occurrence of apigenin-8-carbaldehyde and luteolin-7-
sulfate is demonstrated for the first time. Some of the isolates
were evaluated for cytotoxic activity against human cancer cell
lines including MCF-7, H460, HT-29, and CEM.
RESULTS AND DISCUSSION
The ethanolic extract of the whole grass C. aciculatis was
he whole grass of Chrysopogon aciculatis (Poaceae) has
■
T
been used as pasturage in Taiwan. A DNA binding agent1,
aciculatin, was isolated from this plant in the previous study.
Recently, as part of our program on the discovery of potential
successively partitioned between H O and EtOAc and then n-
2
BuOH. The EtOAc-soluble material was sequentially chromato-
graphed on silica gel, Sephadex LH-20, and C -OPN columns
2
−6
cytotoxic principles from natural sources,
the EtOH extract
18
of C. aciculatis was partitioned with H O and EtOAc, and the
2
to give three new flavones, 7-de-O-methylaciculatin (1), 8-C-β-
D-boivinopyranosylapigenin (2), and aciculatinone (3), and six
latter extract was found to show potent cytotoxicity against
human tumor cells. Further investigation of C. aciculatis led to
the isolation and characterization of four new apigenin
derivatives (1−4) and eight known compounds. The structures
of the known compounds were elucidated on the basis of
7
8
9
known compounds, kaempferol, tricin, taxifolin, 6,7,4′-
10
11
1
trihydroxyflavone, trans-oxyresveratrol, and aciculatin.
The n-BuOH-soluble material was repeatedly separated on
silica gel, Sephadex LH-20, and C -OPN columns to afford the
1
18
spectroscopic methods or identified by comparison of their H
new flavone 4′-O-glucosylaciculatin (4) and two known
flavones, apigenin-8-carbaldehyde (5) and luteolin-7-sulfate.
and 13C NMR data with literature data. Some of the isolates
were evaluated for their cytotoxic activities against human
cancer cell lines including MCF-7, H460, HT-29, and CEM.
12
13
Luteolin-7-sulfate was previously synthesized by sulfation of
13
luteolin and was isolated from a natural source for the first
time.
Compound 1 was obtained as a light yellow powder, and its
molecular formula was deduced as C H O from its HREIMS
21
20
8
and NMR data. The IR spectrum of 1 showed the presence of
−
1
−1
1
hydroxy (3500 cm ) and carbonyl (1659 cm ) groups. Its H
and 13C NMR spectra were similar to those of aciculatin, an
apigenin C-glycoside, except for the absence of one methoxy
1
1
group (Table 1). The analysis of the aromatic regions in the H
and C NMR spectra suggested compound 1 was a
monosubstituted apigenin. The presence of a β-C-digitoxosyl
1
3
Received: September 27, 2011
Published: January 24, 2012
©
2012 American Chemical Society and
American Society of Pharmacognosy
198
dx.doi.org/10.1021/np2007796 | J. Nat. Prod. 2012, 75, 198−201

Journal of Natural Products
Article
