Identification of antiadipogenic constituents of the rhizomes of Anemarrhena asphodeloides.
ABSTRACT Three new phenolic compounds, (E)-4'-demethyl-6-methyleucomin (1), anemarcoumarin A (2), and anemarchalconyn (3), were isolated from an ethyl acetate extract of the rhizomes of Anemarrhena asphodeloides, together with seven known compounds (4-10). The structures of the new compounds (1-3) were determined on the basis of spectroscopic data interpretation. Compound 3 exhibited a potent inhibitory effect against the differentiation of preadipocyte 3T3-L1 cells with an IC50 value of 5.3 microM.
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ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. Cholinesterase inhibitors are widely used for the symptomatic treatment of Alzheimer's disease to enhance central cholinergic transmission. In this study, a bioactivity-oriented screening platform based on a modified Ellman's method and HPLC-QTOF MS technique was developed to rapidly screen active agents of Anemarrhena asphodeloides Bge. The 60% ethanol fraction from an ethyl acetate extract exhibited the most potential anticholinesterase activity. Fifteen steroid saponins were identified by the mass spectrum, standards and literature reports. Twenty-five compounds were isolated from the active fraction. The results showed that compounds with the C6-C3-C6 skeleton probably had both AChE and BuChE inhibitory activities. Xanthone and benzene derivatives exhibited no or little activity. Lignans showed weak BuChE inhibitory activity. The steroidal saponins demonstrated moderate or weak AChE inhibitory activity.Evidence-based Complementary and Alternative Medicine 01/2014; 2014:524650. · 2.18 Impact Factor
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ABSTRACT: Anemarrhena asphodeloides Bunge. (Asparagaceae) yields Anemarrhenae Rhizoma, which has a long history to be used as a traditional medicine to treat various ailments, like cold-induced febrile disease with arthralgia, hematochezia, tidal fever and night sweats by Yin deficiency, bone-steaming, cough, and hemoptysis. It is also used as an ingredient of healthy food, wine, tea, biological toothpaste. Its importance is demonstrated by large scale to treat kinds of diseases in eastern Asian countries. The aim of this review is to provide up-to-date information about phytochemistry, pharmacology, and toxicology of Anemarrhena asphodeloides based on scientific literatures. It will build up a new foundation for further study on mechanism and development of better therapeutic agent and healthy product from Anemarrhena asphodeloides. All the available information on Anemarrhena asphodeloides was collected via electronic search (using PubMed, SciFinder Scholar, CNKI, TPL (www.theplantlist.org), Google Scholar, Baidu Scholar, and Web of Science). Comprehensive analysis of the literatures searched through sources available above confirmed that the ethnomedical uses of Anemarrhenaasphodeloides had been recorded in China, Japan, and Korea for thousands of years. The phytochemical investigation revealed the presence of steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, anthraquinones, and others. Crude extracts and pure compounds from Anemarrhenaasphodeloides exhibited significant pharmacological effects on the nervous system and the blood system. They also showed valuable bioactivities, such as antitumor, anti-oxidation, anti-microbial, anti-virus, anti-inflammation, anti-osteoporosis, anti-skin aging and damage as well as other activities. In light of long traditional use and modern phytochemical and pharmacological studies summarized, Anemarrhena asphodeloides has demonstrated a strong potential for therapeutic and health-maintaining purposes. Both the extracts and chemical components isolated from the plant showed a wide range of biological activities. Thus more pharmacological mechanisms on main active compounds (TBII, TAIII, mangiferin and other ingredients) are necessary to be explored. In addition, as a good source of the traditional medicine, clinical studies of main therapeutic aspects (e.g. diabetes, Alzheimer׳s disease, Parkinson׳s disease, etc.), toxicity and adverse effect of Anemarrhena asphodeloides will also undoubtedly be the focus of future investigation.Journal of ethnopharmacology 02/2014; · 2.32 Impact Factor
