Synthesis and tumor cytotoxicity of novel amide derivatives of β-hederin

Thirteen novel triterpenoid saponins, designed as amide derivatives of the natural cytotoxic saponin β-hederin, were synthesized by a stepwise glycosylation strategy. The in vitro cytotoxic activity of these compounds was evaluated against five different tumor cell lines. Most of the evaluated compounds showed effective inhibitory activity against at least one tumor cell line at micromolar concentrations. The preliminary structure-activity relationships (SAR) indicate that mide derivatization at C-28 resulted in highly cytotoxic derivatives on specific tumor cell lines, and also resulted in an increase in the antitumor selectivity of β-hederin.     

New Triterpenoid Glycosides from the Roots of Camellia oleifera Abel

Five new triterpenoid saponins, oleiferosides I–M ( 1 – 5 , resp.) were isolated from the roots of Camellia oleifera Abel . Their structures were elucidated by a combination of 1D‐ and 2D‐NMR spectroscopy, mass spectrometry, and chemical methods. All the compounds were identified as oleanane‐type saponins with sugar moieties linked to C(3) of the aglycone. In addition, cytotoxic activities of these saponins were evaluated against four human tumor cell lines (A549, B16, BEL‐7402, and MCF‐7) by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) in vitro assay. All of the compounds showed significant cytotoxic activities against the tested cell lines.     

Cytotoxic 13,28 Epoxy Bridged Oleanane-Type Triterpenoid Saponins from the Roots of Ardisia crispa

Ardisiacrispin D–F (1–3), three new 13,28 epoxy bridged oleanane-type triterpenoid saponins, together with four known analogues (4–7) were isolated from the roots of Ardisia crispa. The structures of 1–7 were elucidated based on 1D and 2D-NMR experiments and by comparing their spectroscopic data with values from the published literatures. Ardisiacrispin D–F (1–3) are first examples that the monosaccharide directly linked to aglycone C-3 of triterpenoid saponins in genus Ardisia are non-arabinopyranose. In the present paper, all compounds are evaluated for the cytotoxicity against three cancer cell lines (HeLa, HepG2 and U87 MG) in vitro. The results show that compounds 1, 4 and 6 exhibited significant cytotoxicity against Hela and U87 MG cells with IC₅₀ values in the range of 2.2 ± 0.6 to 9.5 ± 1.8 µM. The present investigation suggests that roots of A. crispa could be a potential source of natural anti-tumor agents and their triterpenoid saponins might be responsible for cytotoxicity.     

Dammarane-Type Triterpenoid from the Stem Bark of Aglaia elliptica (Meliaceae) and Its Cytotoxic Activities

Two new dammarane-type triterpenoid fatty acid ester derivatives, 3β-oleate-20S-hydroxydammar-24-en (1) and 3β-oleate-20S,24S-epoxy-25-hydroxydammarane (2) with a known dammarane-type triterpenoid compound, such as 20S-hydroxydammar-24-en-3-on (3), were isolated from the stem bark of Aglaia elliptica (C.DC.) Blume. The chemical structures were determined by spectroscopic methods, including FTIR, NMR (one and two-dimensional), and HRESITOF-MS analysis, as well as chemical derivatization and comparison with previous literature. Furthermore, the synthetic analog resulting from transesterification of 1 and 2 also obtained 3β,20S-dihydroxy-dammar-24-en (4) and 20S,24S-epoxy-3β,25-dihydroxydammarane (5), respectively. The cytotoxic effect of all isolated and synthetic analog compounds was evaluated using PrestoBlue reagent against MCF-7 breast cancer cell and B16-F10 melanoma cell lines. The 20S-hydroxydammar-24-en-3-on (3) showed the strongest activity against MCF-7 breast cancer and B16-F10 melanoma cell, indicating that the ketone group at C-3 in 3 plays an essential role in the cytotoxicity of dammarane-type triterpenoid. On the other hand, compounds 1 and 2 had very weak cytotoxic activity against the two cell lines, indicating the presence of fatty acid, significantly decreasing cytotoxic activity. This showed the significance of the discovery to investigate the essential structural feature in dammarane-type triterpenoid, specifically for the future development of anticancer drugs.     

