Aramatosides C and D,2 Previously Undescribed Triterpene Glycosides Isolated From the Roots of Aralia armata

Abstract

The 2 new oleanane-type triterpene glycosides, 23-hydroxyoleanolic acid-[28-O-β-D-glucopyranosyl]-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside}, (1) and oleanolic acid-[28-O-β-D-glucopyranosyl]-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside} (2) were isolated from the roots of Aralia armata. Their chemical structures were elucidated by using a combination of high resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1 dimensional (1D), and 2 dimensional (2D) nuclear magnetic resonance spectral data, as well as by comparison with the previous literature. Compounds 1 and 2 displayed weak cytotoxic activity toward KB and HepG2 cell lines with IC₅₀ values of 25.1 ± 1.2 and 23.7 ± 0.9 µM (for 1) and 29.5 ± 1.3 and 23.9 ± 0.7 µM (for 2), respectively, compared to that of the positive control compound, ellipticine (IC₅₀: 1.3 ± 0.1 and 1.6 ± 0.1 µM, respectively) in in vitro assay.

Keywords

Araliaceae aramatoside C aramatoside D triterpene glycoside cytotoxic activity

Introduction

Aralia armata (Wall.) Seem. (Araliaceae) is a common herbal in Vietnam that has been used in traditional medicine to cure hepatitis, arthritis, stomachache, malaria, and snake rolling.¹ Phytochemical study of A armata led to the isolation of oleanane-type triterpene glycosides as the main components of the leaves² and roots.³ From the leaves of this plant growing in Vietnam, 14 oleanane-type triterpene glycosides have been isolated and some of them exhibited cytotoxic activity against some cancer cell lines.^4-6 However, no chemical and bioactive studies have been made on the roots of Vietnamese A armata. Continuing our search for bioactive compounds from A armata, herein, we report the isolation and structural elucidation of 2 previously undescribed oleanane-type triterpene saponins (named as armatosides C and D) from the roots of this plant. The cytotoxic activity of these compounds on some cell lines was also evaluated.