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ABSTRACT: An ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS) method was developed for metabolite profiling of Anemarrhena asphodeloides Bunge from two different geographical origins. In this study, the metabolite profile data obtained using UPLC-QTOF MS was subjected to multivariate statistical analyses, such as the principal component analysis and the hierarchical clustering analysis, to compare metabolite patterns among A. asphodeloides samples. Furthermore, a metabolite selection method known as significance analysis of microarrays (SAM) was applied to further select metabolites and to identify key constituents to efficiently distinguish between geographical origins. The UPLC-QTOF MS analysis successfully classified 21 samples into two distinct groups according to their geographical origins. The validation method used to assess the analytical stability and accuracy of these data is also described. These results suggest that this proposed method is reliable, accurate, and effective for geographic classification of A. asphodeloides, thus guiding its proper use for therapeutic purposes.Journal of pharmaceutical and biomedical analysis 01/2014; 92C:47-52. · 2.45 Impact Factor
Identification of Antiadipogenic Constituents of the Rhizomes of Anemarrhena asphodeloides
Ui Joung Youn,†Ye Seul Lee,†Hana Jeong,†Jun Lee,†,‡Joo-Won Nam,†Yoo Jin Lee,†Eun Sook Hwang,†Je-Hyun Lee,§
Dongho Lee,⊥Sam Sik Kang,|and Eun-Kyoung Seo*,†
The Center for Cell Signaling & Drug DiscoVery Research, College of Pharmacy, Ewha Womans UniVersity, Seoul 120-750, Korea, Diabetes
Research Center, DiVision of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM),
Daejeon 305-811, Korea, Department of Korean Medicine, Dongguk UniVersity, Geongju 780-714, Korea, School of Life Sciences and
Biotechnology, Korea UniVersity, Seoul 136-713, Korea, and College of Pharmacy, Seoul National UniVersity, Seoul 151-742, Korea
ReceiVed July 2, 2009
Three new phenolic compounds, (E)-4′-demethyl-6-methyleucomin (1), anemarcoumarin A (2), and anemarchalconyn
(3), were isolated from an ethyl acetate extract of the rhizomes of Anemarrhena asphodeloides, together with seven
known compounds (4-10). The structures of the new compounds (1-3) were determined on the basis of spectroscopic
data interpretation. Compound 3 exhibited a potent inhibitory effect against the differentiation of preadipocyte 3T3-L1
cells with an IC50value of 5.3 µM.
The rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae)
have been used as a traditional medicine for their anodyne,
antidiabetic, antiphlogistic, antipyretic, diuretic, and sedative
properties in Korea, mainland China, and Japan.1There have been
several phytochemical reports on this species concerning its
xanthones,2norlignans,3,4and steroidal saponins,5-7associated with
various biological activities such as antidiabetic,5anticancer,6
antioxidant,2antifungal,3,4and antidepressant effects.7
During a study to find novel adipocyte differentiation inhibitors
of plant origin, the EtOAc extract of the rhizomes of A. asphode-
loides exhibited an inhibitory effect against differentiation on
preadipocyte 3T3-L1 cells at a concentration level of 100 µg/mL.
The inhibitory activity of A. asphodeloides on adipocyte differentia-
tion has not been reported previously. Mouse preadipocyte 3T3-
L1 cells differentiate into mature adipocytes in the presence of
specific factors such as insulin, dexamethasone, and PAPRγ
activators, and they afford a well-known in vitro model system that
reflects adipose tissue formation in vivo.8,9Therefore, the EtOAc
fraction of A. asphodeloides was subjected to detailed phytochemi-
cal investigation, resulting in the isolation of three new phenolic
compounds (1-3), along with seven known compounds (4-10).
In the present study, the isolation and structure elucidation of 1-3
are reported as well as the evaluation of 1-10 for their inhibitory
effects against differentiation of preadipocyte 3T3-L1 cells.