Table 1. H and 13C NMR Data of Compounds from Chrysopogon aciculatis
1
a
b
b
b
c
c
1
2
3
4
5
δH (J in
Hz)
position
δH (J in Hz)
6.67 s
δC
δH (J in Hz)
δC
δH (J in Hz)
δC
δH (J in Hz)
δC
δC
2
3
4
5
6
7
8
9
164.7
164.7
165.5
162.5
164.1
103.7 6.66 s
183.2
103.8 6.69 s
183.2
103.9 6.95 s
183.5
103.5 7.01 s
182.4
103.5
181.5
166.7
98.8
162.0
162.0
163.6
161.0
6.17 s
100.4 6.17 s
163.3
100.5 6.48 s
163.7
95.9
6.53 s
95.3
6.26 s
163.3
106.7
156.1
105.8
123.4
162.1
107.7
154.9
104.6
124.3
168.5
104.1
157.9
103.6
120.7
129.0
105.4
106.4
154.3
153.8
1
1
2
0
105.3
105.0
′
123.0
123.2
′, 6′
8.07 d (9.0)
7.01 d (9.0)
129.5 8.02 d (9.0)
129.4 8.08 d (8.4)
129.6 8.16 d (8.4)
128.5 8.10 d
8.4)
(
3′, 5′
116.9 7.00 d (9.0)
116.9 7.06 d (8.4)
116.9 7.19 d (8.4)
116.5 6.94 d
8.4)
116.0
161.6
(
4
5
7
1
′
162.1
162.1
162.1
160.5
-OH
-OCH3
″
12.95 s
12.94 s
13.41 s
3.97 s
13.24 s
14.01 br s
10.38 s
57.0
72.2
3.89 s
56.6
64.9
5.77 dd (2.4, 11.4)
2.11 ddd (2.4, 11.4,
70.3
38.9
5.77 dd (2.4, 12.0)
70.3
33.9
5.40 dd (3.0,
2.0)
5.44 dd (2.0,
12.0)
188.3
1
2″
1.84 td (2.4, 14.4)
2.51 dd (3.0,
13.8)
45.6
1.63 dd (2.4,
14.4)
36.6
1
4.4)
.20 ddd (2.4, 3.6,
4.4)
2
2.33 ddd (2.4, 12.0,
14.4)
3.55 dd (12.0,
13.8)
2.35 dt (2.4,
13.8)
1
3
4
5
6
1
2
3
4
5
6
″
4.18 br q (3.0)
3.49 dd (3.0, 9.6)
4.01 dq (6.6, 9.6)
1.38 d (6.6)
68.0
73.6
74.8
18.7
4.12 br q (3.0)
3.52 d (3.6)
68.2
70.4
72.9
17.3
207.0 3.95 br s
79.9 3.24−3.34 m
66.8
73.2
″
4.09 d (9.6)
″
4.29 br q (6.6)
1.31 d (6.6)
3.60 qd (6.0, 9.6) 80.3
3.75 qd (6.0, 9.6) 72.3
″
1.48 d (6.0)
19.7
1.20 d (6.0)
5.05 d (7.8)
3.24−3.34 m
3.18 t (10.5)
3.24−3.34 m
3.40 m
18.6
99.9
76.5
69.6
73.1
77.1
60.6
‴
‴
‴
‴
‴
‴
3.47 m
3
.68 dd (1.8,
1.4)
1
a
Measured at 600 MHz for H NMR and 150 MHz for 13C NMR. Measured in acetone-d . Measured in DMSO-d .
1
b
c
6
6
moiety was deduced by 1H and 13C NMR and NOE
experiments. In the HMBC spectrum, cross-peaks of 5-OH/
C5, C-6, C-10; H-6/C-5, C-7, C-8, C-10; and H-1″/C-7, C-8
indicated that the sugar moiety was attached to C-8 via a C−C
linkage. A similar apigenin C-glycoside, torosaflavone A, has
The signals of H-3″, H-5″, and H-6″ were enhanced by
irradiation of H-4″, which suggested that H-4″ was in an
equatorial position. Thus, the 2,6-dideoxyhexosyl moiety was
deduced to be boivinopyranose. Its linkage to C-8 was
confirmed by the HMBC correlations of H-1″/C-7, C-8; 5-
OH/C-5, C-6, C-10; and H-6/C-5, C-7, C-8, C-10. On the
basis of the above evidence, the structure of compound 2 was
assigned as 8-C-β-D-boivinopyranosylapigenin.
1
4,15
16
been isolated from Drymaria diandra
and Cassia torosa;
however, its sugar moiety was linked to C-6 instead of C-8. On
the basis of the above NMR analysis, the structure of
compound 1 was determined as 8-C-β-D-digitoxopyranosylapi-
genin and was named 7-de-O-methylaciculatin.