Results and Discussion

Compound 1 was obtained as white amorphous powder from the methanol extract of the roots of A armata. The molecular formula of 1 was determined to be C₅₄H₈₈O₂₄ by its HR-ESI-MS results ( m/z 1155.5341 [M + ³⁵Cl]⁻ [calcd. for C₅₄H₈₈O₂₄³⁵Cl: 1155.5354, Δ = −1.1 ppm], m/z 1157.5289 [M + ³⁷Cl]⁻ [calcd. for C₅₄H₈₆O₂₄³⁷Cl: 1157.5325, Δ = −3.1 ppm]) (Supplemental Figure S1), indicating 11°of unsaturation. Analyzing the ¹H nuclear magnetic resonance (NMR) and ¹³C NMR spectra, combined with the heteronuclear single quantum coherence spectroscopy (HSQC) spectrum of 1 showed 6 methyl groups (δ_H 0.76/δ_C 13.2, δ_H 1.00/δ_C 16.4, δ_H 0.83/δ_C 18.7, δ_H 1.19/δ_C 26.4, δ_H 0.95/δ_C 24.0, and δ_H 0.93/δ_C 33.5), 1–CH = C < double bond (δ_H 5.27 [t, J = 3.5 Hz]/δ_C 123.8 and δ_C 144.9), 1 carbonyl group (δ_C 178.1), 1 C-3 methine carbinol group (δ_H 3.67 [dd, J = 13.5, 5.4 Hz]/δ_C 84.9), and 4 sugar moieties identified from the anomeric signals at δ_H 5.40 (d, J = 8.0 Hz)/δ_C 95.7, δ_H 4.53 (d, J = 7.5 Hz)/δ_C 104.8, δ_H 4.89 (d, J = 7.5 Hz)/δ_C 103.5, and δ_H 4.63 (d, J = 7.5 Hz)/δ_C 105.3 (Supplemental Figures S2 to S11). The above data suggested that compound 1 was an oleanane-type triterpene glycoside, a very typical substance class of Aralia species.^3,6,7 Comparing the NMR data of the aglycone of 1 with the corresponding data of the oleanane-type saponins araliasaponins XII to XVIII found that the methyl at C-23 of these compound was replaced by an oxygenated methylene group (CH₂-OH) in 1, which was confirmed by the additional signals at δ_H 3.78 and 3.28 (each, 1H, d, J = 11.0 Hz)/δ_C 64.8, as well as by the absence of CH₃-23 signals in the NMR spectra of 1. Furthermore, the heteronuclear multiple bond correlation (HMBC) correlations from H-24 (δ_H 0.76) to carbons C-23 (δ_C 64.8)/C-3 (δ_C 84.9)/C-4 (δ_C 44.2)/C-5 (δ_C 48.0), and from H-23 (δ_H 3.28 and 3.78) to C-24 (δ_C 13.2)/C-3/C-4/C-5 definitely indicated that the hydroxyl group was at C-23 and the methine carbinol carbon was at C-3. The double bond was determined at C-12/C-13, suggested from the similar biogenetic oleanane-type saponins from Aralia species,^3,6,7 and further confirmed by the observations of the HMBC correlations from H₃-26 (δ_H 1.19) to C-13 (δ_C 144.9) and from H-18 (δ_H 2.87) to C-12 (δ_C 123.8)/C-13. In the NOESY spectrum, H-3 (δ_H 3.67) had cross peaks to H-23 (δ_H 3.28/3/78) and H-5 (δ_H 1.23), and H-5 had a cross peak to H-23 (Supplemental Figure S15). This evidence, together with the larger coupling constant of H-2 and H-3 (J = 13.5 Hz), indicated that H-3 (axial), H-23, and H-5 had α-orientation. A set of carbon signals at δ_C 95.7, 74.0, 78.3, 71.2, 78.7, and 62.5, which had corresponding HSQC cross peaks with protons H-1′ (δ_H 5.40), H-2′ (δ_H 3.33), H-3′ (δ_H 3.42), H-4′ (δ_H 3.35), H-5′ (δ_H 3.37), and H-6′ (δ_H 3.70/3.84), the ¹H-¹H COSY cross peaks of H-1′/H-2′/H-3′/ H-4′/H-5′/H-6′, and the HMBC correlation from H-1′ to C-28 (δ_C 95.7) indicated that 1 glucopyranosyl sugar was attached to C-28 by an ester linkage. The remaining 18 carbons were assigned to 3 hexose units. Of these, the galactopyranosyl sugar was identified by a set of signals at δ_C 104.8/δ_H 4.53, δ_C 76.6/δ_H 3.98, 85.4/δ_H 3.82, δ_C 70.0/δ_H 4.14, δ_C 76.0/δ_H 3.56, δ_C 63.5/δ_H 3.57 and 3.83, indicated from the HSQC spectrum, as well as by the appearance of H-4′′ as a broad doublet with small coupling constants (J = 3.0 Hz). The galactose unit was attached to C-3, which was confirmed by the HMBC correlation from H-1′′ (δ_H 4.53) to C-3 (δ_C 84.9), from H-3 (δ_H 3.67) to gal C-1′′ (δ_C 104.8), as well as from the NOESY observation between gal H-1′′ (δ_H 4.53) and H-3 (δ_H 3.67).^3,7 Interestingly, the galactose moiety attached directly to C-3 of the aglycone has not been previously found in the Aralia genus. The deshielding of protons H-2′′ (3.98, dd, J = 9.0, 7.5 Hz) and H-3′′ (3.82, dd, J = 9.0, 9.0 Hz), and carbons C-2′′ (δ_C 76.6), and C-3′′ (δ_C 85.4) of this galactose suggested the substitutions at these positions. The 2 remaining glucose sugars were identified by their NMR data, as shown in Table 1, in comparison with the data previously reported^3,7 and further determined from HSQC, HMBC, and ¹H-¹H COSY spectra (Supplemental Figures S11 to S14). The HMBC correlations from glc H-1′′′ (δ_H 4.89) to gal C-2′′ (δ_C 76.6) and from H-1′′′′ (δ_H 4.63) to gal C-3′′ (δ_C 85.4) confirmed that these 2 sugars were attached to C-2′′ and C-3′′ of the galactose. The glycoside linkages were determined to be in the β-form by their larger coupling constant values of the anomeric protons (J = 7.5-8.0 Hz). Later, acid hydrolysis of 1 obtained D-galactose and D-glucose, identified by thin layer chromatography (TLC) comparison with authentic samples, and from the positive sign of optical rotation (see experimental).⁸ Consequently, the structure of 1 was completely established as 23-hydroxyoleanolic acid-[28-O-β-D-glucopyranosyl]-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside}, a new compound named aramatoside C⁶ (Figure 1).

Figure 1.

Chemical structures of compounds 1 and 2.

Table 1.