Synthesis and structure–activity relationship study of cytotoxic lupane-type 3β-O-monodesmosidic saponins with an extended C-28 side chain

A concise synthesis of lupane triterpenes with an elongated carbon chain at the C-28 position, as well as saponins containing d-mannose, l-arabinose, and l-rhamnose moieties at the C-3 position is described. The overall synthesis of the new triterpenes involved seven linear steps starting from natural betulin: selective protection of a hydroxyl group, oxidation, elongation of the carbon chain by Grignard reaction, and deoxygenation. O-Glycosides were obtained by glycosylation of triterpenes with classical Schmidt's donors. Additionally, all new compounds were evaluated in vitro for their cytotoxic activities. Several triterpenes and the corresponding saponins exhibited an interesting cytotoxic activity profile against human cancer cell lines. The therapeutical index of active triterpenes is very high, since almost none of them were cytotoxic for normal BJ fibroblasts. These results open the way to the synthesis of various lupane-type saponin derivatives as potentially bioactive compounds.     

Two new noroleanane-type triterpenoid saponins from the stems of Stauntonia chinensis

Two new noroleanane-type triterpenoid saponins, 3β,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-β-L-fucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranoside (1) and 3β,20α,24-trihydroxy-29-norolean-12-en-28-oic acid 24-O-β-D-glucopyranosyl-(1→2)-[α-L-arabinopyranosyl-(1→3)]-β-D-glucopyranoside (2) were isolated from the stems of Stauntonia chinensis DC., together with three known compounds, brachyantheraoside B₂ (3), eupteleasaponin Ⅷ (4) and fargoside B (5). Their structures were elucidated by spectroscopic and chemical methods. The cytotoxic activities of compounds 1 and 2 were evaluated against five human tumor cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780). Compounds 1 and 2 showed moderate cytotoxic activities toward the tested cell lines with IC₅₀ values ranging from 12.71 to 32.04 μM.     

Machilusides A and B: structurally unprecedented homocucurbitane glycosides from the stem bark of Machilus yaoshansis

Two structurally novel homocucurbitane triterpenoid glycosides, machilusides A (1) and B (2), possessing an unprecedented C(36) skeleton with a D-fructose moiety incorporated into a cucurbitane nucleus forming unique cage-like tricyclic ring moieties, were isolated from the stem bark of Machilus yaoshansis. Their structures were determined by spectroscopic methods. Both compounds exhibited nonselective cytotoxic activities against several human cancer cell lines. The biosynthetic pathway of 1 and 2 was postulated.     

Intramolecular interchain reactions in bidesmosidic glycosides, a new insight into carbohydrate rearrangements induced by electrospray ionisation

Glycoconjugates are a class of complex molecules that are widely distributed in the plant kingdom and in some marine organisms. This class of compounds has a wide range of biological activities such as anti-inflammatory, antimicrobial, antifungal, anticancer, antiulcer, and immunoenhancing actions.1-3 Some of them also show various toxic activities such as cytotoxic, hemolytic, cardiotoxic, and teratogenic. Among these compounds, steroidal and triterpenoid saponins have long been known as components of widely used herbal drugs and pharmaceutical preparations; ginseng, Tribulus terrestris, Quillaja saponaria, and Digitalis ssp. are just a few examples. Thus, identification of saponins in herbal drugs used worldwide is of significance in phytochemical and toxicological quality control studies, and for the production of safe health products. Therefore, there is continuing demand for methods to rapidly identify and characterize these natural products.     

双-β-咔啉衍生物的设计、合成及抗肿瘤活性

以去氢骆驼蓬碱为原料,经过脱甲基、烷基化等步骤,合成了一系列双-β-咔啉衍生物.目标化合物均经核磁共振谱(NMR)和质谱(MS)进行结构确证.以顺铂为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Bel-7402,786-0,BGC-823,A375,769-P和MCF7等6株细胞)活性.结果表明,化合物4g和4o与阳性对照药相比具有良好的抗肿瘤活性,其半抑制浓度(IC_(50))值均小于10μmol/L.初步构效关系研究表明,当桥链亚甲基数目为8~10,β-咔啉环上9-丁基或9-异丁基取代时,化合物的抗肿瘤活性较强.     

Six new triterpenoid saponins from the leaves of Ilex oblonga and their inhibitory activities against TMV replication

Six new triterpenoid saponins of the ursane types were isolated from the MeOH extract of the leaves of Ilex oblonga. They were oblonganoside A (1), oblonganoside B (2), oblonganoside C (6), oblonganoside D (8), oblonganoside E (9), and oblonganoside F (10), together with three known triterpenoid saponins. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and compound 1 showed appreciable inhibitory activity against TMV replication with EC50 value 0.074 mM.     