Compound 1 was obtained as a yellow powder. Its molecular
formula was established as C17H14O5on the basis of the molecular
ion peak at m/z 299.0922 [M + H]+(calcd for C17H15O5, 299.0919)
in the positive high-resolution FABMS. The UV spectrum showed
an absorption maximum at 288 nm, indicating the presence of one
or more separate aromatic group(s). In the IR spectrum of 1,
absorption bands for one or more hydroxy group(s) and a carbonyl
functionality were observed at 3368 and 1730 cm-1, respectively.
The1H NMR spectrum of 1 (Table 1) showed two symmetrical
doublets at δ 6.87 (2H, J ) 8.4 Hz, H-3′ and H-5′) and 7.23 (2H,
J ) 8.4 Hz, H-2′ and H-6′), indicating the presence of a para-
substituted benzyl group. The1H and13C NMR signals for one
aromatic methine at δH5.88/δC95.1 (C-8), an oxygenated meth-
ylene at δH5.27 (2H, d, J ) 1.6 Hz)/δC68.6 (C-2), and a carbonyl
carbon at δC186.6 (C-4) were indicative of the presence of an
isoflavonoid skeleton. Besides these characteristics for the isofla-
vonoid skeleton, there was a benzylic methine signal at δH7.72
(H-7′), which correlated with C-2, C-4, and C-2′ and C-6′ in the
HMBC experiment of 1. Therefore, compound 1 could be assigned
with a benzylic methine group between C-3 and C-1′, thus
displaying a typical homoisoflavanoid skeleton. These data were
comparable with the known homoisoflavanone (E)-5,7-dihydroxy-
3-(4′-hydroxybenzylidene)chroman-4-one (9),10except for the
presence of a methyl group in 1. The configuration of the vinylic
proton was determined as trans (E) due to its typical chemical shift
value at δ 7.72 (1H, s, H-7′), which appeared relatively more
downfield than the cis Z-isomer (δ 7.02, s).11On the other hand,
additional NMR data of 1 obtained in DMSO-d6were used to solve
the position of the methyl group. Thus, a hydrogen-bonded hydroxy
proton appeared at δH13.18 (OH-5), which was correlated with
C-5, C-6, and C-4a in the HMBC experiment. The methyl group
resonated at δH1.86 in DMSO-d6and exhibited two- and three-
bond correlations with C-5, C-6, and C-7, indicating the position
of the methyl group to be C-6. As a result, 1 [(E)-4′-demethyl-6-
methyleucomin] was elucidated as the new compound (E)-5,7-
Compound 2 was obtained as a yellow powder. Its molecular
formula was established as C16H12O4from the molecular ion peak
at m/z 268.0738 [M]+(calcd for C16H12O4, 268.0735) in the
HREIMS. The IR spectrum showed the presence of a hydroxy group
at 3298 cm-1and a carbonyl group at 1690 cm-1. The1H NMR
spectrum of 2 showed the presence of a para-substituted benzene
group at δ 6.73 (2H, d, J ) 8.8 Hz) and 7.10 (2H, d, J ) 8.8 Hz)
and an ABX-type aromatic system at δ 6.68 (1H, d, J ) 2.0 Hz),
6.75 (1H, dd, J ) 2.0, 8.4 Hz), and 7.32 (1H, d, J ) 8.4 Hz). The
NMR signals at δH 7.45/δC 141.7 (C-4) and 164.3 (C-2) were
characteristic for a coumarin structure. A methylene functionality
resonated at δH3.69/δC36.5, which was correlated with C-2, C-3,
C-4, and C-2′ and C-6′ in the HMBC experiment of 2. These data
were comparable to the known synthetic compound 3-benzyl-7-
methoxychromen-2-one,12except for the presence of a hydroxy
group at C-7 in compound 2. Therefore, 2 (anemarcoumarin A)
was determined as the new compound 7-hydroxy-3-(4-hydroxy-
Compound 3 was obtained as a yellow powder, and its molecular
formula of C15H10O3was established from the molecular ion peak
at m/z 238.0630 [M]+(calcd for C15H10O3, 238.0630) in the
HREIMS. The IR absorption bands at 1620 and 2193 cm-1
suggested the presence of a carbonyl group and a CtC triple bond,
respectively.13The13C NMR signal at δC178.5 (C-1) supported
the presence of the carbonyl group, and the two quaternary carbons
* To whom correspondence should be addressed. Tel: +82-2-3277-3047.
