Two novel non-holostane type glycosides from the viscera of sea cucumber Apostichopus japonicus

Article abstract of DOI:10.1080/10286020.2019.1576643

Two novel glycosides, apostichoposide A₁ (1) and B₁ (2), were isolated from the viscera of Chinese sea cucumbers (Apostichopus japonicus, Selenka) collected in the Bohai sea. Both the isolated glycosides were characterized by non-holostane type aglycones having 18(16)-lactone and 7(8)-double bond. Cytotoxic activities of the two compounds were evaluated against three human cancer cell lines. Compound 1 had adequate cytotoxic activity against MGC-803 and PC-3M cell lines. Our results indicated that glycosides present in A. japonicus viscera are an important high value resource for biotechnological applications.

Full text of DOI:10.1080/10286020.2019.1576643

Journal of Asian Natural Products Research
ISSN: 1028-6020 (Print) 1477-2213 (Online) Journal homepage: https://www.tandfonline.com/loi/ganp20
Two novel non-holostane type glycosides from the
viscera of sea cucumber Apostichopus japonicus
Xuan-Ming Zhang, Li-Wen Han, Wen-Long Sheng, Xiao-Bin Li, Shan-Shan
Zhang, Jing-Lan Guo, Hou-Wen Lin & Ke-Chun Liu
To cite this article: Xuan-Ming Zhang, Li-Wen Han, Wen-Long Sheng, Xiao-Bin Li, Shan-
Shan Zhang, Jing-Lan Guo, Hou-Wen Lin & Ke-Chun Liu (2019): Two novel non-holostane type
glycosides from the viscera of sea cucumber Apostichopusꢀjaponicus, Journal of Asian Natural
Products Research, DOI: 10.1080/10286020.2019.1576643
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
https://doi.org/10.1080/10286020.2019.1576643
Two novel non-holostane type glycosides from the
viscera of sea cucumber Apostichopus japonicus
a
a
a
a
ꢀ
ꢀ
Xuan-Ming Zhang , Li-Wen Han , Wen-Long Sheng , Xiao-Bin Li , Shan-Shan
Zhanga, Jing-Lan Guoa, Hou-Wen Linb and Ke-Chun Liua
aKey Laboratory for Drug Screening Technology & Key Laboratory for Biosensors, Biology Institute,
b
Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China; Research
Center for Marine Drugs, State Key Laboratory of Oncogenes and Related Genes, Department of
Pharmacy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai
200127, China
ABSTRACT
ARTICLE HISTORY
Received 25 November 2018
Accepted 28 January 2019
Two novel glycosides, apostichoposide A1 (1) and B1 (2), were iso-
lated from the viscera of Chinese sea cucumbers (Apostichopus
japonicus, Selenka) collected in the Bohai sea. Both the isolated
glycosides were characterized by non-holostane type aglycones
having 18(16)-lactone and 7(8)-double bond. Cytotoxic activities
of the two compounds were evaluated against three human can-
cer cell lines. Compound 1 had adequate cytotoxic activity against
MGC-803 and PC-3M cell lines. Our results indicated that glyco-
sides present in A. japonicus viscera are an important high value
resource for biotechnological applications.
KEYWORDS
Apostichopus japonicus;
viscera; non-holostane;
glycosides; structural
identification; antitumor
CONTACT Ke-Chun Liu
liukechun2000@163.com
Key Laboratory for Drug Screening Technology & Key
Laboratory for Biosensors, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan
250103, China
ꢀ
The authors contributed equally to this work.
Supplemental data for this article can be accessed here.
ß 2019 Informa UK Limited, trading as Taylor & Francis Group

2
X.-M. ZHANG ET AL.
1. Introduction
Sea cucumbers (class Holothurioidea) are soft-bodied, wormlike echinoderms.
