Molekul.
Vol.
No.
July 2024: 242 Ae 249 Articles MOLEKUL eISSN: 2503-0310 https://doi.
org/10.
20884/1.
Sesquiterpenoids from The Stem Bark of Aglaia cucullata (Meliacea.
and Their Cytotoxic Activity Against A549 Lung Cancer Cell Lines Iqbal Wahyu Mustaqim1.
Desi Harneti1*.
Al Arofatus Naini3.
Erina Hilmayanti1.
Darwati1.
Nurlelasari1.
Tri Mayanti1.
Rani Maharani1.
Kindi Farabi1,2.
Ace Tatang Hidayat1,2.
Unang Supratman1,2.
Sofa Fajriah3.
Mohamad Nurul Azmi4.
Yoshihito Shiono5 Department of Chemistry.
Faculty of Mathematics and Natural Sciences.
Universitas Padjadjaran.
Jatinangor 45363.
Indonesia Central Laboratory.
Universitas Padjadjaran.
Jatinangor 45363.
Indonesia Research Center for Raw Materials for Medicine and Traditional Medicine.
National Research and Innovation Agency (BRIN).
Tangerang Selatan.
Banten 15314.
Indonesia School of Chemical Sciences.
Universiti Sains Malaysia, 11800 Minden.
Penang.
Malaysia Department of Food.
Life, and Environmental Science.
Faculty of Agriculture.
Yamagata University.
Tsuruoka.
Yamagata 997-8555.
Japan *Corresponding author email: desi.
harneti@unpad.
Received September 25, 2023.
Accepted February 01, 2024.
Available online July 20, 2024 ABSTRACT.
Sesquiterpenoids are a class of terpenoid compounds with a remarkable diversity of structures and biological Sesquiterpenoids are primarily found in higher plants, such as the Meliaceae family's Aglaia genus.
Aglaia cucullata is a species of Aglaia that is still rarely explored and can potentially contain sesquiterpenoid compounds with cytotoxic activity.
Hence, the research intended to isolate sesquiterpenoids from the n-hexane extract of A.
cucullata stem bark and evaluate their cytotoxic effect against A549 lung cancer cells.
Compounds 1 and 2 were isolated and purified from n-hexane extracts utilizing various chromatographic techniques.
The structure of compounds 1 and 2 was determined by analyzing various spectroscopic methods (IR.
MS, and NMR) and comparing them to previously reported spectral data.
Compound 1 was identified as an isodaucane-type sesquiterpenoid, 10-hydroxy-6,10-epoxy-7.
-isodaucane, and was first reported in Meliaceae family.
Compound 2 was confirmed as an eudesmane-type sesquiterpenoid, eudesm-4.
-ene-1,6-dihydroxy, and was first reported in Aglaia cucullata.
Cytotoxic activity of 1 and 2 were investigated in vitro against A549 lung cancer cells using the PrestoBlue assay and resulted in inactive and low cytotoxicity with IC50 values of 292.
77 and 90.
55 M, respectively.
Key words: Aglaia cucullata, .
A549 cell lines, cytotoxic activity.
Meliaceae, sesquiterpenoids.
INTRODUCTION
Sesquiterpenoids are the most abundant group of plant secondary metabolites, consisting of 15 carbon atoms (C15H.
with over 300 different skeletons (AbuIzneid et al.
, 2020.
Hussain et al.
, 2019.
Liu et al.
More than 7000 sesquiterpenoid compounds have been successfully isolated, primarily as volatile plant oils (Mai et al.
, 2.
Sesquiterpenoids are produced by the mevalonate pathway, which comprises three isoprene units and takes place in the endoplasmic reticulum and through farnesyl pyrophosphate (FPP) (Abbas et al.
Chadwick et , 2.
Sesquiterpenoids can be categorized as acyclic, monocyclic, bicyclic, tricyclic, or tetracyclic, depending on how many carbon rings they contain in their chemical structure (Mai et al.
, 2.
They can also be divided into groups based on the number of carbons are present in the rings.
most rings contain five, six, seven, or even up to eleven carbon atoms (Li et al.
