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EDITORS
PROFESSOR ALEJANDRO F. BARRERO
Department of Organic Chemistry, University of Granada,
Campus de Fuente Nueva, s/n, 18071, Granada, Spain
afbarre@ugr.es
PROFESSOR ALESSANDRA BRACA
Dipartimento di Chimica Bioorganicae Biofarmacia,
Universita di Pisa,
via Bonanno 33, 56126 Pisa, Italy
braca@farm.unipi.it
PROFESSOR DE-AN GUO
National Engineering Laboratory for TCM Standardization Technology,
Shanghai Institute of Materia Medica, Chinese Academy of Sciences,
Shanghai 201203, P. R. China
gda5958@163.com
PROFESSOR VLADIMIR I. KALININ
G.B. Elyakov Pacific Institute of Bioorganic Chemistry,
Far Eastern Branch, Russian Academy of Sciences,
Pr. 100-letya Vladivostoka 159, 690022,
Vladivostok, Russian Federation
PROFESSOR YOSHIHIRO MIMAKI
School of Pharmacy,
Tokyo University of Pharmacy and Life Sciences,
Horinouchi 1432-1, Hachioji, Tokyo 192-0392, Japan
mimakiy@ps.toyaku.ac.jp
PROFESSOR STEPHEN G. PYNE
Department of Chemistry, University of Wollongong,
Wollongong, New South Wales, 2522, Australia
spyne@uow.edu.au
PROFESSOR MANFRED G. REINECKE
Department of Chemistry, Texas Christian University,
Forts Worth, TX 76129, USA
m.reinecke@tcu.edu
PROFESSOR WILLIAM N. SETZER
Department of Chemistry, The University of Alabama in Huntsville,
Huntsville, AL 35809, USA
wsetzer@chemistry.uah.edu
PROFESSOR YASUHIRO TEZUKA
Faculty of Pharmaceutical Sciences, Hokuriku University,
Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan
y-tezuka@hokuriku-u.ac.jp
PROFESSOR DAVID E. THURSTON
Institute of Pharmaceutical Science
Faculty of Life Sciences & Medicine
King’s College London, Britannia House
7 Trinity Street, London SE1 1DB, UK
david.thurston@kcl.ac.uk
ADVISORY BOARD
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Karachi, Pakistan
Prof. Giovanni Appendino
Novara, Italy
Prof. Yoshinori Asakawa
Tokushima, Japan
Prof. Roberto G. S. Berlinck
São Carlos, Brazil
Prof. Anna R. Bilia
Florence, Italy
Prof. Maurizio Bruno
Palermo, Italy
Prof. Josep Coll
Barcelona, Spain
Prof. Geoffrey Cordell
Chicago, IL, USA
Prof. Fatih Demirci
Eskişehir, Turkey
Prof. Francesco Epifano
Chieti Scalo, Italy
Prof. Ana Cristina Figueiredo
Lisbon, Portugal
Prof. Cristina Gracia-Viguera
Murcia, Spain
Dr. Christopher Gray
Saint John, NB, Canada
Prof. Dominique Guillaume
Reims, France
Prof. Duvvuru Gunasekar
Tirupati, India
Prof. Hisahiro Hagiwara
Niigata, Japan
Prof. Judith Hohmann
Szeged, Hungary
Prof. Tsukasa Iwashina
Tsukuba, Japan
Prof. Leopold Jirovetz
Vienna, Austria
Prof. Phan Van Kiem
Hanoi, Vietnam
Prof. Niel A. Koorbanally
Durban, South Africa
Prof. Chiaki Kuroda
Tokyo, Japan
Prof. Hartmut Laatsch
Gottingen, Germany
Prof. Marie Lacaille-Dubois
Dijon, France
Prof. Shoei-Sheng Lee
Taipei, Taiwan
Prof. Imre Mathe
Szeged, Hungary
Prof. M. Soledade C. Pedras
Saskatoon, Canada
Prof. Luc Pieters
Antwerp, Belgium
Prof. Peter Proksch
Düsseldorf, Germany
Prof. Phila Raharivelomanana
Tahiti, French Polynesia
Prof. Luca Rastrelli
Fisciano, Italy
Prof. Stefano Serra
Milano, Italy
Dr. Bikram Singh
Palampur, India
Prof. John L. Sorensen
Manitoba, Canada
Prof. Johannes van Staden
Scottsville, South Africa
Prof. Valentin Stonik
Vladivostok, Russia
Prof.Ping-Jyun Sung
Pingtung, Taiwan
Prof. Winston F. Tinto
Barbados, West Indies
Prof. Sylvia Urban
Melbourne, Australia
Prof. Karen Valant-Vetschera
Vienna, Austria
HONORARY EDITOR
PROFESSOR GERALD BLUNDEN
The School of Pharmacy & Biomedical Sciences,
University of Portsmouth,
Portsmouth, PO1 2DT U.K.