The molecular formula of 3 was deduced as C22
H
O
by
C NMR spectra showed a
monosubstituted apigenin moiety like aciculatin and a sugar
moiety that possessed a carbonyl carbon (δ 207.0). In the
HMBC spectrum, the cross-peaks of 5-OH/C-5, C-6, C-10; H-
6/C-5, C-7, C-8, C-10; and 7-OCH /C-7 revealed that the
20
8
1
13
HREIMS. Its H and
Compound 2 was obtained as light yellow prisms and gave
1
the same molecular formula as 1 according to HREIMS. Its H
C
13
and C NMR spectra were similar to those of 1 except for the
1
signals arising from the 2,6-dideoxyhexosyl moiety. In the H
3
NMR spectrum, the anomeric proton H-1″ of the 2,6-
dideoxyhexosyl moiety showed a signal at δ 5.77 (dd, J = 2.4,
methoxy group was attached to C-7. Furthermore, the HMBC
correlations of H-1″ (δ 5.40) to C-7, C-8, and C-9 indicated
that the sugar moiety was attached to C-8 with a C−C linkage.
The carbonyl signal at δ 207.0 exhibited HMBC correlations
with H-2″, H-4″, and H-5″, suggesting the position of the
carbonyl group at C-3″. Moreover, the coupling constant (J =
9.6 Hz) of H-4″ and H-5″ indicated that these two protons had
trans-diaxial orientations. Thus, the structure was established as
3 and was named aciculatinone.
12.0 Hz), in which the large coupling constant indicated the
axial orientation of H-1″ and β-linkage of the sugar moiety to
the flavone. Furthermore, the coupling pattern of H-3″ (br q, J
=
3.0 Hz) suggested the equatorial orientation of H-3″. The
relative configuration of the 2,6-deoxyhexopyranose moiety was
determined by NOE experiments. The enhancement of H-1″ by
irradiation of H-5″ indicated that H-5″ was in an axial position.
1
99
dx.doi.org/10.1021/np2007796 | J. Nat. Prod. 2012, 75, 198−201

Journal of Natural Products
Article
Avatar 320 FT-IR spectrometer. H, 13C, and 2D NMR spectra were
recorded on a Varian VNMRS 600 MHz spectrometer. EIMS and
HRMS were obtained on Finnigan MAT GCQ and JEOL JMS-700
spectrometers, respectively. Silica gel 60 (Merck, 230−400 mesh),
Sephadex LH-20 (Amersham Biosciences, Sweden), and Cosmosil
C -OPN (Nacalai Tesque, Kyoto Japan) were used for purification. β-
1
Compound 4 had the molecular formula C H O as
determined from its HRFABMS. Its H and C NMR spectra
28
33 13
1
13
exhibited the typical resonances of a substituted apigenin
moiety. The 13C NMR spectrum showed signals similar to
those of aciculatin except for six more signals, at δ 60.6, 69.6,
3.1, 76.5, 77.1, and 99.9, attributed to a glucose moiety. In the
18
7
Glucosidase from almond (Nacalai Tesque, Kyoto Japan) was used for
the hydrolysis of compound 4.
Plant Material. The whole grass C. aciculatis was collected in
Taipei, Taiwan, in August 2006, and was authenticated by Professor
Ching-Hsiang Hsieh, Department of Plant Industry, National Pingtung
University of Science and Technology (NPUST). A voucher specimen
No.70652) was deposited in PPI Herbarium of NPUST.
Extraction and Isolation. The whole herb C. aciculatis (5.5 kg)
was heated under reflux with 95% EtOH (40 L) for one hour. After
filtration, the EtOH solution was concentrated in vacuo to provide a
dark brown EtOH extract (462 g). The EtOH extract was partitioned
with H O/EtOAc (1:1) to give EtOAc and H O layers. The EtOAc
1
H NMR spectrum, two anomeric protons appeared at δ 5.05
H
(
1H, d, J = 7.8 Hz, H-1‴) and 5.44 (1H, dd, J = 2.0, 12.0 Hz,
H-1″), which correlated, respectively, with carbons resonating at
δ 99.9 (C-1‴) and 64.9 (C-1″) in the HMQC spectrum. The
C
coupling constants of the anomeric protons indicated that each
sugar moiety was connected to the flavone via a β-linkage.
Enzymatic hydrolysis of 4 with β-glucosidase gave aciculatin
and glucose, suggesting that glucose was attached to the flavone
through a C−O bond. A positive optical rotation for the
isolated glucose indicated that it was β-D-glucose. In the HMBC
spectrum, the cross-peaks of 5-OH/C-5, C-6, C-10; H-6/C-5,
C-7, C-8, C-10; and H-1″/C-7, C-8, C-9 revealed that the
digitoxosyl moiety was attached to C-8 through a C−C linkage.