Triterpene glycosides are characteristic metabolites of sea cucumbers and they appear
to be particularly concentrated in viscera. These marine natural products have com-
plicated structures, with the majority being the holostane type; however, there are
also rare non-holostane types [1–4]. The monosaccharide units in the carbohydrate
chain are mainly composed of D-xylose, D-glucose, D-quinovose and 3-O-methyl-D-
glucose. The glycosides exhibit a wide spectrum of therapeutic applications due to
their anti-cancer, cardiovascular, anti-diabetic, anti-inflammatory, cholesterol-lower-
ing, anti-angiogenesis, and anti-oxidant activities [5–11].
In the present study, we describe the isolation of two novel triterpene glycosides
from the viscera of the Chinese sea cucumber A. japonicus. Their structures were elu-
cidated on the basis of NMR analyses and mass spectrometry. All compounds were
evaluated for their cytotoxicity against MGC-803, PC-3M and MCF-7 cell lines. Our
findings will assist in furthering our understanding of the industrial applications of
sea cucumber viscera.
2. Results and discussion
Compound 1 (Figure 1), a white amorphous powder, exhibited a quasimolecular ion
peak at m/z 1085.5522 ([M – H–O]ꢁ, calcd 1085.5532, an unusual fragmentation
caused by 18(16)-lactone ring [12]) on the basis of HR-ESI-MS, and its molecular for-
mula was determined to be C54H86O23. The 1H NMR spectrum of compound 1
revealed six singlet methyl groups (dH 1.07, 1.16, 1.35, 1.42, 1.48, 1.72) and a second-
ary methyl group at dH 1.76 (3H, d, J ¼ 5.9 Hz). The 13C NMR spectrum displayed 54
carbon signals, and seven signals at dC 17.9, 18.8, 22.7, 24.7, 27.8, 29.3 and 35.1 were
assigned to methyl groups. An olefinic proton dH 5.66 (1H, m) with corresponding
Figure 1. Chemical structures of the glycosides 1 and 2 isolated from Apostichopus japonicus.

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
3
1
Figure 2. 1H, H-COSY (—) and key HMBC (!) correlations for the glycosides 1 and 2.
carbon signals at dC 123.1 (C-7) and 148.5 (C-8) demonstrated the presence of the
7(8) double bond, and the signals of the olefinic protons at dH 4.80 and 4.83 (2H,
each brs) with corresponding carbon signals at dC 146.5 (C-25) and 111.0 (C-26)
indicated the presence of terminal 25(26) double bond. The aglycone part of com-
pound 1 confirmed the presence of an 18(16)-lactone that was deduced from the sig-
nals of quaternary carbons at dC 182.4 (C-18, a carboxy group) and dC 71.8 (C-20, an
oxygenated tertiary asymmetric carbon), the signals of an oxygen bearing methine at
dC 80.2 (C-16) and dH 5.05 (1H, brs, H-16), as well as the correlation H-16/C-18 in
the HMBC spectrum (Figure 2). (S)-configuration of C-16 asymmetric center was
confirmed by the absence of coupling constant J17/16 for H-17 signal (dH 2.62, s) in
the 1H NMR spectrum and the correlation H-16/H-21 in the ROESY spectrum.
Additionally, the ROESY correlations of H-5/H-3, Me-31; H-9/Me-19; H-16, H-17/
Me-21; H-17/Me-32 confirmed the common (3S, 5R, 9S, 10R, 13S, 14S, 16S, 17R,
20S)-configurations in lanostane-type aglycone (Figure 3), and the structure of com-
pound 1 is characteristic of the non-holostane type skeleton [13]. The presence of
four anomeric proton signals at dH 4.81 (1H, d, J ¼ 7.0 Hz, Glc H-1’), 5.00 (1H, d,
J ¼ 7.8 Hz, Qui H-1’’), 5.18 (1H, d, J ¼ 7.5 Hz, Glc H-1’’’), and 5.29 (1H, d, J ¼ 8.0 Hz,
Glc H-1’’’’) correlated by the HSQC spectrum with the signals of anomeric carbons at
dC 106.1, 105.5, 106.2, and 106.2, respectively. The HMBC correlation of dH 4.81 (Glc
H-1’)/dC 89.7 (Agly C-3) corroborated that the sugars were linked to C-3 position of
the aglycone. HMBC cross-peaks of dH 5.00 (Qui H-1’’)/dC 88.0 (Glc C-2’), dH 5.18
(Glc H-1’’’)/dC 84.9 (Qui C-4’’), and dH 5.29 (Glc H-1’’’’)/dC 88.5 (Glc C-3’’’)

4
X.-M. ZHANG ET AL.