axuf64@dsl.pipex.com
Acetophenones Isolated from Acronychia pedunculata and their
Anti-proliferative Activities
Chihiro Ito
a
, Takuya Matsui
b
, Yoshiaki Ban
a
, Tian-Shung Wu
c
and Masataka Itoigawa
d,*
a
Department of Medicinal Chemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku,
Nagoya 468-8503, Japan
b
Department of Physiology, Aichi Medical University, Yazako-karimata 1-1, Nagakute, Aichi 480-1195, Japan
c
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan
d
School of Sport and Health Science, Tokai Gakuen University, 21-233 Nishinohora, Ukigai, Miyoshi,
Aichi 470-0207, Japan
itoigawa@tokaigakuen-u.ac.jp
Received: September 13
th
, 2015; Accepted: October 29
th
, 2015
Study of the chemical constituents of Acronychia pedunculata (L.) Miq. (Rutaceae) stems collected in Taiwan led to the isolation and identification of eight
known and three new acetophenones, named acrophenone A (1), B (2), and C (3). Of them, acrovestone (5), acropyrone (6) and acrovestenol (7) , which are
dimer compounds, strikingly inhibited the proliferation of human leukemia cell lines.
Keywords: Acronychia pedunculata, Rutaceae, Acetophenone, Antiproliferative effects.
The genus Acronychia (Rutaceae) is distributed from India to
southern China, and the roots, stems, leaves, and fruits of A.
pedunculata (L.) Miq. have been used in folk medicine to treat
various diseases such as asthma, diarrhea, rheumatism, sores,
swellings, pain and itchy skin [1]. A. pedunculata is a rich source of
prenylated acetophenone derivatives [2] that exhibit biological
effects such as antioxidant
[3a], cytotoxic [3b,4a] and
cyclooxygenase-2 inhibitory activities [4b]. We previously reported
that acetophenones from this plant exhibit cytotoxic activity against
KB and HCT-8 cells [4c,d]. We here report the isolation and
structural elucidation of three new acetophenones from the stems of
A. pedunculata collected in Taiwan, and the anti-proliferative
activity of 11 acetophenones isolated from this plant towards human
leukemia cell lines.
An EtOAc extract of stems of A. pedunculata was fractionated by
silica gel column chromatography and preparative TLC to obtain
eight known and three new acetophenones, named acrophenone A
(1), B (2), and C (3) (Figure 1).
Acrophenone A (1) was obtained as a colorless oil. Its molecular
formula was determined to be C
19
H
24
O
5
by HREIMS. UV bands
were observed at
max
228, 262, and 286 nm. The IR spectrum
showed absorption bands due to a hydroxy group and a conjugated
carbonyl group at
max
3444 and 1693 cm
-1
, respectively. The
1
H
NMR (CDCl
3
) spectrum revealed a singlet methoxy group ( 3.68)
and a singlet acetyl group ( 2.42). The appearance of a pair of
doublets at 5.44, 6.41 (each 1H, J = 9.8 Hz), together with
two 3H-singlets at 1.34 and 1.35, indicated the presence of a 2,2-
dimethylpyran ring system in the molecule. Furthermore, two 3H-
singlets at 1.26 and 1.27, methylene proton signals at 2.55 and
2.80 (each 1H, dd, J = 17.0, 5.2 Hz), and a methine proton signal at
3.70 (1H, br s) were observed. These signals, coupled with the
13
C
NMR signals at 25.9 (t), 69.0 (d), 77.8 (s), 24.7 (q) and 21.7 (q),
suggested the presence of the CH
2
-CH(OH)-C(CH
3
)
2
group. In
the HMBC experiment (Table 1), the C-H long-range correlations
from H-1” to C-6, and from H-2” to C-7, indicated placement of the
Figure 1: Structures of the acetophenones isolated from Acronychia pedunculata.
2,2-dimethylpyran ring at C-6/C-7. The C-H long-range correlation
from H-1’ to C-4 and C-5 indicated placement of the 2,2-dimethyl-
3-hydroxydihydropyran ring at C-4/C-5. In the NOE experiments,
irradiation of the methyl proton at 2.42 (H-2) resulted in 2% area
increases of both 8-OCH
3
(3.68) and H-4’ ( 1.26). Irradiation of
the methoxy proton at 8-OCH
3
(3.68) resulted in a 6% area
increase of H-1” ( 6.41). On the basis of these results, the structure
of acrophenone A was proposed to be that of 1.
