Molekul, Vol. 20. No. 2, July 2025: 382 – 393

Articles

MOLEKUL
eISSN: 2503-0310

https://doi.org/10.20884/1.jm.2025.20.2.16066

Chemical Constituents from Indonesian Dysoxylum parasiticum (Osbeck). Kosterm and Their Cytotoxicity
Against MCF-7 Breast Cancer Cells
Harizon1*, Febbry Romundza, Isra Miharti, Al Arofatus Naini2, Sofa Fajriah2,
Tri Mayanti3, Unang Supratman3,4
Faculty of Teacher Training and Education, Universitas Jambi, Mendalo Indah, Jambi 36361, Indonesia
Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation
Agency (BRIN), Cibinong Science Center Complex – BRIN, Cibinong 16911, Bogor, West Java, Indonesia
3
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran,
Jatinangor 45363, Sumedang, West Java, Indonesia
4
Central Laboratory, Universitas Padjadjaran, Jatinangor 45363, Sumedang, West Java, Indonesia
1

2

*Corresponding author email: harizon@unja.ac.id
Received June 12, 2025; Accepted July 17, 2025; Available online July 20, 2025

ABSTRACT. The exploration of naturally occurring secondary metabolites from plants, which serve as direct sources or
precursors for new drug development, motivates us to conduct a comprehensive investigation into their presence. Indonesia
stands out as a global biodiversity hotspot, boasting a significant number of endemic species that offer a rich reservoir of
untapped resources for pharmaceutical, agricultural, and environmental uses. The Dysoxylum genus, belonging to the
Meliaceae family, is recognized as a vital source of secondary metabolites and is well-known for its traditional medicinal
applications. Consequently, we focus on analyzing the chemical constituents found in the stem bark of one Indonesian
Dysoxylum species, specifically D. parasiticum (Osbeck) Kosterm., and assess their biological activity as anticytotoxic agents.
Our research identified three known compounds: a tirucallane-type triterpenoid, cneorin-NP36 (1), a seco-limonoid from the
preurianin group, amotsangin A (2), and an ergostane-type steroid, 22(E)-ergosta-6,22-dien-3β,5α,8α-triol (3). The
biological evaluation against the human breast cancer cell line MCF-7 revealed that compound 2 exhibited a notable
inhibitory effect, with an IC50 value of 34.5 μM. The existence of a highly oxidized structure in compound 2, due to its ester
substituents, highlights its effectiveness in inhibiting cancer cell proliferation, outperforming the reference drug cisplatin,
which has an IC50 of 53.0 μM. These findings indicate that amotsangin A (2) is a promising anticancer agent, particularly in
the treatment of breast cancer. Further studies, including in silico analysis and structural modification, are needed to enhance
its cytotoxic activity and selectivity.
Keywords: Cytotoxic activity, Dysoxylum parasiticum, MCF-7, seco-limonoid amotsangin A, Secondary metabolites

INTRODUCTION
The Dysoxylum genus serves as a significant source
of secondary metabolites. Part of the Meliaceae family,
this genus includes around 200 species predominantly
located in Australia, New Zealand, India, and
Southeast Asia (Lakshmi et al., 2009; Naini et al.,
2022b; Xu et al., 2013; Huang, et al., 2011; Wang &
Guan, 2012; Hu et al., 2014; Yan et al., 2021). The
Meliaceae, commonly referred to as Mahogany,
consists of plants characterized by their woody
structure, making this family renowned for its
production of high-quality timber (Atkinson, 2020).
Additionally, this family is noted for its wood, which
emits a distinctive aroma (Riyadi et al., 2023; Tan et
al., 2011; Naini et al., 2022a; Naini et al., 2023a).
Historically, these plants have been employed as
traditional remedies by indigenous populations in Asia
to treat various ailments, such as D. binectariferum
and D. lourieri for skin conditions and ulcers (Hu et

al., 2014; Yan et al., 2021; Kumar at al., 2016;
Sarkar & Devi, 2017; Ashwell & Walston, 2008;
Chanda et al., 2007; Bourdy et al., 1996), D.
gaudichaudianum leaves for a range of pains and
respiratory issues (Sarkar & Devi, 2017; Ashwell &
Walston, 2008; Chanda et al., 2007; Nagakura.,
2010; Jian et al., 2007; Lalmuanpuii et al., 2013),
and D. richii for joint stiffness and skin irritations
(Ashwell & Walston, 2008; Chanda et al., 2007;
Bourdy et al., 1996; Jogia & Andersen, 1987; Singh
& Aalbersberg, 1992). In Indonesia, numerous
species have been identified and cultivated, many
of which yield novel compounds, including
triterpenoids, limonoids, steroids, and macrolides,
and some exhibiting moderate activity against
human cancer cells (Naini et al., 2022a; Niani et
al., 2023a; Naini et al., 2023b; Riyadi et al., 2024a;
Riyadi et al., 2024c; Kautsari et al., 2024a; Naini et
al., 2024b).

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Chemical constituents from Indonesian Dysoxylum parasiticum (Osbeck).