Figure 3. Key ROESY correlations for compound 1.
suggested a Glc-(1!3)-Glc-(1!4)-Qiu-(1!2)-Glc sequence. This was also confirmed
by the ROESY cross-peaks at dH 5.00 (Qui H-1’’)/dH 3.67 (Glc H-2’), dH 5.18 (Glc H-
1’’’)/dH 4.06 (Qui H-4’’), and dH 5.29 (Glc H-1’’’’)/dH 4.24 (Glc H-3’’’). The sugars
were determined by HPLC analysis to be D for glucose and D for quinovose. Based
on the previous results, the structure of compound 1 was elucidated as 3b-O-[b-D-
glucopyranosyl-(1!3)-b-D-glucopyranosyl-(1!4)-b-D-quinovopyranosyl-(1!2)-b-D-
glucopyranosyl]-9bH, 20(S)-hydroxylanosta-7,25-diene-18(16)-lactone and labeled
apostichoposide A1.
Compound 2 (Figure 1), a white amorphous powder, exhibited a quasimolecular
ion peak at m/z 1071.5319 [M – H]ꢁ in the HR-ESI-MS, and its molecular formula
was determined to be C53H84O22. Analysis of the NMR data of compound 2 revealed
the same aglycone to that of compound 1 and a sugar chain linked at the C-3
1
hydroxyl group. The H NMR spectrum of compound 2 showed four anomeric pro-
ton signals at dH 4.82 (1H, d, J ¼ 7.0 Hz, Glc H-1’), 4.97 (1H, d, J ¼ 7.8 Hz, Qui H-
1’’), 5.19 (1H, d, J ¼ 7.4 Hz, Xyl H-1’’’), and 5.32 (1H, d, J ¼ 7.8 Hz, Glc H-1’’’’), which
correlated with the corresponding anomeric carbon signals at dC 106.0, 106.2, 105.5,
and 106.3, respectively. HMBC cross-peaks (Figure 2) of dH 4.97 (Qui H-1’’)/dC 88.1
(Glc C-2’), dH 5.19 (Xyl H-1’’’)/dC 85.0 (Qui C-4’’), and dH 5.32 (Glc H-1’’’’)/dC 88.8
(Xyl C-3’’’) suggested a Glc-(1!3)-Xyl-(1!4)-Qui-(1!2)-Glc sequence of 3-O-oligo-
saccharidic moiety. Moreover, this was confirmed by the ROESY cross-peaks of dH
4.97 (Qui H-1’’)/dH 3.66 (Glc H-2’), dH 5.19 (Xyl H-1’’’)/dH 4.06 (Qui H-4’’), and dH
5.32 (Glc H-1’’’’)/dH 4.23 (Xyl H-3’’’). The sugars were determined by HPLC analysis
to be D for glucose, D for xylose and D for quinovose. Therefore, the structure of
compound 2 was deduced to be 3b-O-[b-D-glucopyranosyl-(1!3)-b-D- xylopyrano-
syl-(1!4)-b-D-quinovopyranosyl-(1!2)-b-D-glucopyranosyl]-9bH,20(S)-hydroxyla-
nosta-7,25-diene-18(16)-lactone and labeled apostichoposide B1.