To confirm this structure, we synthesized acrophenone A (1) from a
commercially available 2,4,6-trihydroxyacetophenone monohydrate
(8) (Figure 2). Treatment of the monomethylate (9) obtained from 8
with 3-chloro-3-methyl-1-butyne in THF in the presence of DBU
gave 10. Catalytic hydrogenation of an EtOAc solution of 10
on Lindlar catalyst gave 11. A mixture of 11 and N,N-diethylaniline
NPC Natural Product Communications
2016
Vol. 11
No. 1
83 - 86
84 Natural Product Communications Vol. 11 (1) 2016 Ito et al.
Table 1: NMR data for acrophenone A (1), B (2), and C (3) in CDCl3.
Values in (H and C) ppm. All signals correspond to one proton, unless otherwise stated. Figures in parentheses are coupling constants (J) in Hz.
Figure 2: Synthesis of acrophenone A (1’). Reaction conditions: 1) CH3I, K2CO3, acetone, △ ; 2) 3-
chloro-3-methyl-1-butyne, DBU, THF ; 3) H2, Lindlar catalyst, EtOAc ; 4) N,N-diethylaniline, △ ; 5)
mCPBA, TsOH, CH2Cl2.
heated under reflux under argon for 2 h gave preremirol (12) in 76%
yield. This product was considered to have been formed by Claisen
rearrangement of the prenyl moiety on 11 to give an ortho-phenolic
hydroxyl group. Location of the prenyl moiety at C-5 on 12 was
indicated by observation of a NOE between a methoxy proton at
3.84 (8-OCH3) and 5.90 (H-7). Further treatment of 12 with
3-chloro-3-methyl-1-butyne in THF in the presence of DBU gave
13. Treatment of 13 with mCPBA under acidic conditions in
CH2Cl2 gave 14 in 60% yield. Cyclization of 14 under reflux in
diethylaniline afforded a colorless oil (1’) in 95% yield, and this
was determined to be identical to natural acrophenone A (1) by
spectrometric comparisons (1H NMR and MS) and co-TLC. Next,
we examined the optical purity of acrophenone A (1), []D
25 -3.4
(MeOH), using a Chiralpak AD-H HPLC column. From the results
of this analysis, acrophenone A (1) was found to occur as a partial
racemate in the ratio 5:6. The absolute configuration of the major
enantiomer of 1 remained undetermined because of the small
amount of acrophenone A (1) isolated from the natural source. On
the basis of these data, the structure of acrophenone A was
determined as shown by formula 1 in Figure 1.
Acrophenone B (2) was isolated as a colorless oil. The molecular
formula, C16H18O5, was established by HREIMS. The IR spectrum
showed absorption bands due to hydroxy and conjugated carbonyl
groups. The 1H NMR spectral data of 2 (Table 1) were similar to
those of 1, except for the presence of the characteristic signals of a
furan ring at 6.79 and 7.43 (each 1H, d, J = 2.1 Hz) instead of the
signals of the 2,2-dimethylpyran ring of 1. In the HMBC
experiment (Table 1), the C-H long-range correlations from H-2” to
C-6 and C-7 indicated the placement of the furan ring at C-6/C-7.
The C-H long-range correlation from H-1’ to C-4 and C-5 indicated
the placement of the 2,2-dimethyl-3-hydroxydihydropyran ring at
C-4/C-5. This placement is supported by observation of NOEs
between a methoxy proton at 3.96 and an aromatic doublet proton
at
6.79 (H-1”) on the furan ring and between a methyl proton at
2.45 and a methoxy proton at 3.96. These results indicated that
the structure of acrophenone B was 2. On the basis of the above
results, the structure of acrophenone B was established as 2, except
for the absolute stereochemistry.
Acrophenone C (3) was isolated as a colorless oil, C19H26O5. The IR
spectrum showed absorption bands due to hydroxy and conjugated
carbonyl groups. The 1H NMR spectral data of 3 (Table 1) were
similar to those of 1, except for the presence of the characteristic
signals of a prenyl moiety at 3.35 (2H, d, J = 7.0 Hz), 5.21 (1H,
m), 1.84, 1.78 (each 3H, s) and a D2O-exchangeable proton signal
at 5.76 instead of the signals of the 2,2-dimethylpyran ring of 1. In
the HMBC experiment (Table 1), the C-H long-range correlations
from H-1” to C-6 and C-7 indicated the placement of the prenyl
moiety at C-7. This placement is supported by observation of NOEs
between a methoxy proton at 3.70 and a doublet proton at
3.35
(H-1”) on the prenyl moiety and between a methyl proton at 2.49
and a methoxy proton at
3.70. These results indicated that the
structure of acrophenone C was 3.
Eight known compounds were also isolated and identified by
comparison of their physical data with those published. These
compounds were acronyculatin D (4) [3a], isofuranoselwynone
[5a], acronylin [3b], phenylethanone [5b], acronyculatin E [3a, 4a],
acrovestone (5) [3a, 4c, 4d], acropyrone (6) [3b], and acrovestenol
(7) [3b, 4b] (Figure 1).