Dysoxylum parasiticum (Osbeck) Kosterm.
(Meliaceae) is a large tree species that can reach
heights up to 38 meters and is commonly known as
the aromatic tree or "Majegau". This species is
extensively cultivated, especially in West Java and Bali,
and holds cultural significance for various indigenous
ethnic groups. Phytochemical investigations of this
plant have uncovered a substantial presence of
terpenoids, which show immunomodulatory effects on
TLR4 and possess cytotoxic properties. Key compounds
identified include sesquiterpenoids and their
oligomers (Naini et al., 2023a; Naini et al., 2023b;
Naini et al., 2024b;), triterpenoids (Naini et al.,
2022a), limonoids (Naini et al., 2024a), and phenolic
derivatives (Sofian et al., 2022). As part of our
ongoing
research
into
bioactive
secondary
metabolites, we examined the chemical constituents of
the stem barks of D. parasiticum. This study identified
three known compounds: a tirucallane-type
triterpenoid, cneorin-NP36 (1), a seco-limonoid from
the preurianin group, amotsangin A (2), and an
ergostane-type steroid, 22(E)-ergosta-6,22-dien3β,5α,8α-triol (3). The structures of the compounds
were elucidated using high-resolution mass
spectrometry (HRMS), infrared spectroscopy (IR), onedimensional (1D) and two-dimensional (2D) nuclear
magnetic resonance (NMR), along with comparisons
to previously reported data.
EXPERIMENTAL
General Experimental Procedures
NMR data were acquired using JEOL ECZR 500
NMR (JEOL USA, Inc., USA) spectrometer. Highresolution mass spectrometry (HR-MS) was performed
with a Waters Xevo Quadrupole-TOF-MS/direct probe
(Milford, MA), operating in ESI+ mode. Infrared

Harizon, et al.

spectra were recorded using Everest ATR Thermo
Scientific (Thermo Fisher Scientific, Madison, WI, USA).
The melting point values were determined using a
BUCHI M-565 melting point apparatus (BUCHI Corp.,
Switzerland). For column chromatography (CC), silica
gel (230–400 and 70-230 mesh) and Octadecyl
silane (100-200 mesh) were sourced from Merck
(Germany) and Fuji Sylisia Chemical LTD. (Japan).
Thin layer chromatography (TLC) was conducted using
silica gel GF254 and RP-18 F254s plates, both obtained
from Merck. The TLC analysis was performed under
ultraviolet light and subsequently visualized using a
10% H2SO4/EtOH solution, followed by a heating
process.
Plant Material
The stem barks of Dysoxylum parasiticum (Osbeck)
Kosterm (Figure 1). were gathered from the Bogor
Botanical Garden (BBG) located in West Java
Province, Indonesia. The botanical specimen
underwent morphological authentication by Mr. Harto
from the BBG Herbarium and was designated the
voucher specimen with barcode III. F.79.
Extraction and Isolation
The dried and powdered stem bark (5.5 kg)
underwent extraction with methanol (3 x 12 L) at room
temperature, with each extraction period extending for
24 hours. The partitioning procedure was detailed in
earlier studies, which included the initial phase of
chromatographic separation of the n-hexane extract
(153.9 g), yielding eight primary fractions labeled Fr.
A to Fr. L [11,12,23,27]. Fraction D, weighing 40.9
g, underwent column chromatography using silica gel
(70–230 mesh) with a gradient elution of n-hexane
and EtOAc (10:0 to 7:3, 5% v/v), resulting in the
isolation of nine additional fractions designated as Fr.
D1 through Fr. D9.

(A)
(B)
Figure 1. Dysoxylum parasiticum (Osbeck) Kosterm. (A) and stem barks (B) (Private Photograph Courtesy).
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Molekul, Vol. 20. No. 2, July 2025: 382 – 393
Subsequently, Fraction D7, weighing 5.0 g, was
further
purified
using
silica
gel
column
chromatography (70–230 mesh) and eluted with a
mixture of n-hexane and EtOAc (10:0 to 5:5, 2.5%
v/v), yielding eight subfractions labeled D7a to D7h.
Subfraction D7a, weighing 800 mg, was then
subjected to column chromatography on silica gel
(230–400 mesh), eluted with a solvent system of nhexane, dichloromethane, and EtOAc (7:2:1), and
subsequently refined using flash ODS reversed-phase
column chromatography with a MeOH–H2O mixture
(8:2), ultimately producing compound 1 in a yield of
7.1 mg. Subfraction D7b (300 mg) was subjected to
separation using silica gel (230–400 mesh) with an
eluent mixture of n-hexane and EtOAc (10:1). The
resulting product was further purified through ODS
column chromatography employing a MeOH and
H2O mixture (8:2), yielding compound 3 (4.0 mg).
Furthermore, fraction D9 (2.0 g) was applied to a silica
gel column (230–400 mesh) and eluted using a
mixture of CH2Cl2 and EtOAc (10:0 to 5:5, 10% v/v),
resulting in the separation of six subfractions
designated as D9a through D9f. Subfraction D9d (300
mg) underwent purification via flash ODS column
chromatography using a MeOH–H2O solvent system
(8:2), yielding compound 2 (15.1 mg).
Cytotoxic Assay
A cytotoxicity assay was conducted following
established protocols (Kautsari et al., 2024b; Riyadi et
al., 2024b). The isolated compounds (1–3) were
assessed for their cytotoxic effects on human breast
cancer cell lines (MCF-7) utilizing RPMI-1640 medium
enriched with 10% fetal bovine serum (FBS) and 1%
antibiotics. After a 24-hour incubation period, cell
viability was determined using Prestoblue™ reagent,
with measurements taken at 570 nm using a
microplate reader.
RESULTS AND DISCUSSION
The phytochemical investigation of Dysoxylum
parasiticum (Osbeck). Kosterm stem barks isolated
from n-hexane extract yielded one tirucallane-type
triterpenoid, cneorin-NP36 (1), one preurianine-type
limonoid, amotsangin A (2), one ergostane-type
steroid, 22(E)-ergosta-6,22-dien-3β,5α,8α-triol (3),