The cytotoxic activities of compounds 1 and 2 against three human cancer cell
lines (gastric carcinoma MGC-803, prostate cancer PC-3M and breast cancer MCF-7)
were studied. It was demonstrated that compound 1 displayed adequate cytotoxic
activity against MGC-803 and PC-3M cell lines (IC50 57.22 3.72 and 76.71 4.79 lg/
ml, respectively), however, compound 2 did not decrease cell viability of MGC-803
and PC-3M cell lines at doses up to 100 lg/ml. Compounds 1 and 2 had weak effects
on MCF-7 cell proliferation with an inhibition rates of 24.1% and 29.9% at 100 lg/

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
5
Figure 4. Morphological changes in MGC-803 and PC-3M cells. (A) MGC-803, control (B) MGC-803,
compound 1 (C) PC-3M, control (D) PC-3M, compound 1.
ml, respectively. Treatment with compound 1 resulted in significant changes in the
morphology of MGC-803 and PC-3M cells (Figure 4).
3. Experimental
3.1. General experimental procedures
IR spectra were obtained using a Thermo Scientific Nicolet iS10 Fourier Transform
Infrared spectrometer (Thermo Fisher, Woburn, Massachusetts, USA) with KBr disks.
The 1D and 2D NMR spectra were recorded on a Bruker Avance III 400-MHz spec-
€
trometer (Bruker Co., Karlsruhe, Baden-Wurttemberg, Germany) in pyridine-d5 solu-
tions (Cambridge Isotope Laboratories, Tewksbury, MA, USA). HR-ESI-MS were
performed in an Agilent 6520 series Q-TOF mass spectrometer (Agilent
Technologies, Palo Alto, CA, USA). Sugar analysis was carried out on a Hitachi
HPLC system (Hitachi, Tokyo, Japan).
3.2. Viscera material
Apostichopus japonicus were collected from Penglai-Changdao, Shandong, China, in
May 2017. The species was identified by Professor Kechun Liu at the Biology
Institute of Qilu University of Technology (Shandong Academy of Sciences). The sep-
arated viscera were snap-frozen, transferred to the laboratory and stored at ꢁ20 ꢂC. A

6
X.-M. ZHANG ET AL.
voucher specimen (No.SWS0511AD) was deposited at the Key Laboratory for Drug
Screening Technology of the Biology Institute.
3.3. Extraction and isolation
The dried and minced viscera of A. japonicus (200 g) were extracted three times at
reflux with MeOH (500 ml ꢃ 3). After removing the solvent, the residual sample was
loaded onto a column containing pretreated D101 macroporous adsorption resin,
subsequently eluted with four BV (bed volume) of redistilled water, six BV of 30%
ethanol and six BV of 60% ethanol. The saponin-rich fraction was then eluted with
six BV of 90% ethanol, concentrated and dried. The saponin fraction (4.1 g) was sub-
jected to Sephadex LH-20 (CH2Cl2/MeOH, 1:1), yielding three fractions (Fr. 1–3).
Fraction 2 (2.2 g) was applied to silica gel CC and eluted with a continuous gradient
of CH2Cl2/MeOH (100:2–100:80, v/v), resulting in 11 fractions (Fr. 2.1–Fr. 2.11). On
the basis of RP-18 TLC analysis, Fr. 2.8 was further purified by ODS column with
ACN/H2O (20–60%, v/v) as eluent to give compound 1 (23.1 mg); Fr. 2.9 was also
chromatographed over an ODS column, which was eluted with ACN/H2O (10–60%,
v/v) to result in compound 2 (10.8 mg).