The cytotoxic effects of the isolated compounds were investigated
by MTS assay using Jurkat, NALM6, K562, HPB-ALL and human
peripheral blood mononuclear cells (PBMNCs). Of the investigated
Acetophenone from Acronychia pedunculata and their antiproliferative effects Natural Product Communications Vol. 11 (1) 2016 85
compounds, acrovestone (5), acropyrone (6) and acrovestenol (7),
which are dimer compounds, strikingly inhibited the proliferation of
all leukemia cell lines tested (Table 2), but not the proliferation of
PBMNCs. In contrast, acronyculatin-D (4), a monomeric
acetophenone, only modestly inhibited the proliferation of NALM6
and K562 cells (IC50: 46.5 1.5 and 41.9 3.6 M). The IC50 of
acrovestenol (7) was about 2-fold higher than that of monomeric
compounds such as acronyculatin-D (4) and acronylin, consistent
with a previous report [3b].
Table 2: IC50 values of acetophenone derivatives against four human tumor cell lines
and a normal cell line.
IC50 Values represent the mean±SD (n=3). Epigallocathechin gallate (EGCG); negative
control, Staurospotine; positive control.
Experimental
General: Optical rotations, DIP-370 (JASCO); UV, UVIDEC-610C
double-beam spectrophotometer (JASCO); IR, IR-230 (JASCO);
NMR, JNM A-600 and/or ECP-500 (JEOL) NMR spectrometers;
EIMS, JMS-700 (JEOL) spectrometer with a direct inlet system.
Preparative TLC, Kieselgel 60 F254 (Merck).
Plant materials: Acronychia pedunculata (L.) Miq. (Rutaceae) was
collected in Taipei Hsien, Taiwan, in April 1986. The plant was
identified by Professor C. S. Kouh, National Cheng-Kung
University, Taiwan, and a specimen has been deposited in the
herbarium of Cheng-Kung University.
Extraction and isolation: The dried stems (1.2 kg) of A.
pedunculata were extracted under reflux with EtOAc. The solvent
was evaporated under reduced pressure to give the EtOAc extract
(69.6 g), part of which (15.3 g) was subjected to silica gel column
chromatography (CC) eluted successively with n-hexane-acetone
(10:1, 5:1, 3:1, 1:1), acetone, and MeOH, to give 6 fractions. For
each fraction, normal phase CC on silica gel and preparative TLC
using appropriate combinations of solvents (n-hexane, EtOAc,
CHCl3, CH2Cl2, Et2O, acetone, iPr2O, benzene, and MeOH) resulted
in isolation of the following compounds. From fraction 1 (n-hexane-
acetone 10:1): acronyculatin E (46 mg), acropyrone (6, 158.0 mg),
from fraction 2 (n-hexane-acetone 5:1): phenyletanone (39.6 mg),
acrovestone (5, 65 mg), acrovestenol (7, 5.5 mg), from fraction 3
(n-hexane-acetone 3:1): acronylin (22.7 mg), acronyculatin D (4,
4.7 mg), isofuranoselwynone (2.0 mg), acrophenone A (1, 2.0 mg),
and from fraction 4 (n-hexane-acetone 1:1): acrophenone B (2, 1.8
mg) and acrophenone C (3, 2.1 mg).
Acrophenone A (1)
Colorless oil.
[]25D: -3.4 (c 0.068, MeOH).
IR max (CHCl3) cm-1: 3444, 1693.
UV max (MeOH) nm: 228, 262, 286.
1H, 13C NMR and HMBC: Table 1.
Differential NOE: irradiation at H 3.68 (8-OCH3) gave 6%
enhancement at H 6.41 (H-1”). Irradiation at H 2.42 (H-2) gave
2% enhancement at H 3.68 (8-OCH3) and 2% enhancement at H
1.26 (H-4’).
EI-MS m/z: 332 (M+, 28%), 317 (100%), 299 (16%), 245 (35%).
HR-EI-MS m/z: 332.1607 (Calcd for C19H24O5: 332.1624).
HPLC Chiralcel AD-H (250 x 4.6 mm), n-hexane/2-propanol (3:1),
flow rate 1.00 mL/min, UV detection 254 nm. Minor isomer of 1: tR
= 0.52 min, major isomer of 1: tR = 0.64 min, ratio 5:6
Acrophenone B (2)
Colorless oil.
[]25D: +2.2 (c 0.113, MeOH).
IR max (CHCl3) cm-1: 3446, 1698.
UV max (MeOH) nm: 214, 240, 288.
1H, 13C NMR and HMBC: Table 1.
Differential NOE: irradiation at H 3.96 (8-OCH3) gave 6%
enhancement at H 6.79 (H-1”). Irradiation at H 2.45 (H-2) gave
1% enhancement at H 3.96 (8-OCH3), 1% enhancement at H 1.31
(H-5’), and 1% enhancement at H 1.28 (H-4’).