and one coumarin-type phenylpropanoid, scopoletin
(4). The isolation and purification were performed by
a combination of chromatography techniques
between normal and reversed phases, as well as
utilizing a thin layer chromatography (TLC) with
universal sprayer reagent of H2SO4 in 10% EtOH.
Cneorin-NP36 (1), was isolated as a white
crystalline material. The molecular formula was
determined to be C30H46O3, with the molecular ion
peak observed in HR-ESI-QTOFMS at m/z 455.3596
[M + H]+ (calculated for C30H47O3, 455.3678),
indicating eight degrees of unsaturation. The NMR
analysis of compound 1 revealed a tetracyclic
triterpenoid framework, featuring one secondary
methyl group at δH 1.04 (3H, d, J = 6.5 Hz), seven
tertiary methyl groups at δH 0.77; 0.99; 1.03; 1.03;
1.09; 1.32; 1.32; 1.39 ppm, and four nonoxygenated aliphatic quaternary carbons at δC 35.1;
43.9; 50.8; and 58.4 ppm. The HMQC analysis
indicated the presence of typical double bond signals
attributed to the fragment C-7/C-8 [-CH=C=] at δC
118.4 (δH 5.35, 1H, td, J = 3.5, 3.5 Hz) and 145.7
ppm, suggesting a tirucallane-type skeleton. This
assignment was proved by the HMBC correlations
from H3-30 (δH 1.03); H-9 (δH 2.32); H-7 (δH 5.35); H6 (δH 2.06 and 2.78); to C-8 (δC 145.7) and vicinal
cross-peaks of the B-ring fragment (H-5/H-6/H-7) in
the 1H-1H COSY spectrum. In addition to the
characteristics of tirucallane skeleton with a double
bond pair at C-7/C-8, the position of vicinal dimethyl
group at C-13 and C-14 was further assigned based
on the HMBC correlations of H3-18 (δH 0.99) and H330 (δH 1.03) to C-13 (δC 43.9) and C-14 (δC 50.8).
The ketone carbonyl group at δc 216.9 ppm was also
observed in 1, where the position of the oxygenated
carbon at C-3 was determined based on the
biogenesis pathway of the triterpenoid compound
derived from 2,3-epoxy squalene and convinced by
HMBC correlations of H3-28 (δH 1.09) and H3-29 (δH
1.03) to C-13 (δC 43.9) and C-14 (δC 50.8).
Furthermore, the HMBC correlations of H 3-19 (δH
0.99) to C-1 (δC 38.5); C-5 (δC 52.3); C-9 (δC 48.4);
and C-10 (δC 35.1) completed the A-ring fragment in
the tetracyclic system of tirucallane-type triterpenoid in
compound 1.

Figure 2. Structure of chemical constituents of D. parasiticum (Osbeck) Kosterm. stem barks 1-3.
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Chemical constituents from Indonesian Dysoxylum parasiticum (Osbeck).

Analysis of the 2D NMR above implies that
compound 1 had two additional cyclic to meet the
value of unsaturation degrees from the MS data. The
presence of four oxygenated carbons, including three
methines [δC 60.5/C-22 (δH 2.60, 1H, dd, J=8.0; 2.5
Hz), 57.5/C-23 (δH 2.78, 1H, dd, J=6.5 1.8 Hz),
63.2/C-24 (δH 2.55, 1H, d, J=6.4 Hz)] and one
quaternary group [δC 58.4/C-225], was assumed to
form two epoxy rings in the side chain. The 1H-1H
COSY correlations of coupling-coupling system from
H3-21/(H-20)/H-22/H-23/H-24 and 3JH-C interactions
of H3-26 (δH 1.39) and H3-27 (δH 1.32) to C-25 (δC
58.4) and C-24 (δC 63.2) placed the two adjacent
epoxy rings at C-22-O-C-23 and C-24-O-C-25,
respectively. Thus, the planar structure of 1 was fully
constructed based on the NMR data, as shown in
Figure 3. As tirucallane-type triterpenoid possesses the
same planar structure as its C-21 stereoisomer, i.e.,
euphane-type (Huang et al., 2011; Hill & Connolly,
2017; Sawai & Saito, 2011; Zhang et al., 2010; Liu et
al., 2001), the stereochemistry of 1 needs to be
deduced. A NOESY experiment was subsequently
carried out to determine the relationship between each
stereocenter carbon and its surrounding space. The
NOE correlations observed between H3-19/H3-29, H17/H3-30, and H-17/H3-21 as β-oriented protons,
along with α-proton correlations of H3-28/H-5, H-

Harizon, et al.