NMR Spectroscopic Data for the Sugar Moieties of 1 and 2 in Deuterated Methanol.

Pos.		1		2
Pos.		^aδ_C	^bδ_H (mult., J in Hz)	^aδ_C	^bδ_H (mult., J in Hz)
28-O-glc	1′	95.7	5.40 (d, 8.0)	95.7	5.40 (d, 8.0)
	2′	74.0	3.33 (dd, 8.0, 9.0)	74.0	3.33 (dd, 8.0, 9.0)
	3′	78.3	3.42 (t, 9.0, 9.0)	78.4	3.43 (t, 9.0, 9.0)
	4′	71.2	3.35 (t, 9.0, 9.0)	71.2	3.30 (t, 9.0, 9.0)
	5′	78.7	3.37 (m)	78.7	3.38 (m)
	6′	62.5	3.70 (m)/3.84 (m)	62.4	3.70 (m)/3.84 (m)
3-O-gal	1′′	104.8	4.53 (d, 7.5)	105.9	4.42 (d, 7.5)
	2′′	76.6	3.98 (t, 9.0, 7.5)	77.5	3.89 (dd, 9.0, 7.5)
	3′′	85.4	3.82 (t, 9.0, 3.0)	85.4	3.78 (dd, 9.0, 3.0)
	4′′	70.0	4.14 (br d, 3.0)	70.0	4.13 (br d, 3.0)
	5′′	76.0	3.56 (m)	75.7	3.53 (m)
	6′′	63.5	3.57 (m)/3.83 (m)	62.5	3.72 (m)/3.84 (m)
2′′-O-glc	1′′′	103.5	4.89 (d, 7.5)	104.7	4.74 (d, 7.5)
	2′′′	76.0	3.15 (dd, 9.0, 7.5)	76.1	3.14 (dd, 9.0, 7.5)
	3′′′	78.2	3.31 (t, 9.0, 9.0)	78.3	3.30 (t, 9.0, 9.0)
	4′′′	72.3	3.13 (t, 9.0, 9.0)	71.5	3.42 (t, 9.0, 9.0)
	5′′′	78.2	3.35 (m)	78.2	3.35 (m)
	6′′′	62.4	3.70 (m)/3.74 (m)	62.3	3.70 (m)/3.79 (m)
3′′-O-glc	1′′′′	105.3	4.63 (d, 7.5)	105.3	4.62 (d, 7.5)
	2′′′′	75.3	3.32 (dd, 9.0, 7.5)	75.3	3.31 (dd, 9.0, 7.5)
	3′′′′	78.3	3.30 (t, 9.0, 9.0)	78.3	3.30 (t, 9.0, 9.0)
	4′′′′	71.2	3.34 (t, 9.0, 9.0)	71.2	3.34 (t, 9.0, 9.0)
	5′′′′	78.0	3.36 (m)	77.9	3.36 (m)
	6′′′′	62.4	3.70 (m)/3.84 (m)	62.4	3.70 (m)/3.84 (m)

Measured at 100 MHz.

Measured at 400 MHz.

Abbreviation: NMR, nuclear magnetic resonance.