EI-MS m/z: 290 (M+, 44%), 219 (100%), 203 (57%), 201 (40%).
HR-EI-MS m/z: 290.1149 (Calcd for C16H18O5: 290.1154).
HPLC Chiralcel AD-H (250 x 4.6 mm), n-hexane/2-propanol (3:1),
flow rate 1.00 mL/min, UV detection 254 nm. Minor isomer of 2: tR
= 0.66 min, major isomer of 2: tR = 0.52 min, ratio 5:2
Acrophenone C (3)
Colorless oil.
[]25D: 0 (c 0.097, MeOH).
IR max (CHCl3) cm-1: 3382, 1684.
UV max (MeOH) nm: 226, 282.
1H, 13C NMR and HMBC: Table 1.
Differential NOE: irradiation at H 3.70 (8-OCH3) gave 1%
enhancement at H 5.21 (H-2”) and 3% enhancement at H 3.35 (H-
1”). Irradiation at H 2.49 (H-2) gave 1% enhancement at H 3.70
(8-OCH3), 1% enhancement at H 1.33 (H-5’), and 1% enhancement
at H 1.31 (H-4’).
EI-MS m/z: 334 (M+, 100%), 319 (29%), 279 (25%), 263 (37%),
247 (52%), 207 (92%).
HR-EI-MS m/z: 334.1778 (Calcd for C19H26O5: 334.1780).
HPLC Chiralcel AD-H (250 x 4.6 mm), n-hexane/2-propanol (3:1),
flow rate 1.00 mL/min, UV detection 254 nm. Two isomers of 3: tR
= 0.52 min, tR = 0.60 min, ratio 1:1
2,4-Dihydroxy-6-methoxyacetophenone (9): A mixture of 2,4,6-
trihydroxyacetophenone monohydrate (8, 2.0 g), anhydrous K2CO3
(1.6 g) and methyl iodide (1.5 g) in acetone (20 mL) was refluxed
for 3 h. K2CO3 was filtered off and the filtrate was subjected to
silica gel CC with CHCl3:acetone (30:1) to give colorless oil (9, 258
mg) (13%).
1H NMR (500 MHz, acetone-d6) : 13.90 (1H, s), 6.02 (1H, d, J =
2.3 Hz), 5.93 (1H, d, J = 2.3 Hz), 3.89 (3H, s), 2.53 (3H, s); EI-MS
m/z: 182 (M+).
1,1-Dimethylpropargylether (10): A mixture of 2,4-dihydroxy-6-
methoxyacetophenone (9, 45.4 mg) and 3-chloro-3-methyl-1-butyne
(36.5 mg) in THF (0.5 mL) was stirred in the presence of DBU
(40.8 mg) for 12 h at room temperature. Diluted HCl was added to
the reaction mixture and the solution was extracted with EtOAc.
The extract was dried over anhydrous MgSO4, and the solvent was
removed by evaporation. The residue was subjected to preparative
TLC (n-hexane:acetone = 2:1) to give a colorless oil (10, 44.1 mg)
(71%).
1H NMR (500 MHz, CDCl3) : 13.84 (1H, s), 6.57 (1H, d, J = 2.3
Hz), 6.12 (1H, d, J = 2.3 Hz), 3.85 (3H, s), 2.67 (1H, s), 2.61 (3H,
s), 1.72 (6H, s).
EI-MS m/z: 248 (M+).
1,1-Dimethylallylether (11): In the presence of a catalytic amount
of Lindlar’s catalyst, an EtOAc solution (1.0 mL) of 1,1-
86 Natural Product Communications Vol. 11 (1) 2016 Ito et al.
dimethylpropargylether (10, 26.5 mg) was stirred under hydrogen
for 12 h at room temperature. The solution was filtered and the
filtrate was concentrated under reduced pressure. The residue was
subjected to silica gel preparative TLC (n-hexane:acetone = 2:1) to
yield 1,1-dimethylallylether (11, 19.4 mg) (73%).
1H NMR (500 MHz, CDCl3) : 13.84 (1H, s), 6.19 (1H, d, J = 2.3
Hz), 6.12 (1H, dd, J = 17.6, 10.9 Hz), 5.96 (1H, d, J = 2.3 Hz), 5.24
(1H, d, J = 17.6 Hz), 5.21 (1H, d, J = 10.9 Hz), 3.82 (3H, s), 2.59
(3H, s), 1.54 (6H, s); EI-MS m/z: 250 (M+).
Preremirol (12): A mixture of 1,1-dimethylallylether (11, 18.5 mg)
in N,N-diethylaniline (0.5 mL) was refluxed under argon for 2 h.