9α/H3-18, and H3-18/H-20, aligned with that of the
tirucallane skeleton, in particular the β-orientation of
the secondary methyl group at C-21 (Figure 4). The
correlations among the proton-proton interactions of
the asymmetrical carbon in the side chain can be
detected in the NOESY spectrum; however, the free
rotation and vicinal positioning of the two epoxy rings
invalidate this information, necessitating an alternative
approach. The NMR data for compound 1 were
subsequently compared with the previously identified
compound cneorin-NP36, as first reported by Gray and
co-workers (see Table 1) (Gray et al., 1988). The
analysis revealed that both compounds exhibited
identical chemical shifts, indicating that compound 1
possesses a planar structure with the orientations of H22, H-23, and H-24 configured as β. In cyclic epoxide
systems, cis-conformational vicinal protons typically
exhibit coupling constant values ranging from 7 to
12.6 Hz; however, in compound 1, the 2J values for
H-22/H-23 were measured at 8.0; 2.5 and 6.5; 1.8
Hz, respectively. Furthermore, Wang et al. provided a
revised structure for cneorin-NP36, indicating that H-23
is oriented α, with an absolute configuration of 22S*,
23S*, and 24S* determined through X-ray diffraction
analysis (Wang et al., 2011). Consequently,
compound 1 was identified and confirmed as the
corrected form of cneorin-NP36 (Figure 2).

Figure 3. 1H-1H COSY and HMBC correlations of 1 and 2.

Figure 4. 1H-1H NOESY correlations of 1 and 2
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Molekul, Vol. 20. No. 2, July 2025: 382 – 393
Table 1. NMR data (1H and 13C-NMR, CDCl3) of 1 with literature (13C-NMR, CDCl3)
No.

H NMR (ΣH, mult., J Hz)
1.98 (1H, ddd, 13.0; 5.5;
3.5)
1.46 (1H, m)
2.23 (1H, dt, 14.5; 3.5)
2.78 (1H, td, 14.5; 5.5)
1.75 (1H, m)
2.06 (1H, m)
2.25 (1H, m)
5.35 (1H, td, 3.5; 3.5)
2.32 (1H, m)
1.58 (1H, m)
1.64 (1H, m)
1.85 (1H, m)
1.54 (1H, m)
1.35 (1H, m)
1.98 (1H, m)
1.70 (1H, m)
0.77 (3H, s)
0.99 (3H, s)
1.28 (1H, m)
1.04 (3H, d. 6.5)
2.60 (1H, dd, 8.0; 2.5)
2.78 (1H, dd, 6.5; 1.8)
2.55 (1H, d, 6.4)
1.39 (3H, s)
1.32 (3H, s)
1.09 (3H, s)
1.03 (3H, s)
1.03 (3H, s)
1

1.
2.
3
4.
5.
6.
7.
8.
9
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.

C NMR (mult.)
38.5 (t)

Cneorin-NP36 (CDCl3).
(Gray et al., 1988; Wang et al., 2011)
13
C NMR (mult.)
38.4 (t)

34.9 (t)

34.7 (t)

216.9 (s)
47.9 (s)
52.3 (d)
24.4 (t)

216.4 (s)
47.7 (s)
52.2 (d)
24.3 (t)

118.4 (d)
145.7 (s)
48.4 (d)
35.1 (s)
18.2 (q)
33.3 (t)

118.1 (d)
145.3 (s)
48.3 (d)
34.9 (s)
18.0 (q)
33.2 (t)

43.9 (s)
50.8 (s)
34.2 (d)
27.5 (t)

43.8 (s)
50.7 (s)
34.1 (d)
27.3 (t)

50.5 (d)
12.8 (q)
21.6 (q)
39.1 (d)
16.6 (q)
60.5 (d)
57.5 (d)
63.2 (d)
58.4 (s)
19.7 (q)
24.8 (q)
24.6 (q)
21.6 (q)
27.6 (q)

50.4 (d)
12.6 (q)
21.4 (q)
39.0 (d)
16.3 (q)
60.3 (d)
57.3 (d)
63.2 (d)
58.2 (s)
19.5 (q)
24.6 (q)
24.5 (q)
21.4 (q)
27.4 (q)