(
2
2
layer was concentrated to afford an EtOAc extract (80.8 g). The H O
layer was further partitioned with n-BuOH to give n-BuOH and H O
2
2
layers. The n-BuOH layer was concentrated to yield an n-BuOH
extract (48.4 g). The EtOAc extract was chromatographed on a silica
gel column (11 × 60 cm) eluted with a stepwise gradient system of n-
hexane/EtOAc (15:1; 10:1; 5:1; 1:1; 1:2; 0:1) to give six fractions (I−
VI). Fraction IV (eluted with n-hexane/EtOAc, 1:1) was rechromato-
graphed on a Sephadex LH-20 column eluted with MeOH to afford
kaempferol (2.6 mg). Fraction V (eluted with n-hexane/EtOAc, 1:2)
was subjected to a Sephadex LH-20 column eluted with MeOH to
provide three subfractions (Va−Vc). Fraction Va was chromato-
On irradiation at δ 5.05 (H-1‴), an NOE enhancement was
H
observed for the signal at δ 7.19 (H-3′ and H-5′), indicating
H
that the β-O-D-glucosyl moiety was linked to C-4′ via an ether
linkage. This linkage was further confirmed by the HMBC
correlation of H-1‴ to C-4′. Thus, compound 4 was elucidated
to be 8-C-β-D-digitoxopyranosyl-4′-O-β-D-glucopyranosylapige-
nin.
Compound 5 was obtained as light yellow prisms and gave
graphed on silica gel with CHCl /MeOH (20:1) as the eluent and
3
the molecular formula C H O according to HREIMS. The
1
6
10
6
Sephadex LH-20 with MeOH to give 3 (18.2 mg). Fraction Vb was
subjected to Sephadex LH-20 and silica gel columns eluted with
1
13
H and C NMR spectra showed a monosubstituted apigenin
moiety and a formyl group (δH 10.38 and δC 188.3). The
HMBC cross-peaks of H-1″/C-7, C-9 and H-6/C-5, C-7, C-8,
C-10 indicated that the formyl group was attached to C-8.
Thus, compound 5 was identified as apigenin-8-carbaldehyde,
which was previously obtained by oxidation of vitexin with
sodium periodate and here isolated from nature for the first
time.
Some of the isolates were evaluated for cytotoxic activity
against human cancer cell lines (Table 2). Aciculatin, 1, 2, and
MeOH and CHCl /MeOH (10:1), respectively, to afford tricin (2.8
mg) and taxifolin (8.1 mg). Fraction Vc was purified by a Sephadex
LH-20 column eluted with MeOH and a silica gel column eluted with
3
CHCl /MeOH (7:1) to yield 6,7,4′-trihydroxyflavone (1.3 mg) and
3
trans-oxyresveratrol (3.8 mg). Fraction VI (eluted with EtOAc) was
further separated on a Sephadex LH-20 column eluted with MeOH to
afford aciculatin (652.0 mg) and a subfraction, VIa. Fraction VIa was
12
subjected to a silica gel column eluted with CHCl /MeOH (10:1) and
3
a C -OPN column eluted with H O/MeOH (7:3) to give 1 (67.8
18
2
mg) and 2 (44.9 mg). The n-BuOH extract was separated with a
Sephadex LH-20 column eluted with MeOH to give five fractions
(VII−XI). Fraction VIII was chromatographed on a C -OPN column
Table 2. Cytotoxicity of Isolated Compounds against Four
Human Cell Lines
18
eluted with H O/MeOH (7:3) to afford 4 (1.72 g) and 5 (2.5 mg).