双-β-咔啉衍生物的设计、合成及抗肿瘤活性

以去氢骆驼蓬碱为原料, 经过脱甲基、 烷基化等步骤, 合成了一系列双-β-咔啉衍生物. 目标化合物均经核磁共振谱(NMR)和质谱(MS)进行结构确证. 以顺铂为阳性对照药, 采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Bel-7402, 786-0, BGC-823, A375, 769-P和MCF7等6株细胞)活性. 结果表明, 化合物4g和4o与阳性对照药相比具有良好的抗肿瘤活性, 其半抑制浓度(IC₅₀)值均小于10 μmol/L. 初步构效关系研究表明, 当桥链亚甲基数目为8~10, β-咔啉环上9-丁基或9-异丁基取代时, 化合物的抗肿瘤活性较强.     

开口箭化学成分及抗肿瘤活性

从开口箭新鲜根茎中分离得到8个化合物, 通过理化性质分析、 质谱、 红外光谱及核磁共振波谱检测等方法鉴定了其结构, 分别为开口箭皂苷J(1)、 (25S)-26-O-β-D-吡喃葡萄糖基呋甾-1β,3β,22α,26-四羟基-3-O-β-D-吡喃葡萄糖苷(2)、 洋地黄毒苷元-3-O-α-L-吡喃岩藻糖苷(3)、 弯蕊皂苷元B(4)、 异罗斯考皂苷元(5)、 罗斯考皂苷元(6)、 香豌豆酚(7)及(+)-儿茶素(8). 其中, 化合物1为新化合物, 化合物3, 4, 7和8为首次从该属植物中分离得到. 在抗人结肠癌细胞LoVo和胃癌细胞BGC-823活性评价中, 化合物5和6表现出较强的抗肿瘤活性, 半抑制浓度(IC₅₀)值分别达到0.532和0.757 μmol/L.     

Two new triterpenoid glycosides isolated from Aesculus assamica GRIFF

Phytochemical study of the ethanol extract of the seeds of Aesculus assamica led to the isolation of two new triterpenoid saponins. The structure of the new compounds were elucidated on the basis of spectral data to be 28-O-acetyl-21-O-(4-O-angeloyl)-6-deoxy-beta-glucopyranosyl-3-O-[beta-glucopyranosyl(1-2)-O-[beta-glucopyranosyl(1-4)]-beta-glucuronopyranosyl]protoaescigenin (1), and 21-O-(4-O-angeloyl)-6-deoxy-beta-glucopyranosyl-3-O-[beta-glucopyranosyl(1-2)-O-[beta-glucopyranosyl(1-4)]-beta-glucuronopyranosyl]protoaescigenin (2). Their in vitro bioactivity against plant pathogenic fungus Pyricularia oryzae and cytotoxicity against K562 and HCT-15 cell lines were evaluated.     

Two New Triterpenoid Saponins from Stauntonia obovatifoliola Hayata ssp. intermedia

Two new hederagenin‐type saponins, staunoside G ( 1 ) and staunoside H ( 2 ), along with twelve known triterpenoid saponins, were isolated from stems of Stauntonia obovatifoliola Hayata ssp. intermedia. Their structures were determined by analysis of HR‐EI‐MS, and 1D‐ and 2D‐NMR data, and comparison with those in literature. The two new compounds showed moderate cytotoxicities against three tumor cells, i.e., A549 (lung carcinoma), 4T1 (mammary carcinoma), and HeLa (cervical carcinoma).     

Cytotoxic triterpenoid saponins from the roots of Platycodon grandiflorum

Bioguided fractionation of the ethanol extracts obtained from Platycodon grandiflorum roots led to isolation of two new triterpenoid saponins, characterized as 3-O-beta-D-glucopyranosyl-2beta,12alpha,16alpha,23,24-pentahydroxyoleanane-28(13)-lactone (1) and 3-O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-2beta,12alpha,16alpha,23alpha-tetrahydroxyoleanane-28(13)-lactone (2) by 1D- and 2D-NMR and MS techniques, as well as chemical means. Both compounds showed cytotoxic activity against human ECA-109 cells.     