Compound 1 (CDCl3)
13

Amotsangin A (2), was isolated as an optically
active white crystalline substance, exhibiting a specific
rotation of [α]D25 +108.5. Additionally, it displayed a
bathochromic shift in its UV absorption spectrum, with
absorption maxima recorded at 218 nm. Highresolution electrospray ionization mass spectrometry
(HRESIMS) analysis shows the molecular formula as
C34H44O10 at m/z 635.2841 [M + Na]+ (calculated
for C34H44O10Na, m/z 635.2832), manifesting 13
degrees of unsaturation. The infrared (IR) spectrum
revealed the presence of various functional groups,
including CH sp3 (2978 cm-1), carbonyl ester (1751
cm-1), conjugated carbonyl ester (1697 cm-1), C=C
(1644 cm-1), gem-dimethyl (1462, 1431 cm-1) and CO (1233 cm-1. The 1H NMR (Table 2) suggested a set
of furan group shifts [δH 7.25 (1H, s), 7.07 (1H, s) and

6.17 (1H, s) ppm], one methoxy at δH 3.69 (3H, s)
ppm, one acetyl [δH 2.08 (3H, s) ppm], four tertiary
methyls [δH 1.52 (3H, s), 1.25 (3H, s), 1.52 (3H, s),
0.96 (3H, s), and 0.93 (3H, s) ppm], and one primary
methyl at δH 0.73 (3H, t, J = 7.3 Hz) ppm. The 13C
NMR and DEPT of compound 2, together with the
HMQC spectra displayed the presence of a total of 34
carbons, including four carbonyl esters (one
conjugated) [δC 175.0; 173.5; and 166.5 ppm], eight
sp2 carbons (one methylene, five methine and two
quaternary carbons), 22 aliphatic carbons (comprising
two oxygenated quaternary carbons, three oxygenated
methins and one methoxy). The presence of one furan
ring, three olefinic bonds and four carboxyls was
calculated as nine degrees of unsaturation, so a
tetracyclic skeleton is required to satisfy the

386

Chemical constituents from Indonesian Dysoxylum parasiticum (Osbeck).
unsaturation degree values. The presence of two nonoxygenated aliphatic quaternary carbons [δC 46.2 (C10) and 45.6 (C-13) ppm] and one methylene sp2 [δC
120.8 (C-30) ppm] indicated the presence of a seco
group (modified ring) with two intact rings of the
limonoid compound. Analysis of 3JH-C correlations
through an HMBC experiment indicated the presence
of seco-A,B ring groups through the correlation of H328 (δH 1.25)/H3-29 (δH 1.55) to C-4 (δC 83.5), C-5
(δC 50.3) and H-30 (δH 5.17 and 5.34) to C-8 (δC
136.9), C-9 (δC 53.4), C-14 (δC δc 71.1). HMBC
correlations of H3-19 (δH 0.96) to C-1 (δC 148.5), C10 (δC 46.2) coupled with H-1/H-2 correlation at 1H1
H COSY confirmed the α,β-unsaturated-εcaprolactone fragments in ring A, while open ring B
was evidenced from long-range interractions of -OMe
(δH 3.66)/H-5 (δH 3.25) with C-7 (δC 173.5). The intact
C,D-ring was determined based on the correlation of
H3-18 (δH 0.93) to C-12 (δC 73.6), C-13 (δH 43.6), C17 (δH 42.7) and H-16 (δH 5.46)/H3-18 (δH 0.93) to C14 (δH 71.1), as well as the two vicinal proton
segments of H-9/H-11/H-12 and H-15/H-16/H-17.
The presence of epoxy group located at C-14 (δC
71.1)/C-15 (δC 59.4) was determined to satisfy the
one remaining degree of unsaturation in conjuction
with the MS data. Thus, a preurianin-type limonoid
matches with the main skeleton in compound 2. The
remaining signals and observed correlations,
including H-2' (δH 1.89)/H-12 (δH 5.81) to C-1' (δC
175.0) and H-2'' (δH 2.08)/H-11 (δH 5.60) to C-1'' (δC
170.4), established the substitution of 2methylbutoyloxy and ecetoxy at C-12 and C-11,
respectively (Figure 3).
A NOESY experiment was consequently performed
to deduce the relative configuration in 2 (Figure 4).
Notable cross-peaks were observed between H-5/α
and H-9/H3-28, as well as between H-9 and H-11,
indicating a co-facial relationship among these
protons. In contrast, H3-29 and the acyloxy group at
C-11 are positioned oppositely. The single bond
linking C-9 and C-10, along with the surrounding
structures, is notably congested, which may lead to
stereochemical complications. A comparison of NMR
data for compound 2 with existing literature on
preurianin and related compounds has established the
orientation of H-5 and H-9 as proton-α, supported by
NMR analysis conducted at non-ambient temperatures
and X-ray diffraction studies (Vincent et al., 1975).
Additionally, the correlation between H-12 and H-17,
as well as H-11 and H3-18, suggested that these
proton pairs are situated on the same side, with H12/H-17 exhibiting a β orientation and H-11/H3-18
displaying an α orientation, thereby confirming a 1,2diaxial relationship between H-11/H-12. As a result,
the 2-methylbutanoyloxy group located at C-12 and
the furan ring at C-17 are positioned towards the α
side, while the acyloxy group at C-12 is directed
towards the β side. The β orientation of the 14,15-