Diluted HCl was added to the reaction mixture and the solution was
extracted with diethyl ether. The extract was dried over anhydrous
MgSO4, and the solvent was removed by evaporation. The residue
was subjected to preparative TLC (diisopropyl ether:acetone = 30:1)
to give a colorless oil (12, 14.1 mg) (76%).
1H NMR (500 MHz, CDCl3) : 14.38 (1H, s), 6.13 (1H, s, br), 5.90
(1H, s), 5.26 (1H, m), 3.84 (3H, s), 3.37 (2H, d, J = 7.3 Hz), 2.61
(3H, s), 1.82 (3H, s), 1.77 (3H, s).
EI-MS m/z: 250 (M+).
Preremirol 1,1-dimethylpropargylether (13): A mixture of
preremirol (12, 20.9 mg) and 3-chloro-3-methyl-1-butyne (18.3 mg)
in THF (0.5 mL) was stirred in the presence of DBU (20.4 mg) for
12 h at room temperature. Diluted HCl was added to the reaction
mixture and the solution was extracted with EtOAc. The extract was
dried over anhydrous MgSO4, and the solvent was removed
by evaporation. The residue was subjected to preparative TLC
(n-hexane:acetone = 2:1) to give a colorless oil (13, 11.1 mg) (42%).
1H NMR (500 MHz, CDCl3) : 13.85 (1H, s), 6.79 (1H, s), 5.11
(1H, m), 3.78 (3H, s), 3.17 (2H, d, J = 7.3 Hz), 2.61 (1H, s), 2.54
(3H, s), 1.68 (3H, s), 1.65 (6H, s), 1.59 (3H, s).
EI-MS m/z: 316 (M+).
Cyclization reaction of 13: A mixture of 13 (13.8 mg) and m-CPBA
(8.6 mg) in CH2Cl2 (0.3 mL) was stirred in the presence of
p-toluenesulfonic acid (9.0 mg) for 24 h at room temperature.
Sodium thiosulfate solution was added to the reaction mixture and
the solution was extracted with CH2Cl2. The extract was washed
with saturated aqueous Na2CO3 solution, dried with anhydrous
MgSO4, and the solvent was evaporated. The residue was subjected
to preparative TLC (n-hexane:acetone = 2:1) to give a colorless oil
(14, 8.7 mg) (60%).
1H NMR (500 MHz, CDCl3) : 6.86 (1H, s), 3.76 (3H, s), 3.76 (1H,
overlapped with OCH3), 2.85 (1H, dd, J = 17.1, 5.4 Hz), 2.63 (1H,
s), 2.61 (1H, dd, J = 17.1, 5.4 Hz), 2.47 (3H, s), 1.84 (1H, s, br),
1.70 (3H, s), 1.69 (3H, s), 1.31 (3H, s), 1.30 (3H, s).
EI-MS m/z: 332 (M+).
Thermal ring closure of 14: A mixture of 14 (6.4 mg) in N,N-
diethylaniline (0.5 mL) was refluxed under argon for 2 h. Diluted
HCl was added to the reaction mixture and the solution was
extracted with diethyl ether. The extract was dried over anhydrous
MgSO4, and the solvent was evaporated. The residue was subjected
to preparative TLC (n-hexane:acetone = 2:1) to give a colorless oil
(1’, 6.1 mg) (95%), and was found to be identical with natural
acrophenone A (1) by spectrometric comparisons (1H NMR and
MS) and co-TLC.
Cell lines and culture: Human acute T cell leukemia (Jurkat), B
cell precursor leukemia (NALM6), erythroid leukemia (K562) and
T cell leukemia (HPB-ALL) cells obtained from Tohoku University
were grown in RPMI 1640 supplemented with 10% heat-inactivated
FCS, penicillin at 100 units/mL, streptomycin at 100 g/mL,
non-essential amino acids, sodium pyruvate and HEPES under 5%
CO2 at 37C.
Isolated peripheral blood mononuclear cells and culture: Blood
samples from healthy volunteers were collected and heparin was
added to prevent coagulation. The samples were diluted at a 1:1
ratio with PBS, layered onto Histopaque®-1077 at a volume ratio of
1:1, and centrifuged at 400 x g for 30 min. The PBMNC layer was
collected and washed twice with culture medium, and then the cells
were suspended in fresh medium. The PBMNCs were seeded onto
96-well plates at a density of 1105 cells/well and assayed in cell
viability assays.
Cell viability assays: Each cell type was seeded onto 96-well plates
at a density of 5104 cells/well. After overnight incubation, the cells
were treated for 24 h with either the isolated compounds or DMSO
as the vehicle control. MTS Reagent (CellTiter 96 AQueousOne
Solution Cell Proliferation Assay; Promega) was added to each well
according to the manufacturer’s instructions. Absorbance was
monitored at 490 nm using a microplate reader (Molecular Devices,
Sunnyvale, CA, USA). Cell viability (%) was normalized to the
vehicle control. Each experiment was performed in triplicate.
