Cytotoxic steroidal glycosides from Allium flavum

Three new spirostane-type glycosides (1–3) were isolated from the whole plant of Allium flavum. Their structures were elucidated mainly by 2D NMR spectroscopic analysis and mass spectrometry as (20S,25R)-2α-hydroxyspirost-5-en-3β-yl O-β-d-xylopyranosyl-(1 → 3)-[β-d-galactopyranosyl-(1→2)]-β-d-galactopyranosyl-(1→4)-β-d-galactopyranoside (1), (20S,25R)-2α-hydroxyspirost-5-en-3β-yl O-β-d-xylopyranosyl-(1 → 3)-[β-d-glucopyranosyl-(1→2)]-β-d-galactopyranosyl-(1→4)-β-d-galactopyranoside (2), and (20S,25R)-spirost-5-en-3β-yl O-α-l-rhamnopyranosyl-(1 → 4)-[β-d-glucopyranosyl-(1→2)]-β-d-glucopyranoside (3). The three saponins were evaluated for cytotoxicity against a human cancer cell line (colorectal SW480).     

Five new cyotoxic steroidal glycosides from the fruits of Solanum torvum

The fruits of Solanum torvum Swartz, commonly known as Turkey berry, are edible and commonly used as a vegetable in the South Indian population's diet and as an essential ingredient in Thai cuisine. Five new steroidal glycosides together with five known ones were isolated from the fruits of S. torvum Swartz. Based on chemical and spectral evidence, the five new compounds were identified to be 25(S)-26-O-β-d-glucopyranosyl-5α-furost-22(20)-en-3β,6α,26-triol-6-O-[α-l-rhamnopyranosyl-(1 → 3)-O-β-d-quinovopyranoside] (1), 25(S)-26-O-β-d-glucopyranosyl-5α-furost-22(20)-en-3-one-6α,26-diol-6-O-[α-l-rhamnopyranosyl-(1 → 3)-O-β-d-quinovopyranoside] (2), 25(S)-26-O-β-d-glucopyranosyl-5α-furost-22(20)-en-3β,6α,26-triol-6-O-β-d-quinovopyranoside (3), 5α-pregn-16-en-20-one-3β,6α-diol-6-O-[α-l-rhamnopyranosyl-(1 → 3)-β-d-quinovopyranoside] (4), and 5α-pregn-16-en-3,20-dione-6α-ol-6-O-[α-l-rhamnopyranosyl-(1 → 3)-β-d-quinovopyranoside] (5). These new compounds were assayed for cytotoxicities in vitro, and 1 to 4 showed cyotoxic activity against the human melanoma cell line A375, with IC₅₀ values of 30 μM to 260 μM.     

Sibiricasaponins A–E,five new triterpenoid saponins from the aerial parts of Polygala sibirica L.

Five new triterpenoid saponins, named as sibiricasaponins A–E (1–5), were isolated and identified from the aerial parts of Polygala sibirica L., together with nine known triterpenoid saponins (6–14). The chemical structures of the five new triterpenoid saponins (1–5) were elucidated as 3β,19α-dihydroxyurso-12-ene-23,28-dioic acid 3-O-β-d-glucuronopyranoside (1), pomolic acid 3-O-(3-O-sulfo)-α-l-arabinopyranoside (2), pomolic acid 3-O-(4-O-sulfo)-β-d-xylopyranoside (3), pomolic acid 3-O-(2-O-acetyl-3-O-sulfo)-α-l-arabinopyranoside (4), and 3-O-β-d-glucopyranosyl medicagenic acid 28-O-β-d-galactopyranosyl (1 → 4)-β-d-xylopyranosyl (1 → 4)-α-l-rhamnopyranosyl (1 → 2)-(4-O-acetyl)-[β-d-apiofuranosyl (1 → 3)]-β-d-fucopyranosyl ester (5), respectively, on the basis of spectroscopic data and physicochemical evidences. These isolated compounds (1–14) were evaluated for their anti-ischemic effects on oxygen/glucose deprivation (OGD) model in vitro, and only compound 7 showed a weak anti-ischemia effect, with EC₅₀ value of 46.7 μM.     