2
Luteolin-7-sulfate (9.0 mg) was obtained from fraction XI through a
Sephadex LH-20 column eluted with MeOH.
cell line (IC50 values in μM)
a
b
c
d
compound
MCF-7
H460
HT-29
CEM
7-De-O-methylaciculatin (8-C-β-D-digitoxopyranosylapige-
nin, 1): light yellow powder, mp 188−190 °C (3:1 CH OH/H O);
3
2
aciculatin
3.16
6.35
46.94
18.25
11.96
18.06
25.98
25.29
10.00
11.59
2.65
4.42
[
α] +79 (c 0.54, MeOH); UV (MeOH) λ (log ε) 331 (4.31), 271
D max
1
(
1
4.31), 213 (4.55) nm; IR (KBr) ν 3500, 1659, 1611, 1576, 1544,
max
2
74.98
18.36
2.58
−1
1
13
449, 1354, 1243, 1176 cm ; H and C NMR data, see Table 1;
3
13.33
+
EIMS m/z 400 [M] (14), 382 (21), 307 (87), 284 (31), 270 (100),
2
+
4
>100
2.50
>100
>100
6.04
>100
3.14
56 (60), 189 (36); HREIMS m/z [M] 400.1161 (calcd for
doxorubicin
6.06
C H O , 400.1164).
21
20
8
a
b
8
-C-β-D-Boivinopyranosylapigenin (2): light yellow prisms, mp
MCF-7: human breast cancer cells. H460: human lung cancer cells.
c
d
2
(
(
05−207 °C (3:1 CH OH/H O); [α] +85 (c 0.20, MeOH); UV
MeOH) λ (log ε) 333 (4.31), 271 (4.29), 212 (4.54) nm; IR
HT-29: human colon cancer cells. CEM: human leukemia cells.
3
2
D
max
KBr) ν 3400, 1659, 1611, 1580, 1544, 1449, 1354, 1239, 1176
3
showed differential potency on different cancer cell lines.
Noticeably, aciculatin and 1 indicated specificity of cytotoxicity
on MCF-7 and CEM cell lines.
max
−1
1
13
+
cm ; H and C NMR data, see Table 1; EIMS m/z 400 [M] (5),
82 (15), 307 (100), 284 (36), 270 (85), 256 (39), 189 (50);
3
+
HREIMS m/z [M] 400.1165 (calcd for C H O , 400.1172).
21
20
8
Aciculatinone (3): light yellow prisms, mp 146−148 °C (3:1
CH OH/H O); [α] +62 (c 0.27, MeOH); UV (MeOH) λmax (log ε)
335 (4.31), 268 (4.15), 214 (4.36) nm; IR (KBr) νmax 3500, 1718,
EXPERIMENTAL SECTION
General Experimental Procedures. Melting points were
determined on a Yanaco MP-I3 micro melting point apparatus and
are uncorrected. Optical rotations were recorded with a JASCO DIP-
70 digital polarimeter. UV spectra were measured on a Hitachi U-
310 spectrophotometer. IR spectra were recorded on a Nicolet
■
3
2
D
−1
1
13
1651, 1603, 1500, 1455, 1362, 1243, 1180 cm ; H and C NMR
+
data, see Table 1; EIMS m/z 412 [M] (42), 367 (15), 325 (23), 296
+
3
3
(42), 295 (45), 117 (90), 58 (100); HREIMS m/z [M] 412.1152
(calcd for C H O , 412.1146).
22
20
8
2
00
dx.doi.org/10.1021/np2007796 | J. Nat. Prod. 2012, 75, 198−201

Journal of Natural Products
Article
4
′-O-Glucosylaciculatin (4): light yellow prisms, mp 173−175 °C
(8) Huang, K. S.; Wang, Y. H.; Li, R. L.; Lin, M. J. Nat. Prod. 2000,
63, 86−89.
(
(
1
2:1 CH OH/H O); [α] −10 (c 0.20, MeOH); UV (MeOH) λ
log ε) 315 (4.21), 271 (4.29), 214 (4.48) nm; IR (KBr) ν 3500,
659, 1603, 1497, 1437, 1378, 1239, 1073 cm ; H and C NMR
data, see Table 1; FABMS m/z 577 [M + H] (10), 460 (10), 338
21), 307 (60), 289 (40), 154 (100); HRFABMS m/z [M + H]
77.1937 (calcd for C H O , 577.1938).