Table 1. 1H and 13C NMR spectral data of the aglycone moieties of compounds 1 and 2.a
1
2
No.
dH
1.49-1.52 (m)
dC
dH
1.49-1.51 (m)
dC
1
36.3
27.4
89.7
40.2
48.4
24.0
123.1
148.5
46.7
36.6
22.6
21.1
55.4
46.5
45.3
80.2
62.7
182.4
24.7
71.8
27.8
43.2
22.9
39.0
146.5
111.0
22.7
17.9
29.3
35.1
36.2
27.3
89.6
40.1
48.3
23.9
123.0
148.4
46.6
36.5
22.5
21.1
55.3
46.4
45.2
80.1
62.8
182.3
24.6
71.7
27.7
43.1
22.8
38.9
146.4
110.9
22.6
17.8
29.2
35.0
2
3
4
5
6
7
8
9
1.92-1.96 (m), 2.19-2.24 (m)
1.92-1.96 (m), 2.20-2.24 (m)
3.34 (dd, J¼11.8, 3.5 Hz)
3.34 (dd, J¼11.2, 3.4 Hz)
—
—
1.01-1.05 (m)
2.04-2.08 (m)
5.64-5.67 (m)
1.01-1.05 (m)
2.06-2.10 (m)
5.64-5.67 (m)
—
—
3.27 (brd, J¼13.1)
3.27 (brd, J¼13.0)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
30
31
32
—
—
1.52-1.58 (m), 1.82-1.86 (m)
2.15-2.17 (m), 2.65-2.68 (m)
1.56-1.60 (m), 1.79-1.82 (m)
2.14-2.17 (m), 2.65-2.68 (m)
—
—
—
—
1.95-1.99 (m), 2.16-2.19 (m)
5.05 (brs)
2.62 (s)
1.92-1.96 (m), 2.14-2.17 (m)
5.05 (brs)
2.61 (s)
—
—
1.07 (s)
1.07 (s)
—
—
1.48 (s)
1.48 (s)
1.78-1.81 (m)
1.80-1.82 (m), 1.98-2.02 (m)
2.07-2.09 (m)
—
4.80 (brs), 4.83 (brs)
1.72 (s)
1.16 (s)
1.35 (s)
1.42 (s)
1.76-1.80 (m)
1.78-1.81 (m), 2.03-2.07 (m)
2.06-2.08 (m)
—
4.81 (brs), 4.83 (brs)
1.72 (s)
1.16 (s)
1.35 (s)
1.42 (s)
ain pyridine-d5, 400/100 MHz.

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
7
Table 2. 1H and 13C NMR spectral data of the sugar portions of compounds 1 and 2.a
1
2
No.
dH
dC
dH
dC
Glc-1’
2’
3’
4’
5’
6’
Qui-1’’
2’’
3’’
4’’
4.81 (d, J ¼ 7.0 Hz)
3.65-3.69 (m)
4.08-4.11 (m)
4.17-4.21 (m)
3.97-4.01 (m)
4.19-4.21(m), 4.48-4.50(m)
5.00 (d, J ¼ 7.8 Hz)
4.23-4.27 (m)
3.98-4.01 (m)
4.04-4.08 (m)
4.16-4.20 (m)
1.76 (d, J ¼ 5.9 Hz)
5.18 (d, J ¼ 7.5 Hz)
4.06-4.09 (m)
4.21-4.26 (m)
4.00-4.04 (m)
106.1
88.0
76.6
71.1
78.9
62.9
105.5
76.5
75.6
84.9
71.3
18.8
106.2
75.5
88.5
70.4
78.5
61.3
106.2
78.9
76.9
72.3
78.8
63.2
4.82 (d, J ¼ 7.0 Hz)
3.64-3.68 (m)
4.12-4.15 (m)
4.01-4.04 (m)
3.92-3.96 (m)
4.17-4.21(m), 4.50-4.54(m)
4.97 (d, J ¼ 7.8 Hz)
4.23-4.27 (m)
4.06-4.09 (m)
4.04-4.08 (m)
4.17-4.21 (m)
1.76 (d, J ¼ 5.9 Hz)
5.19 (d, J ¼ 7.4 Hz)
3.81-3.84 (m)
4.21-4.25 (m)
4.02-4.06 (m)
106.0
88.1
76.5
71.7
78.4
62.9
106.2
76.0
74.2
85.0
71.2
18.6
105.5
72.1
88.8
70.4
67.2
—
5’’
6’’
Glc/Xyl-1’’’
2’’’
3’’’
4’’’
5’’’
6’’’
Glc-1’’’’
2’’’’
3’’’’
4’’’’
5’’’’
6’’’’
4.20-4.24 (m)
3.66-3.69(m), 4.31-4.34(m)
4.40-4.44(m), 4.61-4.65(m)
5.29 (d, J ¼ 8.0 Hz)
4.08-4.10 (m)
3.84-3.87 (m)
3.80-3.83 (m)
4.02-4.04 (m)
4.28-4.32(m), 4.60-4.64(m)
—
5.32 (d, J ¼ 7.8 Hz)
4.21-4.25 (m)
4.06-4.09 (m)
4.21-4.25 (m)
4.02-4.05 (m)
106.3
78.7
76.9
72.0
79.1
62.9
4.31-4.34(m), 4.51-4.54(m)
ain pyridine-d5, 400/100 MHz.