New cytotoxic triterpenoid saponins from the whole plant of Clematis lasiandra Maxim

Four new oleanane type triterpenoid saponins (1–4) and three known saponins (5–7) were isolated from the whole plant of Clematis lasiandra Maxim. The structures of the four new compounds were elucidated as 3-O-β-d-ribopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 4)]-β-d-xylopyranosyl hederagenin (1), 3-O-β-d-ribopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-β-d-xylopyranosyl oleanolic acid 28-O-β-d-glucopyranosyl ester (2), 3-O-β-d-ribopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-β-d-xylopyranosyl hederagenin (3) and 3-O-β-d-ribopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-[β-d-glucopyranosyl-(1 → 4)]-α-l-arabinopyranosyl hederagenin (4) on the basis of extensive spectroscopic analysis and chemical evidence. Compounds 1–7 were evaluated for their cytotoxicity against human tumor cell lines HL-60, Hep-G2 and SGC-7901, and all of the evaluated saponins showed significant cytotoxicity to those three tumor cell lines with IC₅₀ in the range from 1.40 to 19.50 μmol/L except for compounds 2 and 6.     

Phenylethanoid glycosides from the stems of Callicarpa peii (hemostatic drug)

Two new trisaccharide intermediates of phenylethanoid glycosides, peiioside A₁/A₂ (1a/1b) and peiioside B (2), were isolated from the n-BuOH fraction of MeOH extract of the stems of Callicarpa peii H.T. Chang, together with five biogenetic relevant known compounds 3–7. The structures of compounds 1 and 2 were elucidated by extensive spectroscopic methods (especially 2D-NMR techniques) and acid-catalyzed hydrolysis as O-α-l-rhamnopyranosyl-(1″ → 3′)-O-[β-d-apiofuranosyl-(1‴ → 6′)] -4′-O-[(E)-caffeoyl]-d-glucopyranoside] (1a/1b), 3,4-dihydroxy-β-phenylethoxy-O-[β-d-apiofuranosyl-(1‴ → 6′)-α-l-rhamnopyranosyl-(1″ → 3′)-O-β-d-glucopyranoside] (2), respectively. On the basis of the isolated compounds, a presumable biogenetic pathway of the biologically interesting phenylethanoid glycosides about forsythoside B (3) and acteoside (4) isolated from this species was proposed. Isolation of five related intermediates (1–2, 5–7) provided further support for the biogenetic path. This is the first report about phytochemical research on C. peii and the biogenetic hypothesis of forsythoside B and acteoside.     

Chemical constituents of Swertia yunnanensis and their anti-hepatitis B virus activity

Four new triterpenoids, sweriyunnangenin A (1), sweriyunnanosides A (2), B (3) and C (4), along with nineteen known compounds (5–23) were isolated from Swertia yunnanensis. Based on extensive spectroscopic analyses (1D- and 2D-NMR, HRESIMS, UV, IR, [α]_D), the structures of sweriyunnangenin A (1), sweriyunnanosides A (2), B (3) and C (4) were elucidated as taraxer-14-ene-3α,6β-diol, oleanolic acid 28-O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranoside, 2α,3β-di-hydroxyolean-12-en-28-oic acid 28-O-β-d-glucopyranosyl(1 → 6)-β-d-glucopyranosyl (1 → 6)-β-d-glucopyranosyl(1 → 2)-β-d-glucopyranoside and hederagenin 28-O-β-d-glucopyranosyl(1 → 6)-β-d-glucopyranosyl(1 → 6)-β-d-glucopyranosyl(1 → 2)-β-d-glucopyranoside, respectively. Twenty-two compounds were evaluated for their anti-HBV activities on the HepG 2.2.15 cell line in vitro, of which nine compounds showed potent anti-HBV activities. Compounds 1, 5–6, 14–16 and 19 showed activities against the secretion of HBsAg (IC₅₀ values from 0.10 to 1.76 mM) and HBeAg (IC₅₀ values from 0.04 to 1.41 mM), and compounds 11 and 13–16 exhibited significant inhibition on HBV DNA replication (IC₅₀ values from 0.01 to 0.09 mM).     

Two new steroidal saponins from Selaginella uncinata (Desv.) Spring and their protective effect against anoxia

Four steroidal saponins were isolated from the anti-anoxic fraction of the 60% EtOH extract of Selaginella uncinata, including two new compounds, (3β, 7β, 12β, 25R)-spirost-5-ene-3, 7, 12-triol-3-O-α-L-rhamnopyranosyl-(1 → 2)-O-[α-L-rhamnopyranosyl-(1 → 4)]-O-β-d-glucopyranoside (1), (2α, 3β, 12β, 25R)-spirost-5-ene-2, 3, 12-triol-3-O-α-L-rhamnopyranosyl-(1 → 2)-O-[α-L-rhamnopyranosyl-(1 → 4)]-O-β-d-glucopyranoside (2) and two known compounds, (3β, 12β, 25R)-spirost-5-ene-3,12-diol-3-O-α-L-rhamnopyranosyl-(1 → 2)-O-[α-L-rhamnopyranosyl-(1 → 4)]-O-β-d-glucopyranoside, (3), (1α, 3β, 25R)-spirost-5-ene-2-diol-3-O-α-L-rhamnopyranosyl-(1 → 2)-O-[α-L-rhamnopyranosyl(1 → 4)]-O-β-d-glucopyranoside (4). The four compounds showed potent protective effect against anoxia in the anoxic PC12 cells assay, among which compounds 1 and 2 were the most active. To our knowledge, this is the first study to report the steroidal saponins in the plant S. uncinata and demonstrate their protective effect against anoxia in PC12 cell assay.     