Fax: +82-2-3277-3051. E-mail: firstname.lastname@example.org.
†Ewha Womans University.
‡Korea Institute of Oriental Medicine.
|Seoul National University.
J. Nat. Prod. 2009, 72, 1895–1898
10.1021/np900397f CCC: $40.75
2009 American Chemical Society and American Society of Pharmacognosy
Published on Web 09/17/2009
at δC87.2 and 95.7 indicated the occurrence of a triple bond. Two
sets of para-substituted aromatic groups resonated at δH6.90 (2H,
d, J ) 8.8 Hz, H-3′ and H-5′), 8.07 (2H, d, J ) 8.8 Hz, H-2′ and
H-6′), 6.85 (2H, d, J ) 8.8 Hz, H-3′′ and H-5′′), and 7.55 (2H, d,
J ) 8.8 Hz, H-2′′ and H-6′′). The position of the carbonyl group
was assigned at C-1 by the three-bond connectivity between the
carbonyl group and H-2′ and H-6′ of the HMBC spectrum. In turn,
the triple bond was positioned between C-2 and C-3 from the three-
bond connectivity between C-3 and H-2′ and H-6′ in the HMBC
spectrum of 3. These data for 3 were comparable to those of the
known synthetic compound 1,3-diphenylpropynone,14except for
the presence of two separate para-hydroxy groups at the two phenyl
groups in 3. Therefore, 3 (anemarchalconyn) was elucidated as the
new compound 1,3-bis(4-hydroxyphenyl)prop-2-yn-1-one.
The other seven isolates obtained were identified as the previ-
souly known compounds nyasol (4),154′-O-methylnyasol (5),162′-
13C NMR Spectroscopic Data for (E)-4′-Demethyl-6-methyleucomin (1), Anemarcoumarin A (2), and
δH, (J in Hz)
δH, (J in Hz)
δH, (J in Hz)
5.27, d (1.6)164.3, qC
7.32, d (8.4)
6.75, dd (8.4, 2.0)
5.88, s 6.68, d (2.0)
7.23, d (8.4)
6.87, d (8.4)
7.10, d (8.8)
6.73, d (8.8)
8.07, d (8.8)
6.90, d (8.8)
6.87, d (8.4)
7.23, d (8.4)
6.73, d (8.8)
7.10, d (8.8)
6.90, d (8.8)
8.07, d (8.8)
7.55, d (8.8)
6.85, d (8.8)
6.85, d (8.8)
7.55, d (8.8)
aSpectrum recorded at 400 MHz (1H NMR) and 100 MHz (13C NMR) in CD3OD.
Figure 1. Important HMBC and NOESY correlations of 1-3.
Journal of Natural Products, 2009, Vol. 72, No. 10 Notes
zophenone (7),18broussonin A (8),19(E)-5,7-dihydroxy-3-(4′-
hydroxybenzylidene)chroman-4-one (9),10and 2′,4′,4-trihydro-
xychalcone (10),20by comparison of their physical and spectro-
scopic data with published values. To the best of our knowledge,
compounds 6, 9, and 10 have been isolated from the genus
Anemarrhena for the first time.
Compounds 1-10 were tested in vitro for their inhibitiory effects
on the adipogenic differentiation of preadipocyte 3T3-L1 cells. Of
these, the new compound 3 exhibited a potent inhibitory effect with
an IC50value of 5.3 µM. Compounds 5, 6, 8, and 10 showed less
potent inhibitory activities, with IC50values of 45.9, 41.8, 74.5,
and 96.4 µM, respectively. Compounds 1, 4, and 9 had no
significant inhibition effects on adipogenic differentiation, while
compounds 2 and 7 could not be evaluated in this manner, due to
their insufficient amounts available for testing (Table 2).