, 2.
The largest genus in the Meliaceae family.
Aglaia, has been reported to contain a large variety of sesquiterpenoid (Harneti et al.
, 2022.
Izdihar et al.
Saeidnia et al.
, 2.
More than 150 different species of Aglaia exist, with 65 of them only being grown in Indonesia (Harneti & Supratman 2021.
Huang et al.
, 2.
The Aglaia spread in tropical and subtropical regions such as Sri Lanka.
India.
Southern China.
Southeast Asia.
Northern Australia, and the Pacific Islands (Hutagaol et al.
, 2021.
Pannell et al.
Yodsaoue et al.
, 2012.
Farabi et al.
, 2022.
Kavitha et al.
, 2022.
Xia et al.
, 2.
In Indonesia, the Sumatera.
Kalimantan.
Jawa.
Sulawesi.
Bali.
Flores, and Papua are home to the Aglaia genus (Pannell et al.
, 2.
The bark of Aglaia has historically been used as a traditional Indonesian Sesquiterpenoids from The Stem Bark Iqbal Wahyu Mustaqim, et al.
herbal remedy to treat fever, influenza, cough, and other skin issues (Milawati et al.
, 2019.
Sianturi et al.
Since 1965, hundreds of compounds have been successively isolated and elucidated from many species of Aglaia genus, including determining its biological activity (Harneti & Supratman, 2.
Besides the content of sesquiterpenoids.
Aglaia genus also contains various biologically active secondary metabolites, such as diterpenoids, triterpenoids, limonoids, steroids, flavaglines, bisamides, and lignans (Harneti & Supratman, 2021.
Yan et al.
Those compounds showed biological activity including, cytotoxic, insecticidal, anti-inflammataory, antifungal, and molluscicide, and cytotoxic as the most The previous research on Aglaia species makes this plant an interesting object to explore for the discovery of new biologically active compounds including cytotoxic ones (Harneti & Supratman, 2.
Aglaia cucullata is a unique species in Aglaia genus grown in mangrove environment.
Previously, this plant was known as Amoora cucullata.
This species is observed in lowland and tidal riverbanks native to Southeast Asia.
In Indonesia this plant can be found in Kalimantan Island.
cucullata is a tree species associated with mangrove plant (Meepol et al.
Since A.
cucullata remains unexplored yet, this species together with its unique association and environments is expected to produce remarkable secondary metabolites especially for cytotoxic Previous phytochemical investigation revealed that cucullata, contains many potential secondary diterpenoids, and triterpenoid with cytotoxic activities against several cancer cell lines such as oral human KB, human breast cancer BC, and small cell lung NCIH187 from the fruits, leaves, and roots (Harneti et al.
On the other hand, the human A549 lung cancer cell showed high recistancy against cisplatin as a cancer drug (Harneti & Supratman 2.
Therefore, those findings inspired us to explore the sesquiterpenoid compounds from A.
cucullata and their cytotoxic acitvity against human lung cancer A549 cell.
In this study we report here the isolation, structure elucidation of sesquiterpenoids 1 and 2 from the stembark A.
cucullata and cytotoxic activity against A549 lung cancer cell lines.
Various chromatography techniques were applied including vacuum liquid chromatography (VLC) and open column chromatography.
Structure elucidation of isolated compounds were using spectroscopic techniques including FTIR, mass spectroscopy, 1H, and 13C NMR .
ncluding one and two dimensiona.
Prestoblue assay were used to determine cytotoxic activity of compounds 1 and 2 against A549 lung cancer cell lines.
The isolation and structure elucidation of isolated compounds 1 and 2 were conducted for the first time in this species.
EXPERIMENTAL SECTION
General Experiment Procedure IR spectra were collected in a KBr plate using a PerkinElmer Spectrum 100 FT-IR spectrometer (PerkinElmer.
Shelton.
USA).
Mass spectra were measured using Waters Xevo QTOF mass spectrometer (Waters.
Mildford.
USA).
NMR spectra were retrieved using JEOL JNM-ECX500R/S1 spectrometer (JEOL.