Five new triterpenoidal saponins from the roots of Ilex cornuta and their protective effects against H2O2-induced cardiomyocytes injury

Five new ursane-type triterpenoidal saponins (1–5), together with five known ones (6–10), were isolated from the EtOH extract of the roots of Ilex cornuta. The structures of saponins 1–5 were elucidated as 19α-hydroxyurs-12-en-28-oic acid 3β-O-β-D-glucuronopyranoside (1), 19α-hydroxyurs-12-en-28-oic acid 3β-O-β-D-glucuronopyranoside-6-O-ethyl ester (2), 19α-hydroxyurs-12-en-28-oic acid 3β-O-α-L-arabinopyranosyl-(1 → 2)-β-D-glucuronopyranoside (3), 3β-O-[α-L-arabinopyranosyl-(1 → 2)-β-D-glucuronopyranosyl]-19α-hydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranosyl ester (4) and 3β-O-[α-L-arabinopyranosyl-(1 → 2)-β-D-glucuronopyranoside-6-O-methyl ester]-19α-hydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranosyl ester (5), on the basis of spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR) and chemical reactions. Protective effects of compounds 1–10 against H₂O₂-induced H9c2 cardiomyocyte injury were tested. Compounds 1–5, 7, and 10 showed cell-protective effects. Among them compound 5 exhibited the highest activity. No significant DPPH radical scavenging activity was observed for compounds 1–10.     

Two novel saponins of 20, 26-epoxy derivatives of pseudojujubogenin from the seeds of Hovenia trichocarpa

Two new saponins of 20, 26-epoxy derivatives of pseudojujubogenin, hoduloside XI (1) and hoduloside XII (2) were isolated from the seeds of Hovenia trichocarpa. The structures of the new compounds were established by extensive NMR experiments and chemical methods. Hoduloside XI was confirmed to be 3-O-{β-d-glucopyranosyl(1 → 3)-[β-d-xylopyranosyl(1 → 2)]-α-l-arabinopyranosyl}-20, 26-epoxypseudojujubogenin. Hoduloside XII was identified as 3-O-{β-d-xylopyranose(1 → 2)glucopyranosyl(1 → 3)[rhamnopyranose(1 → 2)]β-d-glucopyranosyl}-20, 26-epoxypseudojujubogenin. The in vitro cytotoxic activity of compounds 1 and 2 was assayed. They displayed inhibitive activities against human cancer cell lines HL60 and K562.     

Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia capillaris

Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S-trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-β -D-glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-β -D-glucopyranose (4), together with 34 known compounds were isolated from Artemisia capillaris. The structures of the new compounds were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [α]_D and CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25 compounds possessed inhibitory activity against HBV DNA replication according to our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12 could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA replication with IC₅₀ values of 15.02 μM (SI = 111.3), 9.00 μM (SI = 185.9) and 12.01 μM (SI = 139.2).     

Cytotoxic cucurbitane triterpenoids isolated from the rhizomes of Hemsleya amabilis

Two new cucurbitane triterpenoids, 7β-hydroxycucurbitacin F-25-O-acetate (1) and 2β,3β,20(S),26,27-pentahydroxy-16α,23(S)-epoxycucurbita-5,24-dien-11-one (2) along with eleven known cucurbitane triterpenoids (3–13, resp.) were isolated from the rhizomes of Hemsleya amabilis Diels. The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of the isolated cucurbitane triterpenoids were evaluated against the HeLa human cancer cell lines. Hemslecin A (5), the main ingredient of H. amabilis, exhibited the significant cytotoxicity with IC₅₀ value of 0.389 μM.     