Harizon, et al.

epoxide was established through the correlation of H 318/α with H-30a, H-30a with H-15 (Govindachari et
al., 1999; Maclachlan & Taylor, 1982). Further
comparison of 1D-NMR data of 2 with amotsangin A
reported from the same family Meliaceae, showed that
they have identical chemical shifts (Table 2) (Chen et
al., 2008). Hence, the structure of 2 was then
identified and designated as amotsangin A, shown in
Fig. 2. It is important to note that amotasangin A (2),
a highly oxidized seco-limonoid compound, , is
reported for the first time from the genus Dysoxylum,
specifically from D. parasiticum. Although structurally
related limonoids have previously been identified
within the Meliaceae family, including other
Dysoxylum species (Naini et al., 2024b), this discovery
broadens the known structural diversity of secondary
metabolites in D. parasiticum and enriches the
phytochemical profile of the genus Dysoxylum.
22(E)-ergosta-6,22-dien-3β,5α,8α-triol (3), was
obtained as a white powder. The molecular formula
was established as C28H46O3 by its HR-QTOFMS/ESI+,
m/z 453.3351 (calculated for. m/z 453.3345, [M +
Na]+), referencing to six unsaturated degrees. The 1HNMR data of 3 showed six methyl resonances,
involving two tertiary groups [δH 0.87 (3H, s) and 0.89
(3H, s) ppm] and four secondary methyls [δH 0. 81
(3H, d, J = 6.5 Hz), 0. 84 (3H, d, J = 6.5 Hz), 0. 93
(3H, d, J = 6.1 Hz), 1.01 (3H, d, J = 6.5 Hz) ppm].
Similar to those of isolated compounds 1 and 2, the
structure elucidation of 3 was therefore supplemented
by 13C-NMR and DEPT experiments, generating 28
carbon resonances. The two non-oxygenated
quaternary carbons (δC 37.0 and 44.6 ppm) aligned
with the existance of two tertiray methyls, as well as
four secondary methyl groups (CH3-21, CH3-26, CH327, and CH3-28) located in the side chain, indicated
that compound 3 is an ergostane-type steroid. An
ergostane-type steroid is characterized by the
presence of an extra secondary methyl group [δC 20.9
(δH 1.01, d, 6.5 Hz)] at the C-24 position, in addition
to a notable double bond of -CH=CH- found between
C-22 [δC 132.2 (δH 5.18, m) ppm] and C-23, [δC
135.7 (δH 5.22, m) ppm]. Moreover, the existance of
a second paired olefinic bond characterized by the CH=CH- fragment at [δC 135.4 (δH 6.60, m) and
130.7 (δH 6.33, m) ppm] was attributed to the C-6/C7 system, similar to other ergostane-type steroids
derived from the Meliaceae family. The presence of
hydroxyl methine resonances at δC 66.5 (δH 3.95, m)
was inferred to be located at C-3, based on the
biogenetic perspective of steroids derived from 2,3epoxy squalene. The two remaining oxygenated
nonprotonated carbon groups observed at δC 82.2
and 79.4 ppm were assigned to C-5 and C-8,
respectively, contributing to the formation of a diol
group. This assignment is supported by the mass
spectrum data and the characteristics of related

387

Molekul, Vol. 20. No. 2, July 2025: 382 – 393

Table 2. NMR data (1H and 13C-NMR, CDCl3) of 2 with literature (13C-NMR, CDCl3)
No.
1.
2.
3.
4.
5.
6a
6b.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
28.
29.
30a
30b.
OMe.
1’.
2’.
3a’.
3b’.
4’.
5’.
1”.
2”.

Compound 2 (CDCl3)
H NMR (ΣH, mult., J Hz)
6.89 (1H, d, 13.0)
6.22 (1H, d, 13.1)
3.25 (1H, d, 9.0)
2.14 (1H, dd, 16.5; 9.2)
2.24 (1H, d, 16.6)

1

3.02 (1H, d, 7.2)
5.60 (1H, dd, 10.9; 7.1)
5.81 (1H, d, 10.9)
3.88 (1H, s)
2.24 (1H, dd, 14.0, 7.0)
1.83 (1H, dd, 14.0)
0.93 (3H, s)
0.97 (3H, s)
7.07 (1H, s)
6.16 (1H, s)
7.25 (1H, s)
1.25 (3H, s)
1.52 (3H, s)
5.17 (1H, s)
5.34 (1H, s)
3.68 (3H, s)
1.89 (2H, m)
1.17 (1H, m)
1.41 (1H, m)
0.73 (3H, t, 7.3)
0.79 (3H, d, 8.4)
2.08 (3H, s)
-

13

Amotsangin A (CDCl3) (Chen et al., 2008)

C NMR (mult.)
148.5 (d)
122.0 (d)
166.5 (s)
83.5 (s)
50.1 (d)
35.0 (t)

13

C NMR (mult.)
148.5 (d)
122.0 (d)
166.5 (s)
83.5 (s)
50.0 (d)
34.9 (d)