Rapid structural characterization of triterpenoid saponins in crude extract from Symplocos chinensis using liquid chromatography combined with electrospray ionization tandem mass spectrometry

Triterpenoid saponins in bioactive crude extract from Symplocos chinensis were rapidly identified using electrospray ionization multi-stage tandem mass spectrometry (ESI-MSn) and liquid chromatography coupled with sequential mass spectrometry (LC-MSn). According to the characteristic fragmentation behavior of known glucuronide-type triterpenoid saponins isolated from this plant, a total of fourteen constituents in the crude extract were structurally characterized on the basis of their retention time and tandem mass spectrometric analysis, including five pairs of naturally occurring isomers. Except one known saponin formerly obtained, the other constituents were new compounds. The analytical method of LC-MSn combined with ESI-MSn in positive and negative ion modes has been developed for the direct structural elucidation of triterpenoid saponins of this kind in plant extracts.     

Characteristic fragmentation behavior of some glucuronide-type triterpenoid saponins using electrospray ionization tandem mass spectrometry

The fragmentation behavior of some glucuronide-type triterpenoid saponins from Symplocos chinensis, and their analogues escin Ia and Ib, were investigated by positive ion electrospray ionization tandem mass spectrometry using a quadrupole linear ion trap mass spectrometer. The fragmentation patterns of these saponins significantly changed in accordance with structural variations in the glucuronyl residue of the oligosaccharide chain. It was found that the carboxyl group and hydroxyl group at the C-3' position of the glucuronyl residue were the key sites for determining the fragmentation behavior of these compounds. When the carboxyl group was esterified, only the C(2alpha) ion, and no B(2alpha) ion, and cationized aglycone were observed. When the hydroxyl group at C-3' was acylated, the inherent cross-ring cleavage was hindered. However, glycosidic cleavages always occurred, regardless of the crucial structural variations. The results of the present studies can benefit the determination of trace triterpenoid saponins of this type in crude plant extracts, and also provide background information to aid the structural investigations of similar glycoconjugates.     

Triterpene Saponins from <i>Pleurospermum kamtschaticum</i> and Their Biological Activity

Eleven new triterpene saponins (1-11), together with fourteen known triterpene and triterpene saponins (12-25) were isolated from a MeOH extract of Pleurospermum kamtschaticum HOFFMANN (Umbelliferae). The chemical structures of the new compounds (1-11) were determined by means of MS, ¹H-NMR, ¹³C-NMR, correlated spectroscopy (COSY), heteronuclear multiple bond correlation (HMBC), total correlated spectroscopy (TOCSY) and nuclear Overhauser effect spectroscopy (NOESY) to be pleurosaponin A (1)-K (11). The isolated compounds were tested for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, HCT15) in vitro using the sulforhodamine B bioassay (SRB) assay. All compounds showed little cytotoxicity against tested cell lines (IC50 >30?μM).     

Three new triterpenoid saponins from the roots of Ardisia crenata and their cytotoxic activities

Three new triterpenoid saponins, ardisicrenoside O (1), ardisicrenoside P (2) and ardisicrenoside Q (3) together with three known compounds, 3β,16α-dihydroxy-30-methoxy-28, 30-epoxy-olean-12-en, cyclamiretin A 3-O-β-d-glucopyranosyl-(1→2) -α-l-arabinopyranoside and cyclamiretin A 3-O-β-d-glucopyranosyl-(1→4) -α-l-arabinopyranoside were isolated from the roots of Ardisia crenata Sims. Their structures were determined by one- and two-dimensional NMR techniques, including HSQC, HMBC and TOCSY experiments, as well as acid hydrolysis and GC analysis. All isolates were evaluated for the cytotoxic activities on two human cancer cell lines and compounds 3, 5 and 6 showed significant cytotoxicity.     

Cytotoxicity of two triterpenoids from Nigella glandulifera

During an investigation of antitumor substances from Nigella glandulifera Freyn et Sint. (Ranunculaceae) the cytotoxicity of two oleanane triterpene saponins isolated from the seeds of this species, kalopanaxsaponins A and I, was evaluated against HepG2, drug resistant HepG2 (R-HepG2) (two hepatocyte cell lines) and primary cultured normal mouse hepatocytes. Evident cytotoxic activities were observed. Morphological observations and cell cycle analysis suggest that these compounds inhibit the proliferation of hepatoma by inducing apoptosis and consequently kalopanaxsaponins A and I may be potential therapeutic agents for the treatment of parental and drug resistant hepatoma.