Glycosylsphingolipids from Euonymus japonicus Thunb

The stem bark of Euonymus japonicus Thunb. led to the isolation of three new glycosylsphingolipids (1–3), 1-O-[-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranosyl]-(2S,3R,9E)-2-N-[(2R)-hydroxystearoyl]-octadecasphinga-9-ene (euojaposphingoside A, 1), 1-O-[β-D-glucopyranosyl-(1 → 2)-β-D-glucopyranosyl]-(2S,3R,4R,11E)-2-N-[(2R)-hydroxydocasanoyl]-octadecasphinga-11-ene (euojaposphingoside B, 2), 1-O-[β-D-glucopyranosyl]-2′-O-[β-D-glucopyranosyl]-(2S,3R,4R,11E)-2-N-[(2R)-hydroxytetracosanoyl]-octadecasphinga-11-ene (euojaposphingoside C, 3) along with three known glycosylsphingolipids (4–6), 1-O-[β-D-glucopyranosyl]-(2S,3R,9E)-3-hydroxymethyl-2-N-[(2R)-hydroxynonacosanoyl)-tridecasphinga-9-ene (4), 1-O-[β-D-glucopyranosyl]-(2S,3R,9E,12E)-2-N-[(2R)-hydroxytetracosanoyl] octadecasphinga-9,12–diene (5), 1-O-[β-D-glucopyranosyl]-(2S,3R,5R,9E)-2-N-[tridecanoyl] nonacosasphinga-9-ene (6), lupeol (7), stigmasterol (8), sitosterol (β and α) (9,10) and β-carotene (11). The structure of all the compounds was achieved by spectroscopic and chemical data analysis. The antiplasmodial, antileismanial and cytotoxic activity of all compounds was tested.     

Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica

Fourteen sterols (1–14), including two new sterols, trihydroxysitosterol (2) and 5α,6β,7α-7α-acetoxysitosterol (3), were isolated from the branches and leaves of Phyllanthus emblica L. The isolated compounds and a structurally related sterol 15 from Aphanamixis grandifolia were screened for cytotoxicity in two tumor cell lines (HL-60 and SMMC-7721) and a non-tumor cell line (HL-7702) using RSB assay. Within the series of phytosterol derivatives tested, compound 15 was the most active, displaying potent cytotoxicity against HL-60 with IC₅₀ of 5.10 μmol/L, and most of the active compounds showed selective cytotoxicity against tumor and non-tumor cell lines, especially compound 10 with a safety index of 4.42.     

New cytotoxic compounds from flowers of Lawsonia inermis L.

Three new compounds, a bicoumarin A (1), a biflavonoid A (2), and a biquinone A (3), as well as 12 other known compounds, were isolated from the flower of Lawsonia inermis L. The structures were elucidated by spectral analysis and new compounds 2 and 3 then were further confirmed by ECD calculations and single-crystal X-ray diffraction crystallography respectively. The cytotoxicity of the compounds against four cancer cell lines, including MCF-7, Hela, HCT-116, and HT-29 were evaluated using MTT assay. The IC₅₀ values of compounds 3 and 5 against MCF-7, Hela, HCT-116, and HT-29 were 2.24, 1.42, 24.29, and 7.02 μM and 6.1, 2.44, 5.58, and 10.21 μM respectively. The two compounds exhibited stronger inhibitory activities than the positive control 5-fluorouracil (IC₅₀ = 7.34, 11.50, 36.17, 18.83 μM) against the four tested cell lines. These results demonstrated that compounds from the flowers of L. inermis L. showed cytotoxic activity on MCF-7, Hela, HCT-116, and HT-29 cell lines.     

Triterpenoids of sour jujube show pronounced inhibitory effect on human tumor cells and antioxidant activity

Sour jujube is a common fruit and traditional medicine in China. Bioactivity-guided fractionation of sour jujube was used to determine the chemical identity of potent antiproliferative and antioxidant constituents. Four novel ursane-type triterpenoids, together with 8 known were isolated and identified. The new triterpenoids were elucidated to be 2α,3β,13β,23-tetrahydroxy-urs-11-en-28-oic acid (3), 2α,3β-dihydroxy-urs-20(30)-en-28-oic acid (9), 2α,3β,28-trihydroxy-urs-20(30)-ene (10), and 3β,12β,13β-trihydroxy-ursan-28-oic acid (11). Among the triterpenoids isolated, 2α,3β,19α-trihydroxy-urs-12-en-28-oic acid (7), 9 and 10 showed high potent inhibitory activity toward the proliferation of HepG2 cells, which the IC₅₀ values were lower than 5 μM. Compounds 9 and 10 also exhibited pronounced activity against MCF-7 cells, with IC₅₀ value of 0.8 ± 0.03 and 1.5 ± 0.1 μM, respectively. Compound 10 showed high antioxidant activity with an EC₅₀ of 0.8 ± 0.02 μM, which was 18.9 times higher than ascorbic acid in antioxidant capacity.     