173.5 (s)
136.9 (s)
53.4 (d)
46.2 (s)
71.0 (d)
73.6 (d)
45.6 (s)
71.1 (s)
59.6 (d)
34.1 (t)

173.5 (s)
136.7 (s)
53.2 (d)
46.2 (s)
70.9 (d)
73.6 (d)
45.5 (s)
71.0 (s)
59.0 (d)
34.0 (t)

42.7 (d)
13.6 (q)
22.7 (q)
122.0 (s)
140.6 (d)
111.2 (d)
142.3 (d)
30.3 (q)
22.4 (q)
120.8 (t)

37.6 (d)
13.6 (q)
22.7 (q)
122.1 (s)
140.5 (d)
111.3 (d)
142.3 (d)
30.2 (q)
22.3 (q)
120.8 (t)

52.3 (q)
175.0 (s)
40.5 (t)
25.7 (t)

52.3 (q)
175.0 (s)
41.1 (t)
25.9 (t)

11.4 (q)
15.2 (q)
170.4 (s)
20.7 (q)

11.7 (q)
15.3 (q)
170.4 (s)
20.6 (q)

ergostane compounds that exhibit significant oxidation
at these carbon positions. The determination of the
structure for compound 3 was achieved through a
limited set of experiments; however, the analysis of the
resonances observed in the 1H and 13C-NMR data was
sufficiently reliable to enable the complete construction
of its structure. A subsequent literature review
indicated that the 1D-NMR data for compound 3
exhibited significant similarities to 22-(E)-ergosta6,22-dien-3β,5α,8α-triol (Table 3), which was derived
from the ethanolic extract of Letinus edodes (Shiitake)
(Rivera et al., 2009). To our knowledge, 22(E)ergosta-6,22-dien-3β,5α,8α-triol (3) (Figure 2), a
polyhydroxylated ergostane-type steroid, is reported

for the first time from D. parasiticum. This discovery
contributes to the phytochemical profile of D.
parasiticum and enriches the diversity of its secondary
metabolites, particularly within the steroid class.
Activity against Breast Cancer MCF-7
In order to evaluate the biological activity of three
identified compounds, they were tested against the
human breast cancer MCF-7. Recent findings
published by the World Health Organization (2018)
indicate that breast cancer cases in Indonesia have
reached unprecedented levels, accompanied by the
second-highest mortality rate. Concurrently, the issue
of drug resistance in MCF-7 cancer cells persists. This
phenomenon is attributed to the luminal A subtype of

388

Chemical constituents from Indonesian Dysoxylum parasiticum (Osbeck).
breast cancer cells, such as MCF-7, which, accounting
for approximately 70% of cases, exhibit the expression
of alpha estrogen receptors (ER-α). These receptors
contribute to resistance against several chemotherapy
agents, including doxorubicin (Lovitt et al., 2018;
Chekhun et al., 2006; Fang et al., 2014; Chen et al.,
2010), paclitaxel (Zhang et al., 2015; Pavlíková et al.,
2015; Armat et al., 2016), tamoxifen (Yao et al.,
2020; To et al., 2022; Zhang et al., 2015), and
cisplatin (Kobayashi et al., 2022; Ruiz-Silvestre et al.,
2024; Chen et al., 2016). Therefore, the exploration
of natural materials for compounds exhibiting
cytotoxic effects on MCF-7 cells continues to represent
a promising avenue for the development of anticancer
agents characterized by enhanced chemosensitivity.
As shown in Table 4, among all three compounds 13, compounds 1 and 3 showed no activity with their
IC50 values over 100 μM, while compound 2 displayed
more inhibitory effect with its IC50 value of 34.5 μM
than the reference drug cisplatin (IC 50, 53.0 μM).
According to the previous results, compound 2

Harizon, et al.

possessed a potent antiviral against tobacco mosaic
virus (Yan et al., 2015), while its cytotoxicity is reported
for the first time in this work, unless the analog,
paraxyline A, with modest cytotoxicity against MCF-7
and HeLa cells (Naini et al., 2024b). These results are
also consistent with those observed for 1, which
showed no inhibitory activity against human lung
cancer A549 cells (Riyadi et al., 2024d), and 3, which
was inactive against MCF-7 and HeLa cells (Naini et
al., 2024b). The presence of highly modified
limonoids, characterized by an opening in the A and
B rings and significant substitution by ester derivatives
at position 2, may be essential in the fight against
human cancer cells, despite the variation in their
primary skeletal structures. Regardless of they all have
different main skeletons and the structure activityrelationship (SAR) could not be explored, the
occurrence of highly modified limonoids with an
opening in the A, B-rings and highly substituted by
ester derivatives in 2 might be necessary against
human cancer cells.

Table 3. NMR data (1H and 13C-NMR, CDCl3) of 3 with literature (13C-NMR, CDCl3)

No.
1

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.