Tokyo.
Japa.
and Bruker Av-500 spectrometer (Bruker.
Karlsruhe.
German.
, both at 500 MHz for 1H and 125 MHz for 13C, with tetramethyl silane (TMS) as an internal standard.
The column chromatography was carried out on ODS RP-18 and silica G60 (Merck, 70-230 mesh and 230-400 mes.
and directed by thin layer chromatography (TLC) analyses with a silica G60 GF254 (Merck, 0.
25 m.
using a variety of solvent systems, and spot detection utilizing 10% H2SO4 in ethanol followed by heating of 100 AC and checked under UV at wavelengths 254 and 365 nm.
Material Acetone, chloroform .
ro-analys.
, ethanol, ethyl acetate, n-butanol, n-hexane, methanol, methylene chloride, and water are solvents used for extraction, fractionation, isolation, and purification with proanalyst and technical quality that has been distilled.
American Type Culture Collection (ATCCA CCL185TM.
Manassas.
Virginia.
USA) provided the A549 Roswell Memorial Park Medium (RPMI) 1640 (Cat.
No.
Gibco.
New York.
USA) was used, along with 10% Fetal Bovine Serum (FBS) (Cat.
No.
Gibc.
and 1% Penicillin-streptomycin (Cat.
No.
Gibc.
The cells were incubated at 37 AC in a 5% CO2 incubator (Cat.
No.
8000DH,
Thermo Fisher Scientific.
Waltham.
Massachusetts.
USA).
Plant Material The stem bark of A.
cucullata was collected in December 2020 from the Manggar River in Balikpapan.
East Kalimantan.
This sample was assessed at the Herbarium Wanariset.
Balikapapan .
ollection No.
FF7.
, and archived at the Faculty of Forestry.
Universitas Mulawarman.
Samarinda.
East Kalimantan.
Indonesia.
Extraction.
Isolation, and Characterization of Secondary Metabolite The air-dried A.
cucullata stem bark powder .
was macerated using ethanol .
L, 7 y 24 .
The ethanol solvent was evaporated with a vacuum rotary evaporator at 40 AC to yield a concentrated ethanol extract residue .
The crude ethanol extract was suspended in a mixture of ethanol:water .
before partitioning with n-hexane, ethyl acetate, and nbutanol.
The crude fraction of n-hexane .
, ethyl acetate .
, and n-butanol .
were obtained through evaporation.
The n-hexane crude vacuum-liquid chromatography (VLC) with silica G60 .
-400 mes.
Molekul.
Vol.
No.
July 2024: 242 Ae 249 as a stationary phase and eluted gradient using nhexane:ethyl acetate .
:0 -0:100, 10% v/.
followed by ethyl acetate:methanol .
:0 0:100, 10% v/.
to yield seven fractions (A-G).
Fraction C .
was further separated using VLC on silica G60 .
-400 mes.
eluted in gradient systems with n-hexane:ethyl acetate .
:0-50:50, 10% v/.
to result four subfractions (C1-C.
Subfraction C2 .
was subjected to silica G60 .
-400 mes.
column chromatography (CC) eluted gradient using n-hexane:ethyl acetate .
:0 80:20, 1% v/.
to obtain four subfractions (C2A-C2D).
Subfraction C2C .
8 m.
was separated by CC over silica G60 .
-400 mes.
and eluted with nhexane:ethyl acetate .
:10, v/.
to afford five subfractions (C2C1-C2C.
Subfraction C2C4 .
was purified further with CC over silica G 60 .
400 mes.
using an isocratic mixture of n-hexane:ethyl acetate .
:15, v/.
to give compound 1.
Subfraction C4 .
was separated by gradient elution of n-hexane:ethyl acetate .
:0 30:70, 2% v/.
on CC silica G60 .
-230 mes.
to yield ten subfractions (C4A-C4J).
Subfraction C4H .
5 m.
was subjected to reverse phase CC on ODS eluted with methanol:water .
:20, v/.
to obtain four subfractions (C4H1-C4H.
Subfraction C4H3 .