Triterpenoids from the fruits of Azadirachta indica (Meliaceae)

Four new triterpenoids, indicalilacols A-D (1–4), were isolated from the MeOH extract of the fruits of Azadirachta indica, including a new 19(10 → 9β)abeo-tirucallane derivative, two new tirucallane-type triterpenoids, and a new euphane-type triterpenoid, along with three known tirucallane-type triterpenoids. Their structures were elucidated on the basis of spectroscopic analyses. The absolute configuration of 2 was elucidated by the chemical conversion of 2 into 21-oxo-melianodiol 24,25-acetonide. Compounds 2, 6–8 exhibited moderate cytotoxicity against three human cancer cell lines, including multidrug-resistant (MDR) cancer cells (KB-C2). Although compound 5 was not cytotoxic against any of the tested cancer cell lines, 5 showed cytotoxicity against KB-C2 cells in the presence of 2.5 μM colchicine, suggesting that 5 might have an MDR-reversal effect.     

Sesquiterpene coumarin and sesquiterpene chromone derivatives from Ferula ferulaeoides (Steud.) Korov.

Five novel compounds — three sesquiterpene coumarin derivatives, ferulin A (1), B (2), and C (3), and two sesquiterpene chromone derivatives, ferulin D (4) and E (5), together with eleven known compounds (6–16) have been isolated from the roots of Ferula ferulaeoides (Steud.) Korov. Their structures were established by comprehensive spectroscopic analysis. The biosynthetic pathways leading to these compounds were proposed. The cytotoxicity of all these isolates against HepG2, MCF-7, and C6 cancer cell lines was evaluated and compound 7 displayed the highest potency against HepG2, MCF-7, and C6 with IC₅₀ values 39.9 μM, 37.7 μM, and 16.0 μM, respectively.     

Xanthine oxidase inhibitory lanostanoids from Ganoderma tsugae

Two new lanostanoids, 3α-acetoxy-22-oxo-5α-lanosta-8,24-dien-21-oic acid, named tsugaric acid D (1) and 16α-hydroxy-3-oxo-5α-lanosta-6,8,24(24¹)-trien-21-oic acid, named tsugaric acid E (2) were isolated from the fruit bodies of Ganoderma tsugae. The structures 1 and 2 were determined by spectroscopic methods. Compound 1 and known compounds 3 and 6 exhibited significant inhibitory effects on xanthine oxidase (XO) activity with an IC₅₀ values of 90.2 ± 24.2, 116.1 ± 3.0, and 181.9 ± 5.8 μM, respectively. Known compound 5 was able to protect human keratinocytes against damage induced by UVB light, which showed 5 could protect keratinocytes from photodamage. The 1 and 5 μM 1 combined with 5 μM cisplatin, respectively, enhanced the cytotoxicity induced by cisplatin. It suggested that 1 and 5 μM 1 combined with low dose of cisplatin may enhance the therapeutic efficacy of cisplatin and reduce side effect and cisplatin resistant.     

Pregnane alkaloids from Sarcococca hookeriana var. digyna

Fourteen pregnane-type steroidal alkaloids were isolated from the ethanolic extracts of whole Sarcococca hookeriana var. digyna plants. Their structures were elucidated on the basis of spectral data. Three of them were identified as new steroidal alkaloids: (S)-20-(N,N-dimethylamino)-16α,17α-epoxy-3β-methoxy-pregn-5-ene (1), (20S)-20-(N,N-dimethylamino)-3β-tigloylamino-5α-pregn-11β-ol (2), and (20S)-2α,4β-bis(acetoxy)-20-(N,N-dimethylamino)-3β-tigloylamino-5α-pregnane (3). Some of the isolated compounds showed estrogen biosynthesis-promoting effects in human ovarian granulosa-like KGN cells. The EC₅₀ values for the most effective compounds, vagnine B (6) and funtumafrine C (12), were 71 μM and 67 μM, respectively.     

Osteoclast-inhibiting saikosaponin derivatives from Bupleurum Chinense

Five new saikosaponins, saikosaponin w (1), 21β-hydroxysaikosaponin b₂ (2), 6″-O-acetylsaikosaponin e (3), 6″-O-acetylsaikosaponin b₁ (4), and 6″-O-acetylsaikosaponin b₃ (5), along with twenty-two known ones (6–27), have been isolated from the roots of Bupleurum chinense. Their structures were elucidated on the basis of detailed spectroscopic analysis, including mainly 1D and 2D NMR and HRESI-MS, qualitative chemical methods, and comparison with the literatures. Osteoclast-inhibiting activity of some of the isolated compounds was evaluated in vitro, with five ones have shown significant activity by inhibitory rates ranging from 48.3% to 56.1% at the concentration of 10 μM and with significant differences among groups observed.