C NMR (mult.)
34.2 (t)

22(E)-ergosta-6.22-dien3β,5α,8α-triol (CDCl3) (Rivera
et al., 2009)
13
C NMR (mult.)
34.7 (t)

39.3 (t)

39.3 (t)

66.5 (d)
36.9 (t)
82.2 (s)
135.4 (d)
130.7 (d)
79.4 (s)
51.7 (d)
37.0 (s)
20.6 (t)
30.1 (t)
44.6 (s)
55.9 (d)
22.9 (t)
28.6 (t)
33.1 (d)
12.9 (q)
18.2 (q)
42.8 (d)
17.6 (q)
132.2 (d)
135.7 (d)
39.7 (d)
51.5 (d)
19.9 (q)
19.6 (q)
20.9 (q)

66.5 (d)
36.9 (t)
82.2 (s)
135.4 (d)
130.7 (d)
79.4 (s)
51.7 (d)
37.0 (s)
20.6 (t)
30.1 (t)
44.6 (s)
56.2 (d)
23.4 (t)
28.6 (t)
33.1 (d)
12.9 (q)
18.2 (q)
42.8 (d)
17.6 (q)
132.3 (d)
135.2 (d)
39.7 (d)
51.1 (d)
19.9 (q)
19.6 (q)
20.9 (q)

Compound 3 (CDCl3)
H NMR (ΣH, mult., J Hz)
1.96 (1H, m)
1.69 (1H, m)
1.99 (1H, m)
1.24 (1H, m)
3.95 (1H, m)
1.92 (2H, m)
6.60 (1H, m)
6.33 (1H, m)
1.59 (1H, m)
1.62 (2H, m)
1.52 (2H, m)
1.19 (1H, m)
1.22 (2H, m)
1.23 (2H, m)
1.51 (1H, m)
0.87 (3H, s)
0.89 (3H, s)
1.82 (1H, m)
0.93 (3H, d, 6.4)
5.18 (1H, m)
5.22 (1H, m)
2.02 (1H, m)
1.85 (1H, m)
0.84 (3H, d, 6.5)
0.81 (3H, d, 6.5)
1.01 (3H, d, 6.5)

13

389

Molekul, Vol. 20. No. 2, July 2025: 382 – 393
Table 4. Cytotoxic activity of 1-3 against human cancer cell
lines (IC50 ± SD, µM)a
Compounds
MCF-7
1
>100
2
34.5 ± 2.1
3
>100
Cisplatinb
53.0 ± 0.1
a
Data were reported as the mean ± SD; n = 3 independent replicates
b
Positive control
Among the three tested compounds, only
amotsangin A (2) demonstrated notable cytotoxicity,
with an IC₅₀ value of 34.5 ± 2.1 µM, outperforming
cisplatin. The superior activity of 2 can be attributed to
its highly oxidized seco-limonoid framework,
characterized by A and B ring cleavage and extensive
ester substitutions. These structural features play a
crucial role in enhancing cytotoxicity. Notably,
amotsangin A is reported here for the first time from
the genus Dysoxylum, specifically from D. parasiticum,
adding a novel member to the chemical profile of this
genus. In contrast, compounds 1 and 3 exhibited no
significant activity (IC₅₀ >100 µM), highlighting the
importance of specific oxidation patterns and ring
modifications in determining anticancer efficacy.
CONCLUSIONS
In this phytochemical investigation, we present the
isolation and characterization of three known
compounds derived from the stem barks of Dysoxylum
parasiticium,
specifically
cneorin-NP36
(1),
amotsangin A (2), and 22(E)-ergosta-6,22-dien3β,5α,8α-triol (3). Compound 1 is identified as a
triterpenoid characterized by a tirucallane-type
backbone, notable for its paired double bond system
located at C-7/C-8. It is differentiated from its
stereoisomer, the euphane-type, by the β-orientation
of the CH3-21 group at C-20. Compound 2 is
classified within the seco-limonoid category,
specifically of the preurianin type, exhibiting significant
modifications to its fundamental structure, including
the presence of an α,β-unsaturated-ε-caprolactone
moiety in ring A and an opening in the B-ring. The
extensive oxidation observed in compound 2 is
reflected not only in its primary skeleton but also in the
presence of two ester substituents at C-11 and C-12.
Additionally, compound 3 is characterized by the
presence of polyhydroxy groups typical of an
ergostane-type steroid at positions C-3, C-5, and C8. The biological efficacy of three identified
compounds (1-3) demonstrated that the modified
limonoid in compound 2 exhibits superior inhibitory
effects on the growth of the human breast cancer cell
line MCF-7 compared to the established
chemotherapeutic agent cisplatin (IC50, 53.0 μM), with
an IC50 value of 34.5 μM for the modified limonoid.
According to Naini et al. (2024b), preurianin-type
limonoids from D. parasiticum, such as paraxylines A–

G, showed notable cytotoxic activity against MCF-7
and HeLa cancer cell lines, which was strongly
associated with their high oxygenation levels and
distinct ring modifications. In line with these findings,
amotsangin A (2) also a highly oxygenated preurianintype limonoid demonstrated potent cytotoxicity against
MCF-7 cells.
ACKNOWLEDGEMENTS
This investigation was funded by Jambi University
Under the Internal Grant, 2024 (HR)
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