(-)-epigallocathechin gallate (EGCG) and staurosporine were used
as the negative and positive controls, respectively. IC50 values were
calculated using Softmax Pro6 (Molecular Devices).
Statistical analysis: Statistical analysis was performed by one-way
analysis of variance, followed by Tukey’s test using Statistical
Package for the Social Sciences (SPSS) software (version 16.00;
SPSS Inc., Chicago, IL, USA). Results are expressed as mean ± SD.
Acknowledgments - This work was supported by JSPS KAKENHI
Grant Number 23590026.
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Natural Product Communications Vol. 11 (1) 2016
Published online (www.naturalproduct.us)
Acetophenones Isolated from Acronychia pedunculata and their Anti-proliferative Activities
Chihiro Ito, Takuya Matsui, Yoshiaki Ban, Tian-Shung Wu and Masataka Itoigawa 83
Xanthones from Garcinia propinqua Roots
Pornphimol Meesakul, Acharavadee Pansanit, Wisanu Maneerat, Tawanun Sripisut, Thunwadee Ritthiwigrom, Theeraphan Machan,
Sarot Cheenpracha and Surat Laphookhieo 87
A New Antibacterial Tetrahydronaphthalene Lignanamide, Foveolatamide, from the Stems of Ficus foveolata
Wirod Meerungrueang and Parkphoom Panichayupakaranant 91
Antifungal and Cytotoxic Assessment of Lapachol Derivatives Produced by Fungal Biotransformation
Eliane O. Silva, Antonio Ruano-González, Raquel A. dos Santos, Rosario Sánchez-Maestre, Niege A. J. C. Furtado,
Isidro G. Collado and Josefina Aleu 95
Polyphenols and Volatile Compounds in Commercial Chokeberry (Aronia melanocarpa) Products
Annalisa Romani, Pamela Vignolini, Francesca Ieri and Daniela Heimler 99
Volatile Components of the Stressed Liverwort Conocephalum conicum
Nurunajah Ab Ghani, Agnieszka Ludwiczuk, Nor Hadiani Ismail and Yoshinori Asakawa 103
Chemical Composition of the Essential Oil of Bupleurum fontanesii (Apiaceae) Growing Wild in Sicily and its Activity on
Microorganisms Affecting Historical Art Crafts
Simona Casiglia, Maurizio Bruno, Federica Senatore and Felice Senatore 105
Chemical Composition and Antimicrobial Activity of the Essential Oil from Aerial Parts of Algerian Pulicaria mauritanica
Mohammed Gherib, Chahrazed Bekhechi, Fewzia Atik Bekkara, Ange Bighelli, Joseph Casanova and Félix Tomi 109
Origanum vulgare and Thymbra capitata Essential Oils from Spain: Determination of Aromatic Profile and Bioactivities
Alejandro Carrasco, Enrique Perez, Ana-Belen Cutillas, Ramiro Martinez-Gutierrez, Virginia Tomas and Jose Tudela 113
Accounts/Reviews
In vivo Cytotoxicity Studies of Amaryllidaceae Alkaloids
Jerald J. Nair, Jaume Bastida and Johannes van Staden 121
Natural Product Communications
2016
Volume 11, Number 1
Contents
Original Paper
Chemical Constituents and LC-profile of Fresh Formosan Lonicera japonica Flower Buds
I-Wen Lo, Yuan-Bin Cheng, Yi-Jin Hsieh, Tsong-Long Hwang, Deng-En Shieh, Fang-Rong Chang and Yang-Chang Wu 1
Isolation and Characterization of Sclerienone C from Scleria striatinux
Kennedy D. Nyongbela, Felix L. Makolo, Thomas R. Hoye and Simon MN Efange 5
Cytotoxic and Pro-apoptotic Activities of Sesquiterpene Lactones from Inula britannica
Ping Xiang, Xin Guo, Yang-Yang Han, Jin-Ming Gao and Jiang-Jiang Tang 7
Influence of Merosesquiterpenoids from Marine Sponges on Seedling Root Growth of Agricultural Plants
Elena L. Chaikina, Natalia K. Utkina and Mikhail M. Anisimov 11
A New Cytotoxic Clerodane Diterpene from Casearia graveolens Twigs
Pornphimol Meesakul, Thunwadee Ritthiwigrom, Sarot Cheenpracha, Tawanun Sripisut, Wisanu Maneerat, Theeraphan Machan and
Surat Laphookhieo 13