6 m.
was subjected to CC silica G60 .
-400 mes.
eluted with an isocratic mixture of nhexane:chloroform:ethyl acetate .
:40:30, v/.
to (C4H3A-C4H3C).
Subfraction C4H3B .
5 m.
was further purified with silica gel CC .
-400 mes.
eluted with an isocratic n-hexane:chloroform:ethyl acetate .
:40:30, v/.
to give compound 2.
10-Hydroxy-6,10-epoxy-7.
-isodaucane .
Ae colorless oil.
IR Imax cm-1: 3406, 2955, 1384, 1367, 1H-NMR (CDCl3, 500 MH.
: H 1.
H, m.
H2.
, 1.
H, m.
H-2.
, 1.
H, m.
H-3.
, 1.
H, m.
H-3.
, 1.
H, s.
H-.
, 1.
H, s.
H-.
, 96 .
H, s.
H-.
, 2.
H, m.
H-8.
, 2.
H, m.
H-8.
, 2.
H, dd.
J = 4.
0,7.
0 Hz.
H-9.
H-9.
, 1.
H, m.
H-.
, 0.
H, d.
J = 6 Hz.
CH3-.
, 0.
H, d.
J = 6.
5 Hz.
CH3-.
, 4.
H-14.
, 4.
H, s.
H-14.
, 1.
H, s.
CH3-.
C-NMR (CDCl3, 125 MH.
Table 1.
HR-TOF-MS,
m/z 237.
1856 [M H ] .
C15H25O2 m/z = eudesm-4.
-ene-1-6-dihydroxy .
Ae colorless IR Imax cm-1: 3406, 2965, 1634, 1376, 1027.
1HNMR (CDCl3, 500 MH.
: H 3.
H, dd.
J = 0,11.
0 Hz.
H-.
, 1.
H, m.
H-2.
, 1.
H, m.
H-2.
, 2.
H, dd.
J = 4.
5,13.
0 Hz.
H-3.
, 2.
H, dd.
J = 4.
5,13.
5 Hz.
H-3.
, 1.
H, d.
J = 9.
Hz.
H-.
, 3.
H, t.
J = 9.
5 Hz.
H-.
, 1.
H, t.
J = 11.
5 Hz.
H-.
, 1.
H, m.
H-8.
, 1.
H, m.
H-8.
, 1.
H, dt.
J = 3.
0,14.
0 Hz.
H-9.
, 1,24 .
H, m.
H-9.
, 2,25 .
H, m.
H-.
, 0.
H, d.
J = 0 Hz.
CH3-.
, 0.
H, d.
J = 6.
5 Hz.
CH3-.
, 67 .
H, s.
CH3-.
, 5.
H, s.
H-15.
, 4.
H-15.
, 2.
H, s, -OH).
13C-NMR (CDCl3, 125 MH.
Table 1.
HR-TOF-MS, m/z 239.
2006 [M H ]
C15H27O2 m/z = 239.
Cytotoxic Assay by PrestoBlue Method The PrestoBlue cell viability method was used to test the cytotoxic activity of compounds in accordance with those previous reports (Naini et al.
, 2023a,.
The A549 lung cancer cells were cultured at a density of 2 y 104 cells per well into 96-well microliter plates for 24 hours at 37 AC in a humidified atmosphere of 5% CO2 in Roswell Memorial Park Institute (RPMI) 1640 medium supplemented with 10% .
Fetal Bovine Serum (FBS) and 1 L/mL The compounds were put into the wells after 24 hours.
Viability was assessed after 96 hours by determining the metabolic conversion reduction of resazurin substrate into pink fluorescent resofurin product produced in viable cells.
The PrestoBlue assay results were read at 570 nm using a multimode All compounds were evaluated at eight 90, 7.
81, 15.
63, 31.
25, 62.
00, 250.
00, and 500.
00 g/mL in 100 % DMSO and with a final concentration of 2 % in each Each compound concentration was evaluated in two parallel experiments, and IC50 values were determined using the linear regression method in Microsoft Excel software.
Figure 1.