Compound 2 was also obtained as white amorphous powder and its molecular formula was determined to be C₅₄H₈₈O₂₄ from the HR-ESI-MS results (m/z 1139.5402 [M + ³⁵Cl]⁻ [calcd. for C₅₄H₈₈O₂₃³⁵Cl: 1139.5405, Δ = −0.2 ppm], m/z 1141.5414 [M + ³⁷Cl]⁻ [calcd. for C₅₄H₈₈O₂₃³⁷Cl: 1141.5375, Δ = + 3.4 ppm]) (Supplemental Figure S16), indicating 11° of unsaturation. The NMR spectra of 2 were very similar to the corresponding 1s of 1 except for the difference that the 23-CH₂OH signals in 1 were replaced by methyl signals in 2 suggesting that the aglycone of 2 was oleanolic acid and the sugar moieties were the same as in 1. A detailed comparison of their NMR data (Tables 1 and 2) found that the above substitution led to some chemical shift changes at C-3, C-4, and C-5, the same as previously reported.⁹ In addition, 7 methyl groups (δ_C/δ_H: 16.0/0.98, 16.6/0.86, 17.8/0.82, 24.0/0.95, 26.3/1.17, 28.3/1.08, 33.5/0.93), the C-12/C-13 double bond (δ_C/δ_H: 123.9/5.27 and δ_C 144.8), the carboxylate group (δ_C 178.1), the methine carbinol group at C-3 (δ_C 91.5/δ_H 3.14 [dd, J = 13.5, 5.0 Hz]), and the 4 sugar moieties (anomeric signals as δ_C/δ_H: 95.7/5.40 [d, J = 7.5 Hz], 105.9/4.42 [d, J = 8.0 Hz], 104.7/4.74 [d, J = 7.5 Hz], 105.3/4.62 [d, J = 7.5 Hz]) were identified in the NMR spectra of 2 (Supplemental Figures S17 to S31). A larger coupling constant of H-3 and H _ax -2 (J = 13.5 Hz) and a NOESY cross peak between H-3 (δ_H 3.14) and H-5 (δ_H 0.77) was observed indicating that the H-3 orientation was α/axial (Supplemental Figure S31). The lower field signal of the anomeric carbon C-1′ (δ_C 95.7), the higher field signal of the anomeric proton H-1′ (δ_H 5.40), as well as the HMBC correlation from H-1′ to C-28 (δ_C 178.1) confirmed that 1 sugar was attached to C-28 by an ester linkage. The remaining sugar moieties of 2 were identified as glucopyranosyl-(1→2)-[glucopyranosyl-(1→3)]-galactopyranoside, the same as in 1, by the good match in their NMR data (Table 1), and further confirmed by HSQC, HMBC, and ¹H-¹H COSY spectra (Figure 2). The HMBC correlations from gal H-1′′ (δ_H 4.42) to C-3 (δ_C 91.5), from glc H-1′′′ (δ_H 4.74) to gal C-2′′ (δ_C 77.5), and from H-1′′′′ (δ_H 4.62) to gal C-3′′ (δ_C 85.4) indicated that the 2 glucose sugars were attached to C-2′′ and C-3′′ of the galactose and the galactose attached to C-3. Furthermore, the coupling constants (J = 7.5-8.0 Hz) observed for the anomeric protons in the ¹H NMR spectrum of 2 indicated the β-form of all sugar linkages. In addition, acid hydrolysis of 2 obtained D-galactose and D-glucose, identified by TLC comparison with authentic samples and from the positive sign of optical rotation.⁸ Consequently, the structure of 2 was completely established to be oleanolic acid-[28-O-β-D-glucopyranosyl]-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside}, a previously undescribed compound, and named aramatoside D.⁶

Figure 2.

The ¹H-¹H COSY and key heteronuclear multiple bond correlation (HMBC) correlations of compounds 1 and 2.

Table 2.

NMR Spectroscopic Data for the Aglycone Moieties of 1 and 2 in Deuterated Methanol.

Pos.	1		2
Pos.	^aδ_C	^bδ_H (mult., J in Hz)	^aδ_C	^bδ_H (mult., J in Hz)
1	39.6	0.99 (), 1.65 ()	39.9	0.99 (), 1.63 ()
2	26.5	1.80 (), 1.98 ()	27.1	1.72 (), 1.96 ()
3	84.9	3.67 (dd, 13.5, 5.4)	91.5	3.14 (dd, 13.5, 5.0)
4	44.2	–	40.4	–
5	48.0	1.23 (d, 11.0)	57.2	0.77 (d, 11.0)
6	18.9	1.38 (m), 1.50 (m)	19.4	1.41 (m), 1.55 (m)
7	33.4	1.33 (*), 1.50 (m)	34.0	1.33 (*), 1.50 (m)
8	40.7	–	40.8	–
9	49.1	1.65 (m)	49.0	1.59 (m)
10	37.7	–	37.9	–
11	24.6	1.92 (m), 1.94 (m)	24.6	1.89 (m), 1.92 (m)
12	123.8	5.27 (t, 3,5)	123.9	5.27 (t, 3,5)
13	144.9	–	144.8	–
14	43.0	–	42.9	–
15	28.9	1.12 (m), 1.81 (m)	28.9	1.10 (m), 1.81 (m)
16	24.0	1.72 (m), 2.08 (m)	24.0	1.73 (m), 2.06 (m)
17	48.5	–	48.5	–
18	42.6	2.87 (dd, 13.5, 3.5)	42.6	2.87 (dd, 13.5, 3.5)
19	47.2	1.17 (m), 1.74 (m)	47.3	1.18 (m), 1.74 (m)
20	31.5	–	31.5	–
21	34.9	1.23 (), 1.40 ()	34.9	1.23 (), 1.42 ()
22	33.2	1.62 (*), 1.76 (m)	33.2	1.63 (*), 1.75 (m)
23	64.8	3.78 (d, 12.0) 3.28 (d, 12.0)	28.3	1.08 (s)
24	13.2	0.76 (s)	16.6	0.86 (s)
25	16.4	1.00 (s)	16.0	0.98 (s)
26	17.8	0.83 (s)	17.8	0.82 (s)
27	26.4	1.19 (s)	26.3	1.17 (s)
28	178.1	–	178.1	–
29	33.5	0.93 (s)	33.5	0.93 (s)
30	24.0	0.95 (s)	24.0	0.95 (s)