General Experimental Procedures. Melting points were measured
using an Electrothermal apparatus. Optical rotations were measured
with a P-1010 polarimeter (JASCO, Japan) at 20 °C. UV and IR
spectra were recorded on a U-3000 spectrophotometer (Hitachi,
Japan) and a FTS 135 FT-IR spectrometer (Bio-Rad, CA), respec-
tively. 1D and 2D NMR experiments were performed on a UNITY
INOVA 400 MHz FT-NMR instrument (Varian, CA) with tetram-
ethylsilane (TMS) as internal standard. Mass spectrometry was
carried out with a JEOL JMS-700 Mstation mass spectrometer. Thin-
layer chromatography (TLC) was performed on precoated silica gel
60 F254 (0.25 mm, Merck). Silica gel (230-400 mesh, Merck,
Germany) and RP-18 (YMC gel ODS-A, 12 nm, S-150 µm) were
used for column chromatography. Preparative HPLC was run on an
Acme 9000 HPLC (Young Lin, South Korea) using a YMC-pack
ODS-A column, with a the flow rate of 1 mL/min.
Plant Material. The rhizomes of A. asphodeloides were purchased
from Oriental Herb Store (OmniHerb.com) in Seoul, South Korea,
in September 2008, and were identified by one of the authors (J.-
H.L.). A voucher specimen (no. EA270) was deposited at the Natural
Product Chemistry Laboratory, College of Pharmacy, Ewha Womans
Extraction and Isolation. The rhizomes of A. asphodeloides (20
kg) were extracted with MeOH three times under reflux for 4 h.
The MeOH solutions were concentrated in vacuo to yield a dried
MeOH-soluble extract (4 kg). This extract was suspended in distilled
water and fractionated with n-hexane, EtOAc, and n-BuOH, suc-
cessively. The active EtOAc extract (75 g) was chromatographed
over a silica gel (1875 g) column, eluting with a gradient solvent
system of n-hexane-EtOAc (100:1 to 1:1), to afford 25 fractions
(E1-E25). Fraction E8 (10.0 g) was chromatographed on a silica
gel (250 g) column eluting with CHCl3-MeOH (100:1 to 10:1) to
afford five subfractions (E8.1 to E8.5). Subfraction E8.3 (5.1 g)
was chromatographed on a silica gel (125 g) column using
CHCl3-MeOH (50:1 to 10:1) to give five subfractions (E8.3.1 to
E8.3.5). Subfraction E8.3.2 (0.2 g) was subjected to semipreparative
HPLC (MeOH-H2O, 75:25 to 90:10] to yield compound 5 [15 mg
(0.000375% w/w), tR 120 min]. Fraction E8.3.3 (3.5 g) was
n-hexane-EtOAc (100:1 to 50:50) as gradient solvent system to
afford compounds 4 (1500 mg, 0.375% w/w) and 8 (10 mg,
0.00025% w/w), which were eluted with 80:20 and 60:40
n-hexane-EtOAc, respectively. Fraction E11 (3.0 g) was chromato-
graphed on a silica gel (75 g) column eluting with CHCl3-MeOH
(50:1 to 5:1) to afford 20 subfractions (E11.1 to E11.20). Subfraction
E11.16(0.2 g) was subjected
(MeOH-H2O, 75:25) to yield compounds 1 [5 mg (0.000125% w/w),
tR125 min], 9 [4 mg (0.0001% w/w), tR115 min], and 10 [8 mg
(0.0002% w/w), tR90 min]. Fraction E14 (5.0 g) was chromato-
graphed on a silica gel (125 g) column, using a gradient solvent
system of CHCl3-MeOH (50:1 to 5:1), to give compounds 6 [5 mg
(0.000125% w/w)] and 7 [1500 mg (0.375% w/w)], which were
eluted with 40:1 and 30:1 CHCl3-MeOH, respectively. Fraction E22
(4.0 g) was chromatographed on a silica gel (100 g) column, eluted
with CHCl3-MeOH (50:1 to 5:1), to afford nine subfractions (E22.1
to E22.9). Subfraction E22.5 (0.1 g) was further purified by
semipreparative HPLC (MeOH-H2O, 40:60) to yield compound 2
[2 mg (0.00005% w/w), tR150 min]. Subfraction E22.6 (0.05 g)
was subjected to HPLC (MeOH-H2O, 40:60) to yield compound 3
[1.5 mg (0.0000375% w/w), tR180 min].