Chemical structure of compound 1 and 2 Sesquiterpenoids from The Stem Bark Iqbal Wahyu Mustaqim, et al.
RESULTS AND DISCUSSION
Compound 1 was isolated as a colorless oil that dissolves in chloroform and turns a purple-pinkish in a thin layer chromatography (TLC) plate when sprayed with 10% sulfuric acid in ethanol, representing the presence of a terpenoid structure.
Compound 1 is not fluorescent under UV light at 254 nm and 365 nm Thus there is no conjugated doublebond system.
The molecular formula determined by HR-TOFMS ([M H ]) (Figure S.
was C15H25O2 with m/z 237.
1856, calcd.
m/z 237.
1855, which needed four degrees of unsaturation.
Absorption bands were observed in the IR spectra (Figure S.
at 3406 cm-1 (OH), 2955 cm-1 (C-H sp.
, 1384 cm-1 and 1367 cm1 .
em-dimethy.
, and 1076 cm-1 (C-O).
The 1H-NMR (CDCl3 500 MH.
spectrum (Figure S.
revealed three methyl groups consisting of two secondary methyls at H/ppm 0.
H, d.
J = 6.
5 Hz.
CH3-.
H, d.
J = 6.
0 Hz.
CH3-.
, and one tertiary methyl at H/ppm 1.
H, s.
CH3-.
One olefinic methylene group resonating at H/ppm 4.
H, s.
H-14.
H, s.
H-14.
, as well as one oxymethine group resonating at H/ppm 3.
H, s.
H-.
The 13C-NMR (CDCl3 125 MH.
and DEPT 135 spectra (Figure S.
revealed the existence of 15 carbons (Table .
Assigning of carbon signals by HSQC spectrum (Figure S.
represented three methyls at C/ppm 21.
6 (CH3-.
, 21.
7 (CH3-.
, and 20.
(CH3-.
, four sp3 methylenes at C/ppm 35.
9 (C-.
7 (C-.
, 26.
5 (C-.
, and 33.
2 (C-.
, one sp2 methylenes at C/ppm 108.
5 (C-.
, three methines at C/ppm 57.
7 (C-.
, 58.
9 (C-.
, and 34.
3 (C-.
one oxygenated methine at C/ppm 86.
1 (C-.
, one quarternary sp3 carbon at C/ppm 54.
6 (C-.
, and one quarternary oxygenated carbon at C/ppm 105.
2 (C.
, and one quarternary sp2 carbon at C/ppm 144.
(C-.
Thence, the 1H- and 13C-NMR data implicity show the presence of a sesquiterpenoid bicyclic skeleton with an epoxide ring and olefinic.
The correlations between H2-H3-H4-H5.
H4-H11.
H8-H9.
H11H12, and H11-H13 were observed in the 1H-1H COSY spectrum (Figure S.
indicating the isopropyl group located at C-4.
Furthermore, the HMBC correlations of the methyl protons to their nearby carbons supported the interpretation of proton signals from one tertiary methyl and two secondary methyls.
The correlations of CH3-12 (H/ppm 0.
and CH3-13 (H/ppm 0.
to H/ppm 34.
3 (C-.
(C-.
showed isopropyl group attached to C-4.
Clear correlations between CH3-15 (H/ppm 1.
to C/ppm 35.
9 (C-.
, 54.
6 (C-.
, 58.
9 (C-.
, and 105.
(C-.
confirmed that C-15 attached to C-1 of quarternary carbon.
The correlations of methylene protons at H/ppm 2.
33 (H-.
to C/ppm 86.
(C-.
9 (C-.
, and also at H/ppm 2.
01 (H9.
73 (H-9.
to C/ppm 105.
2 (C-.
and 9 (C-.
indicated the presence of ether bridge at C-6/C-10 and double bond at C-7/C-14.
The oxygenated proton correlations at H/ppm 3.
96 (H.
to C/ppm 105.
2 (C-.
5 (C-.
verified an ether bridge at C-6/C-10 and double bond at C7/C-14 placed adjacent to ether bridge.