Note: Asterisk indicates overlapped signals.

Measured at 100 MHz.

Measured at 500 MHz.

Abbreviation: NMR, nuclear magnetic resonance.

Compounds 1 and 2 were evaluated in vitro for their cytotoxic activity by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay against 2 human cancer cell lines (KB and HepG2) acquired from the American Type Culture Collection. Compounds 1 and 2 displayed a weak cytotoxic activity toward KB and HepG2 cell lines with IC₅₀ values of 25.1 ± 1.2 and 23.7 ± 0.9 µM (for 1) and 29.5 ± 1.3 and 23.9 ± 0.7 µM (for 2), respectively, compared to that of positive control compound, ellipticine (IC₅₀: 1.3 ± 0.1 and 1.6 ± 0.1 µM, respectively) in in vitro assay (Table 3).

Table 3.

The Cytotoxic Effects of Compounds 1 and 2 Towards KB and HepG2 Cell Lines.

Compounds	IC₅₀ (µM) KB	IC₅₀ (µM) HepG2
1	25.1 ± 1.2	23.7 ± 0.9
2	29.5 ± 1.3	23.9 ± 0.7
Ellipticine^a	1.3 ± 0.1	1.6 ± 0.1

Positive control compound.

Experimental

General

HR-ESI-MS was carried out on an Agilent 6530 Accurate Mass Q-TOF LC/MS. The QTOF instrument was set at 2 GHz in extended dynamic range resolution mode, a negative ESI capillary voltage of 3500 V, fragment or voltage of 175 V, MS scan range of m/z 100 to 1700, and MS acquisition rate of 1.0 spectra per second. The NMR spectra were recorded on a Bruker 500 MHz spectrometer and optical rotation on a Jasco P2000 polarimeter. Column chromatography was performed using silica gel, reverse phase C-18, and diaion HP-20 resins as stationary phase. HPLC was carried out using an AGILENT 1100 HPLC system. For thin layer chromatography, precoated silica gel 60 F₂₅₄ and RP-18 F_254S plates were used. The compounds were visualized by spraying with a solution of H₂SO₄ 5% in ethanol, followed by heating with a heat gun.

Plant Material

A armata roots were collected in Danang province, Vietnam in January 2021. The plant was identified by Dr Nguyen The Cuong at the Institute of Ecology and Biological Resources, VAST. A voucher specimen (coded: NCCT-P71R) was deposited at the Institute of Marine Biochemistry, VAST.

Extraction and Isolation

The dried roots of A armata (5.0 kg) were cut into small species, powdered and then ultrasonically extracted with MeOH, 3 times (each 12 L of MeOH for 60 min). After filtration, the solvent was removed in vacuo to give 135 g of methanol extract. This was suspended in water and successively partitioned with dichloromethane and ethyl acetate (EtOAc) to give organic soluble fractions and a water layer. The water layer was chromatographed on a diaion (HP-20) column washing with water to remove salts and oligosaccharides. Saponins were stepwise eluted by methanol/water (25%, 50%, 75%, and 100% volume of methanol) to give 4 fractions AA1-AA4. Fraction AA2 (12.0 g) was chromatographed on a silica gel column, eluting with dichloromethane/methanol (1/0-0/1, v/v) to give 4 fractions AA2A-AA2D. Fraction AA2C (3.0 g) was chromatographed on a reverse phase C18 column, eluting with methanol/water (3/5, v/v) to give 4 fractions AA2C1-AA2C4. Fraction AA2C2 was further chromatographed by HPLC (J'sphere H-80 column, 250 mm length × 20 mm ID), eluting with 16% acetonitrile in water, with a flow rate of 2 mL/min to give compounds 1 (9.7 mg) and 2 (11.3 mg).