(E)-4′-Demethyl-6-methyleucomin (1): yellow powder; UV (MeOH)
λmax (log ε) 349 (3.7), 288 (3.8) nm; IR νmax (KBr) 3368, 2913,
1730, 1595, 1467 cm-1;1H (400 MHz) and13C NMR (100 MHz)
data (in CD3OD), see Table 1;1H NMR (400 MHz, DMSO-d6) δ
5.27 (2H, s, H-2), 5.84 (1H, brs, H-8), 6.85 (2H, d, J ) 8.8 Hz,
H-3′, 5′), 7.29 (2H, d, J ) 8.8 Hz, H-2′, 6′), 7.62 (1H, brs, H-7′),
1.86 (3H, s, CH3-6), 13.18 (1H, brs, OH-5);13C NMR (100 MHz,
DMSO-d6) δ 66.9 (CH2, C-2), 126.7 (C, C-3), 183.4 (C, C-4), 101.0
(C, C-4a), 161.5 (C, C-5), 103.7 (C, C-6), 166.1 (C, C-7), 94.4 (CH,
C-8), 159.3 (C, C-8a), 124.9 (C, C-1′), 132.6 (CH, C-2′, 6′), 115.7
(CH, C-3′, 5′), 159.3 (C, C-4′), 135.7 (CH, C-7′); HRFABMS m/z
299.0922 [M + H]+(calcd for C17H15O5, 299.0919).
Anemarcoumarin A (2): yellow powder; UV (MeOH) λmax(log
ε) 320 (3.9), 250 (3.7) nm; IR νmax(KBr) 3298, 2918, 1690, 1610,
1454 cm-1;1H (400 MHz) and13C NMR (100 MHz) data, see Table
1; HREIMS m/z 268.0738 [M]+(calcd for C16H12O4, 268.0735).
Anemarchalconyn (3): yellow powder; UV (MeOH) λmax(log ε)
286 (4.2) nm; IR νmax(KBr) 3350, 2193, 1620, 1159 cm-1;1H (400
MHz) and13C NMR (100 MHz) data, see Table 1; HREIMS m/z
238.0630 [M]+(calcd for C15H10O3, 238.0630).
Differentiation of 3T3-L1 Preadipocytes. 3T3-L1 preadipocytes
were maintained in Dulbecco’s modified Eagle’s medium (DMEM)
supplemented with 10% calf serum. For adipocyte differentiation,
cells were grown to confluence for 48 h and the medium was changed
to DMEM containing insulin (5 µg/mL), 10 µM rosiglitazone, 1
µM dexamethasone, and 10% fetal bovine serum (FBS), to dif-
ferentiate adipocytes (day 0). Cells were then replaced with 10%
FBS/DMEM supplemented with 5 µg/mL insulin after 48 h and
refreshed with 10% FBS/DMEM every other day during differentia-
tion. In order to observe the effect of compounds on adipocyte
differentiation, cells were treated with the indicated amounts of
compounds on differentiation day 0, refreshed every 2 days, and
stained with Oil-red O at day 7.
Oil-red O Staining. At differentiation day 7, cells were washed
with phosphate-buffered saline (PBS) and fixed in 10% formalin
for 10 min. Cells were subsequently rinsed twice with PBS and
stained with Oil-red O staining solution for 1 h at room temperature.
Stained cells were washed with distilled water and dissolved in 100%
isopropyl alcohol for measuring the absorbance at 500 nm.