The correlations from 10-OH at H/ppm 2.
56 to C/ppm 2 (C-.
, 54.
6 (C-.
, and 105.
2 (C-.
confirmed quarternary oxygenated carbon at C-1 with hydroxyl The key 1H-1H COSY and HMBC correlations further confirmed the planar structure of 1 (Figure .
The NOESY correlations (Figure .
between H-4 (-oriente.
with CH3-15 proposed that CH3-15 was -oriented.
Moreover, the correlations between H-5 (-oriente.
with H-6 and 10-OH advised that both H-6 and 10-OH were -oriented.
When the NMR data from compound 1 were compared to the literature isolated from Bursera graveolens (Yukawa et al.
(Table .
, it was discovered that it is 10-hydroxy-6,10-epoxy-7.
isodaucane, which was isolated for the first time in the Meliaceae family and Aglaia genus.
Figure 2.
Selected 1H-1H COSY and HMBC correlations of compound 1 Molekul.
Vol.
No.
July 2024: 242 Ae 249 Figure 3.
Selected NOESY correlations of compound 1 Table 1.
NMR data for compound 1 10-hidroxy-6,10-epoxy-7.
isodaucane* C .
H (OcH.
H, d, 6.
H, d, 6.
H, br.
H, br.
H, .
Compounds 1* Posisi C .
H (OcH.
H, .
H, .
H, .
H, .
H, .
H, .
H, .
H, .
H, .
H, .
H, dd, 7.
0, 4.
H, .
H, d, .
H, d, 6.
H, .
H, .
H, .
*Assessed in CDCl3 .
MHz for 1H and 125 MHz for 13C) Compound 2 is a colorless oil that is dissoluble in chloroform and change to purple in the TLC plate when sprayed with 10% sulfuric acid in ethanol, indicating the presence of a terpenoid structure.
Compound 2 is not fluorescent under UV light at 254 nm and 365 nm wavelengths, indicating that it lacks a conjugated double bond system.
The HR-TOF-MS spectrum (Figure S.
showed [M H ] m/z 239.
m/z 239.
, which conforms to the molecular formula C15H27O2 and thus necessary three degrees of unsaturation.
The absorption peaks in the IR spectrum (Figure S.
of 3406 cm-1 (OH), 2965 cm-1 (C-H sp.
, 1634 cm-1 (C=C), 1376 cm-1 .
em- dimethy.
, and 1027 cm-1 (C-O).
The 1H-NMR (CDCl3 500 MH.
spectrum (Figure S.
displayed three methyl groups composed of two secondary methyls at H/ppm 0.
H, d.
J = 7.
0 Hz.
CH3-.
H, d.
J = 6.
5 Hz.
CH3-.
, and one tertiary methyl at H/ppm 0.
H, s.
CH3-.
, signifying the eudesmane-type The representation of a characteristic signal for olefinic protons at H/ppm 5.
H, s.
H-15.
and 75 .
H, s.
H-15.
was then demonstrated.
Additionally, the signal for the oxygenated protons was spotted at H/ppm 3.
H, t.
J = 9.
5 Hz.
H-.
and 42 .
H, dd.
J = 5.
0,11.
0 Hz.
H-.
Sesquiterpenoids from The Stem Bark Iqbal Wahyu Mustaqim, et al.
Table 2.
NMR data for compound 2 Position Compound 2* H (OcH.
H, dd, 11.
0, 5.
H, .
H, .
C .
H, dd, 13.
0, 4.
H, dd, 13.
5, 4.
H, d, 9.
H, t, 9.
H, t, 11.
H, .
H, .
H, dt, 14.
0, 3.
H, .
H, .
H, d, 7.
H, d, 6.
H, .
H, .
H, .
-ena-1,6-diol* C .
H (OcH.
H, dd, 11.
6, 4.
H, dtd, 12.
5, 5.
H, qd, 12.
7, 5.
H, d, 13.
1, 5.
H, brtd, 13.
4, 5.
H, brd, 9.
H, t, 10.
H, tt, 12.
5, 3.
H, .
H, qd, 12.