Apigenin-8-carbaldehyde (5): light brown prisms, mp 273−275
C (2:1 CH OH/H O); UV (MeOH) λ (log ε) 333 (3.96), 251
4.00), 231 (4.00) nm; IR (KBr) ν 3450, 1667, 1611, 1564, 1508,
441, 1374, 1287, 1243, 1180 cm ; H and C NMR data, see Table
; EIMS m/z 298 [M] (100), 270 (6), 178 (23), 118 (19); HREIMS
m/z [M] 298.0471 (calcd for C H O , 298.0477).
Enzymatic Hydrolysis of 4. Compound 4 (20 mg) and β-
glucosidase (10 mg) were dissolved in H O (15 mL), and the solution
was allowed to stand at 37 °C for 24 h. After addition of H O (10
3
2
D
max
(9) Wang, P. H.; Lee, S. S. J. Chin. Chem. Soc. (Taipei) 1999, 46,
215−219.
max
−1 1
13
+
(10) Williams, R. D.; Fawzi, A.; Lahlou, E. H. Patent WO
2007038875, 2007.
+
(
5
28
33 13
(11) Su, B. N.; Cuendet, M.; Hawthorne, M. E.; Kardono, L. B. S.;
Riswan, S.; Fong, H. H. S.; Mehta, R. G.; Pezzuto, J. M.; Kinghorn, A.
D. J. Nat. Prod. 2002, 65, 163−169.
°
(
1
1
3
2
max
max
(12) Evans, W. H.; McGookin, A.; Robertson, J. A.; Williamson, W.
R. N. J. Chem. Soc. 1957, 3510−3523.
−1
1
13
+
(13) Barron, D.; Ibrahim, R. K. Tetrahedron 1987, 43, 5197−5202.
(14) Ding, Z. T.; Yang, X. Q.; Cao, Q. E.; Li, F. J. Integr. Plant Biol.
2005, 47, 1140−1144.
+
16
10
6
2
(15) Hsieh, P. W.; Chang, F. R.; Lee, K. H.; Hwang, T. L.; Chang, S.
M.; Wu, Y. C. J. Nat. Prod. 2004, 67, 1175−1177.
2
mL), the reaction mixture was extracted with EtOAc. The EtOAc
extract was concentrated in vacuo to give aciculatin (10 mg), which
showed NMR spectral data identical with those of the authentic
sample. The aqueous layer was concentrated and then chromato-
graphed on a silica gel column eluted with CH CN/H O (8:1) to
afford D-glucose (4 mg), which showed a specific rotation of +21.1 (c
(16) Kitanaka, S.; Ogata, K.; Takido, M. Chem. Pharm. Bull. 1989, 37,
2
(
441−2444.
17) Roslund, M. U.; Tahtinen, P.; Niemitz, M.; Sjoholm, R.
Carbohydr. Res. 2008, 343, 101−112.
(18) Cheng, J. J.; Zhang, L. J.; Cheng.; Cheng, H. L.; Chiou, C. T.;
Lee, I. J.; Kuo, Y. H. J. Nat. Prod. 2010, 73, 1655−1658.
3
2
0
.54, H O). Its NMR data were essentially identical with those
reported in the literature, and the retention factor (R = 0.24) in
2
17
f
TLC was the same as that of the authentic sugar with CH CN/H O
3
2
(
6:1) as the solvent system.
Cytotoxic Assay. Four human cancer cell lines, MCF-7 (breast
cancer), H-460 (lung cancer), HT-29 (colon cancer), and CEM
leukemia), were obtained from the Bioresources Collection and
(
Research Center (BCRC), Hsin-Chu, Taiwan. Some of the isolates
were evaluated for cytotoxic activity using a previously described
18
protocol. Doxorubicin was used as a positive control.
ASSOCIATED CONTENT
■
*
S
Supporting Information
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
■
*
Corresponding Author
Tel: 886-4-26318652, ext 5601. E-mail: ccchen@sunrise.hk.
edu.tw.
ACKNOWLEDGMENTS
■
We thank the National Center for High-Performance
Computing, Taipei, Taiwan, for computer time and facilities.
This research was supported by the National Science Council
of the Republic of China (NSC 98-2320-B-241-003-MY3).
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