3.3.1. Apostichoposide A1 (1)
White amorphous powder; IR (KBr) ꢀmax cmꢁ1: 3299, 2924, 2856, 1748, 1377, 1065,
1
1033; H and 13C NMR spectral data see Tables 1 and 2; HR-ESI-MS m/z: 1085.5522
[M – H–O]ꢁ (calcd for C54H85O22, 1085.5532), 1121.5269 [M þ Cl–O]ꢁ (calcd for
C54H86O22Cl, 1121.5299).
3.3.2. Apostichoposide B1 (2)
White amorphous powder; IR (KBr) ꢀmax cmꢁ1: 3359, 2921, 2845, 1743, 1374, 1050;
1
1032; H and 13C NMR spectral data see Tables 1 and 2; HR-ESI-MS m/z: 1071.5319
[M ꢁ H]ꢁ (calcd for C53H83O22, 1071.5376), 1107.5105 [M þ Cl]ꢁ (calcd for
C53H84O22Cl, 1107.5143).
3.4. Acid hydrolysis of compounds 1 and 2
The configuration of sugars was determined using a previously published method
with minor modifications [14]. Compounds 1 and 2 (3 mg) were hydrolyzed in 1 M
HCl at 80 ꢂC for 4 h. The reaction mixture was neutralized with Na2CO3, filtered and
extracted with CH2Cl2. The aqueous layer was dried in vacuum to yield the sugar
portion. The obtained sugar portion was treated with L-cysteine methyl ester hydro-
chloride (4 mg) in pyridine (1 ml) and heated at 60 ꢂC for 1 h. Subsequently, o-tolyl
isothiocyanate (100 ll in 1 ml pyridine) was added and the mixture was heated for an
additional 1 h to yield the corresponding o-tolythiocarbamate derivative, which was
analyzed by HPLC and detected at 250 nm (ACN: H2O = 10:90 ꢄ 40:60, 1 ml/min,
20 min). Sugar units were identified by comparing the retention times of the

8
X.-M. ZHANG ET AL.
corresponding derivatives with those of standards: 10.61 min (D-glucose), 11.28 min
(D-xylose) and 12.08 min (D-quinovose).
3.5. Cytotoxicity assay by cell counting kit-8
The assays were conducted as described previously [15]. MGC-803, PC-3M, and
MCF-7 cells, in DEME and RPMI 1640 medium supplemented with 10% fetal bovine
serum, were seeded at 5 ꢃ 103 per well onto 96-well culture plates. Six different con-
centrations (100, 50, 25, 12.5, 6.25, and 3.125 lg/ml) of compounds 1 and 2 were
added to each well in triplicate and 5-fluorouracil was used as a positive control.