0, 2.
H, dt, 12.
4, 2.
H, td, 13.
1, 3.
H, sed, 7.
0, 2.
H, d, 7.
H, d, 7.
H, .
H, br.
H, br.
*Assessed in CDCl3 .
MHz for 1H and 125 MHz for 13C) C-NMR spectrum with DEPT 135 (Figure S.
detailed analysis showed the presence of fifteen carbons consisting three methyls at C/ppm 21.
(CH3-.
, 16.
3 (CH3-.
, and 11.
6 (CH3-.
, four sp3 methylenes at C/ppm 31.
9 (C-.
, 35.
1 (C-.
, 18.
(C-.
, and 36.
3 (C-.
, one sp2 methylene at C/ppm 8 (C-.
, three methines at C/ppm 55.
9 (C-.
3 (C-.
, and 25.
9 (C-.
, two oxygenated methines at C/ppm 79.
0 (C-.
9 (C-.
, one quarternary sp3 carbon at C/ppm 41.
7 (C-.
, and one quarternary sp2 carbon at C/ppm 146.
2 (C-.
These functionalities are attributed to one of the three degrees of unsaturation.
Two leftover hydrogen deficiency indexes have assigned the bicyclic sesquiterpenoid structure (Milawati et al.
, 2.
Compound 2 is classified as a eudesmane-type sesquiterpenoid structure due to the quantity of methyl and methylene in the 1H-NMR, 13C-NMR, and DEPT 135 spectra (Zhang et al.
, 2.
A comparative of the NMR data of 2 and eudesm-4.
-ene-1-6diol isolated from Litsea verticillata (Zhang et al.
confirmed their structures were very similar (Table .
As an outcome, 2 was described as a eudesm-4.
-ene-1-6-dihydroxy, isolated for the first time in this plant.
The cytotoxicity activity compounds 1 and 2 were tested against the A549 lung cancer cell lines using a method stated previously and doxorubicin .
M) as positive control (Xu et al.
, 2.
Half maximal inhibitory concentration (IC.
was used to show the concentration of a molecule demanded to inhibit a particular biological process by half .
%) (Qureshi et al.
, 2.
Compounds 1 and 2 had IC50 values of 292.
77 M and 90.
55 M, respectively, indicating they were inactive and low (Naini et al.
Compound 1 has never been biologically tested (Da Silva et al.
, 2017.
Yukawa et al.
, 2.
while compound 2 has been tested its cytotoxicity which showed no acitivitiy against HeLa cervical cancer cells and skin melanoma B16-F10 (Harneti et , 2022.
Zhang et al.
, 2.
, so in this study, the first time to conduct a cytotoxic assay on lung cancer cells A549.
CONCLUSIONS
Two types of sesquiterpenoid compounds, 10hydroxy-6,10-epoxy-7.
-isodaucane .
-ene-1-6-diol .
, were isolated from the stem bark of A.
Compound 1 was discovered for the first time in the Meliaceae family and Aglaia genus, while compound 2 was reported for A.
cucullata for the first time.
The cytotoxic activity of compounds 1 and 2 against the A549 lung cancer cell line was assessed, and the IC50 values revealed inactive and low cytotoxicity.
The partial structural modification of the isolated compound allows for further use of it as a lead compound for potential anticancer drug candidates.
Molekul.
Vol.
No.
July 2024: 242 Ae 249
ACKNOWLEDGEMENTS
This study was funded by the Ministry of Education and Culture.
Innovative and Research Council.
Indonesia.
Master Thesis Research (PTM) Grant, (No.
1316/UN6.
1/PT.
00/2.
by Desi Harneti and Academic Leadership Grant (ALG) from Universitas Padjadjaran.
Indonesia (No.
2203/UN6.
1/PT.
by Unang Supratman.
against b16-f10 melanoma skin cancer cell.
Indonesian Journal of Chemistry, 21.
, 1560Ae Li.
Howell.
Fang.
, & Zhang.
Sesquiterpenes in grapes and wines:
Occurrence, biosynthesis, functionality, and REFERENCES