Acknowledgment. This research was supported by the Korea Food
and Drug Administration (08182 Crude Drugs 258). The work was
also funded in part by a grant from the Brain Korea 21 program
and in part by the NCRC program of MOST/KOSEF (R15-2006-
020-00000-0) through the Center for Cell Signaling & Drug
Discovery Research at Ewha Womans University.
Supporting Information Available: Spectroscopic data including
1H and13C NMR, 2D NMR, and HRMS of new compounds 1-3.
This information is available free of charge via the Internet at http://
References and Notes
(1) Duke, J. A. Handbook of Medicinal Herbs, 2nd ed.; CRC Press: New
York, 2002; pp 27-28.
(2) Pardo-Andreu, G. L.; Sanchez-Baldoquin, C.; Avila-Gonzalez, R.;
Delgado, R.; Naal, Z.; Curti, C. Eur. J. Pharmacol. 2006, 547, 31–
(3) Iida, Y.; Oh, K. B.; Saito, M.; Matsuoka, H.; Kurata, H. Planta Med.
2000, 66, 435–438.
Table 2. Inhibitory Activities of Compounds 1-10 on Differentiation of Preadipocyte 3T3-L1 Cells
aIC50values of greater than 100 µM are considered to be inactive.bNot determined.cPositive control substance.
NotesJournal of Natural Products, 2009, Vol. 72, No. 10 1897
(4) Park, H. J.; Lee, J. Y.; Moon, S. S.; Hwang, B. K. Phytochemistry
2003, 64, 997–1001.
(5) Nakashima, N.; Kimura, I.; Kimura, M. J. Nat. Prod. 1993, 56, 345–
(6) Sy, L. K.; Yan, S.-C.; Lok, C.-N.; Man, R. Y. K.; Che, C.-M. Cancer
Res. 2008, 68, 10229–10237.
(7) Ren, L.-X.; Luo, Y.-F.; Li, X.; Zuo, D.-Y.; Wu, Y.-L. Biol. Pharm.
Bull. 2006, 29, 2304–2306.
(8) Green, H.; Kehinde, O. Cell 1975, 5, 19–27.
(9) Green, H.; Kehinde, O. Cell 1976, 7, 105–113.
(10) Silayo, A.; Ngadjui, B. T.; Abegaz, B. M. Phytochemistry 1999, 52,
(11) Chen, P.; Yang, J.-S. Chem. Pharm. Bull. 2007, 55, 655–657.
(12) Torang, J.; Vanderheiden, S.; Nieger, M.; Brase, S. Eur. J. Org. Chem.
2007, 6, 943–952.
(13) DePinto, J. T.; deProphetis, W. A.; Menke, J. L.; McMahon, R. J.
J. Am. Chem. Soc. 2007, 129, 2308–2315.
(14) Vasil’ev, A. V.; Walspurger, S.; Pale, P.; Sommer, J.; Haouas, M.;
Rudenko, A. P. Russ. J. Org. Chem. 2004, 40, 1769–1778.
(15) Minami, E.; Taki, M.; Takaishi, S.; Iijima, Y.; Tsutsumi, S.; Akiyama,
T. Chem. Pharm. Bull. 2000, 48, 389–392.
(16) Sun, Q.; Sun, A.; Liu, R. J. Chromatogr. A 2006, 1104, 69–74.
(17) Yahara, S.; Ogata, T.; Saijo, R.; Konishi, R.; Yamahara, J.; Miyahara,
K.; Nohara, T. Chem. Pharm. Bull. 1989, 37, 979–987.
(18) Matsuda, H.; Sato, N.; Yamazaki, M.; Naruto, S.; Kubo, M. Biol.
Pharm. Bull. 2001, 24, 586–587.
(19) Takasugi, M.; Anetai, M.; Masamune, T.; Shirata, A.; Takahashi, K.
Chem. Lett. 1980, 3, 339–340.
(20) Abd El-Hafiz, M. A.; Ramadan, M. A.; Anton, R. J. Nat. Prod. 1990,
Journal of Natural Products, 2009, Vol. 72, No. 10 Notes