23-Hydroxyoleanolic Acid-[28-O-β-D-Glucopyranosyl]- 3-O-{β-D-Glucopyranosyl-(1→2)-[β-D-Glucopyranosyl-(1→3)]-β-D-Galactopyranoside} (Aramatoside C, 1)

White amorphous powder,

[α]_{D}^{25}

: + 51.0 (c 0.1, MeOH); HR-ESI-MS m/z 1155.5341 [M + ³⁵Cl]⁻ (calcd. for C₅₄H₈₈O₂₄³⁵Cl: 1155.5354, Δ = −1.1 ppm), m/z 1157.5289 [M + ³⁷Cl]⁻ (calcd. for C₅₄H₈₆O₂₄³⁷Cl: 1157.5325, Δ = −3.1 ppm); ¹H NMR (CD₃OD, 500 MHz) and ¹³C NMR (CD₃OD, 125 MHz) data, see Tables 1 and 2.

Oleanolic Acid-[28-O-β-D-Glucopyranosyl]-3-O-{β-D-Glucopyranosyl-(1→2)-[β-D-Glucopyranosyl-(1→3)]-β-D-Galactopyranoside} (Aramatoside D, 2)

White amorphous powder,

[α]_{D}^{25}

: + 45.0 (c 0.1, MeOH); HR-ESI-MS m/z 1139.5402 [M + ³⁵Cl]⁻ (calcd. for C₅₄H₈₈O₂₃³⁵Cl: 1139.5405, Δ = −0.2 ppm), m/z 1141.5414 [M + ³⁷Cl]⁻ (calcd. for C₅₄H₈₈O₂₃³⁷Cl: 1141.5375, Δ = + 3.4 ppm); ¹H NMR (CD₃OD, 500 MHz) and ¹³C NMR (CD₃OD, 125 MHz) data, see Tables 1 and 2.

Acid Hydrolysis of Compounds 1 and 2

Compounds 1 and 2 (each, 8.0 mg) were dissolved in 0.5 mL of 6 N HCL and heated at 60 °C for 1.5 h. After cooling, the mixtures were extracted with EtOAc. The acid aqueous layer was neutralized with 1 N NaOH and freeze-dried. The 2 sugars were identified as glucose and galactose by comparison with authentic samples by TLC using MeCOEt–isoPrOH–Me₂CO–H₂O (20:10:7:6). After preparative TLC of the sugar mixture (for each 1 and 2, 3.3 mg) using this solvent, each isolated sugar was filtered to eliminate SiOH residue. The optical rotation of each purified sugar was measured to afford glucose and galactose as + 19.1 (c 0.1, H₂O) and + 46.2 (c 0.08, H₂O), respectively. By comparing the optical rotations with D-glucose

[α]_{D}^{25}

: + 18.0 (c 0.1, H₂O) and D-galactose

[α]_{D}^{25}

: + 45.0 (c 0.08, H₂O), the glucose and galactose in compounds 1 and 2 were determined to have D-configurations.

Cytotoxic Assay

The cytotoxic assays are the same as described in our previous work^5,6 (see Supplemental Material).

Conclusions

The 2 previously undescribed oleanane-type triterpene glycosides, oleanolic acid-[28-O-β-D-glucopyranosyl]-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside} (1) and 23-hydroxyoleanolic acid-[28-O-β-D-glucopyranosyl]-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-galactopyranoside} (2) were isolated from the roots of A armata. Their chemical structures were elucidated by using a combination of HR-ESI-MS, 1D NMR (¹H, ¹³C NMR) and 2D NMR (HSQC, HMBC, ¹H-¹H COSY, NOESY) spectral data, as well as by comparison with the previous literature. Compounds 1 and 2 displayed moderate cytotoxic activity towards KB and HepG2 cell lines with IC₅₀ values ranging from 23.7 ± 0.9 to 29.5 ± 1.3 µM, compared to that of the positive control compound, ellipticine (IC₅₀: 1.3 ± 0.1 and 1.6 ± 0.1 µM, respectively) in in vitro assay.

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by the Funds for Science and Technology of the University of Danang, University of Science and Education (grant number T2020-TĐ-01) and Vingroup Joint Stock Company and supported by the Domestic Master/ PhD Scholarship Programme of Vingroup Innovation Foundation (VINIF), Vingroup Big Data Institute (VINBIGDATA) for Nguyen Thi Hong Chuong (grant number: VINIF.2020.TS.55).

ORCID iD

Phan V. Kiem

Supplemental Material

Supplemental material for this article is available online.

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