Influence of Tanshinone IIA on the Apoptosis of Human Esophageal Ec-109 Cells
Yan-qin Zhu, Bai-Yan Wang, Fang Wu, Yong-kang An and Xin-qiang Zhou 17
Trocheliolide B, a New Cembranoidal Diterpene from the Octocoral Sarcophyton trocheliophorum
Kuan-Ming Liu, Yu-Hsuan Lan, Ching-Chyuan Su and Ping-Jyun Sung 21
Synthesis of a Novel 1,2,4-Oxadiazole Diterpene from the Oxime of the Methyl Ester of 1β,13-Epoxydihydroquinopimaric Acid
Elena V. Tretyakova, Elena V. Salimova, Viсtor N. Odinokov and Usein M. Dzhemilev 23
Phytochemical and Biological Investigations of Conradina canescens
Noura S. Dosoky, Debra M. Moriarity and William N. Setzer 25
A New Taraxastane-type Triterpenoid from Cleistocalyx operculatus
Phan Minh Giang, Vu Thi Thu Phuong and Truong Thi To Chinh 29
Anti-allergic Inflammatory Triterpenoids Isolated from the Spikes of Prunella vulgaris
Hyun Gyu Choi, Tae Hoon Kim, Sang-Hyun Kim and Jeong Ah Kim 31
Inhibition of Alpha-Glucosidase by Synthetic Derivatives of Lupane, Oleanane, Ursane and Dammarane Triterpenoids
El'mira F. Khusnutdinova, Irina E. Smirnova, Gul'nara V. Giniyatullina, Natal'ya I. Medvedeva, Emil Yu. Yamansarov,
Dmitri V. Kazakov, Oxana B. Kazakova, Pham T. Linh, Do Quoc Viet and DoThi Thu Huong 33
Cycloartane-Type Saponins from Astragalus tmoleus var. tmoleus
Sibel Avunduk, Anne-Claire Mitaine-Offer, Tomofumi Miyamoto, Chiaki Tanaka and Marie-Aleth Lacaille-Dubois 37
Profiling and Metabolism of Sterols in the Weaver Ant Genus Oecophylla
Nanna H. Vidkjær, Karl-Martin V. Jensen, René Gislum and Inge S. Fomsgaard 39
Steroidal Glucosides from the Rhizomes of Tacca chantrieri and Their Inhibitory Activities of NO Production in BV2 Cells
Pham Hai Yen, Vu Thi Quynh Chi, Dong-Cheol Kim, Wonmin Ko, Hyuncheol Oh, Youn-Chul Kim, Duong Thi Dung,
Nguyen Thi Viet Thanh, Tran Hong Quang, Nguyen Thi Thanh Ngan, Nguyen Xuan Nhiem, Hoang Le Tuan Anh,
Chau Van Minh and Phan Van Kiem 45
Antimicrobial Metabolites from a Marine-Derived Actinomycete in Vietnam’s East Sea
Quyen Vu Thi, Van Hieu Tran, Huong Doan Thi Mai, Cong Vinh Le, Minh Le Thi Hong, Brian T. Murphy,
Van Minh Chau and Van Cuong Pham 49
Aspidosperma-type Alkaloids from Melodinus suaveolens
Jian Zhang, Min Song, Zhi-wen Liu, Hua Xiao, Chun-lin Fan, Xiao-qi Zhang and Wen-cai Ye 53
Molecular Docking and Binding Mode Analysis of Plant Alkaloids as in vitro and in silico Inhibitors of Trypanothione
Reductase from Trypanosoma cruzi
Alonso J. Argüelles, Geoffrey A. Cordell and Helena Maruenda 57
Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways
Di Wang, Yongfeng Zhang, Jiahui Lu, Yang Wang, Junyue Wang, Qingfan Meng, Robert J. Lee, Di Wang and Lesheng Teng 63
Absolute Stereochemistry of the -Hydroxy Acid Unit in Hantupeptins and Trungapeptins
Deepak Kumar Gupta, Gary Chi Ying Ding, Yong Chua Teo and Lik Tong Tan 69
Electron Ionization Mass Spectrometry-based Metabolomics Studies of Sophora flavescens can Identify the
Geographical Origin of Root Samples
Ryuichiro Suzuki, Hisahiro Kai, Yoshihiro Uesawa, Koji Matsuno, Yoshihito Okada and Yoshiaki Shirataki 73
Qualitative and Quantitative Analysis of Flower Pigments in Chocolate Cosmos, Cosmos atrosanguineus, and its Hybrids
Kotarou Amamiya and Tsukasa Iwashina 77
A New Geranylated Chalcone from Andrographis lobelioides
Manne Sumalatha, Aluru Rammohan, Duvvuru Gunasekar, Alexandre Deville and Bernard Bodo 79
Pterocarpans from Derris laxiflora
Shih-Chang Chien, Hsi-Lin Chiu, Wei-Yi Cheng, Yong-Han Hong, Sheng-Yang Wang, Jyh-Horng Wu, Chun-Ching Shih,
Jung-Chun Liao and Yueh-Hsiung Kuo 81
Continued inside backcover