Following incubation at 37 ꢂC in 5% CO2 for 6 h, 10 ml CCK-8 solution (Dojindo,
Kyushu, Japan) was added to each well and incubated for 2 h. The morphological
changes of the cells were examined using an inverted microscope (Olympus,
Tokyo, Japan), and the absorbance of the solution was determined at 450 nm using a
microplate spectrophotometer. Cell inhibitory rate (%) = [1 - A450 (sample)/A450
(control)] ꢃ 100.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This study was financially supported by the Public Science and Technology Research Funds
Projects of Ocean (grant number 201505030), the National Natural Science Foundation of
China (grant number 81602982), and the Shandong Natural Science Foundation of China
(grant number ZR2016YL009).
References
[1] A.S. Silchenko, S.A. Avilov, A.I. Kalinovsky, P.S. Dmitrenok, V.I. Kalinin, J. Morre,
M.L. Deinzer, C. Woodward, and P.D. Collin, Can. J. Chem. 85, 626 (2007).
[2] A.S. Silchenko, A.I. Kalinovsky, S.A. Avilov, P.V. Andryjaschenko, P.S. Dmitrenok, V.I.
Kalinin, E.A. Martyyas, and K.V. Minin, Nat. Prod. Commun. 11, 939 (2016).
[3] A.S. Silchenko, A.I. Kalinonovsky, S.A. Avilov, P.V. Andryjashenko, P.S. Dmitrenok,
V.I. Kalinin, and V.A. Stonik, Biochem. Syst. Ecol. 44, 53 (2012).
[4] X.M. Zhang, X.B. Li, S.S. Zhang, Q.X. He, H.R. Hou, L. Dang, J.L. Guo, Y.F. Chen, T.
Yu, D.J. Peng, L.W. Han, and K.C. Liu, Chem. Nat. Compd. 54, 721 (2018).
[5] F. Mohammadizadeh, M. Ehsanpor, M. Afkhami, A. Mokhlesi, A. Khazaali, and S.
Montazeri, J Mycol Med. 23, 225 (2013).
[6] Y. Bahrami, W. Zhang, and C. Franco, Mar. Drugs. 12, 225(2014).
[7] D.L. Aminin, E.S. Menchinskaya, E.A. Pislyagin, A.S. Silchenko, S.A. Avilov, and V.I.
Kalinin, Mar. Drugs. 13, 1202 (2015).
[8] D.L. Aminin, E.A. Pislyagin, E.S. Menchinskaya, A.S. Silchenko, S.A. Avilov, and V.I.
Kalinin, Stud. Nat. Prod. Chem. 41, 75 (2014).
[9] N. Sarhadizadeh, M. Afkhami, and M. Ehsanpour, Eur. J. Exp. Biol. 4, 254 (2014).
[10] N.B. Janakiram, A. Mohammed, and C. Rao, Mar. Drugs. 13, 2909 (2015).

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
9
[11] S.N. Fedorov, S.A. Dyshlovoy, A.S. Kuzmich, L.K. Shubina, S.A. Avilov, A.S. Silchenko,
A.M. Bode, Z. Dong, and V.A. Stonik, Nat. Prod. Commun. 11, 1239 (2016).
[12] A.S. Silchenko, A.I. Kalinovsky, S.A. Avilov, V.I. Kalinin, P.V. Andrijaschenko, P.S.
Dmitrenok, E.A. Chingizova, S.P. Ermakova, O.S. Malyarenko, and T.N. Dautova, Mar.
Drugs. 15, 256 (2017).
[13] A.S. Silchenko, A.I. Kalinovsky, S.A. Avilov, V.I. Kalinin, P.V. Andrijaschenko, P.S.
Dmitrenok, E.A. Chingizova, S.P. Ermakova, O.S. Malyarenko, and T.N. Dautova, Nat.
Prod. Commun. 12,1577 (2017)
[14] M. Amakura, M. Yoshimura, S. Morimoto, T. Yoshida, A. Tada, Y. Ito, T. Yamazaki,
N. Sugimoto, and H. Akiyama, Chem. Pharm. Bull. 64, 78 (2016).
[15] D.L. Liu, Y. Yang, Q. Liu, and J.J. Wang, Med. Oncol. 28, 105 (2011).