Cycloartane and oleanane-type glycosides from Astragalus pennatulus.

Four new cycloartane and one new oleanane-type glycosides were isolated from Astragalus pennatulus along with five known cycloartane-type glycosides. The structures of the new compounds were established as 3-O-ß-D-xylopyranosyl-6-O-ß-D-glucopyranosyl-3ß,6α,16ß-trihydroxy-24-oxo-20(R),25-epoxycycloartane (1), 3-O-[ß-D-glucuronopyranosyl-(1 → 2)-ß-D-xylopyranosyl]-3ß,16ß,24α-trihydroxy-20(R),25-epoxycycloartane (2), 3-O-[ß-D-glucuronopyranosyl-(1 → 2)-ß-D-xylopyranosyl]-3ß,16ß,25-trihydroxy-20(R),24(S)-epoxycycloartane (3), 3,25-di-O-ß-D-glucopyranosyl-6-O-ß-D-xylopyranosyl-3ß,6α,16ß,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (4), 29-O-α-L-rhamnopyranosyl-abrisapogenol B (5) by 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. The aglycone of compound 1, 3ß,6α,16ß-trihydroxy-24-oxo-20(R),25-epoxycycloartane, is reported for the first time. The cytotoxic activity of the isolated compounds was evaluated against three cancer cell lines including A549 (human lung adenocarcinoma), A375 (human melanoma) and DeFew (human B lymphoma) cells. None of the tested compounds caused a significant reduction of the cell number.

Synthesis, antimicrobial and cytotoxic activities, and structure-activity relationships of gypsogenin derivatives against human cancer cells.

A series of gypsogenin (1) derivatives (1a-i) was synthesized in good yields, and the derivatives' structures were established using UV, IR, (1)H NMR, (13)C NMR, and LCMS spectroscopic data. Among the tested compounds, 1a, 1b, 1d, 1e, and gypsogenin (1) showed antimicrobial activities against Bacillus subtilis and Bacillus thrungiensis, with inhibition zones of 10-14 mm. In addition, compounds 1b, 1d, and 1e showed antimicrobial activities against Bacillus cereus, with inhibition zones of 9-14 mm. Using six human cancer cell lines in vitro, the cytotoxic activities of all tested compounds were determined by calculating the IC50 values. Doxorubicin and paclitaxel were used as controls. Among the tested compounds, 1a, 1c, and 1d had inhibitory effects with IC50 values of 3.9 µM (HL-60 cells), 5.15 µM (MCF-7 cells), and 5.978 µM (HL-60), respectively. To determine the type of cell death, Hoechst 33258 (HO) and propidium iodide (PI) double staining was used. Especially, gypsogenin (1) and compound 1a triggered the apoptotic mechanism at a concentration of 20 µM. Thus, gypsogenin (1) and compounds 1a, 1c, and 1d possess varying degrees of biological activities and can be considered as potential antitumor agents.

Cycloartane glycosides from Astragalus plumosus var. krugianus and evaluation of their antioxidant potential.

The methanol extracts of Astragalus plumosus var. krugianus Chamb. & Matthews afforded sixteen cycloartane glycosides among which krugianoside A, was never reported before. All compounds were evaluated for their cytotoxic activity in human skin fibroblast WS1 cells. For compounds exhibiting no significant effect on WS1 viability, the antioxidant potential was examined. Compounds 1 and 8 prevented elevation of ROS induced by t-BOOH, suggesting the potential activity of these compounds to protect fibroblasts from oxidative stress.

Oleanane type glycosides from Paronychia anatolica subsp. balansae.

Four new oleanane-type triterpene glycosides were isolated from the methanol extract of the roots of Paronychia anatolica subsp. balansae along with three known oleanane-type triterpene glycosides. Structures of the new compounds were established as 3-O-ß-D-glucuronopyranosyl-28-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-quinovopyranoside] zahnic acid, 3-O-ß-D-glucuronopyranosyl-28-O-[ß-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-ß-D-quinovopyranoside] zahnic acid, 3-O-ß-D-glucuronopyranosyl-28-O-[α-L-arabinofuranosyl-(1→2)-ß-D-quinovopyranoside] zahnic acid, 28-O-[α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl]-medicagenic acid, by using 1D and 2D-NMR techniques and mass spectrometry. The cytotoxic activity of the isolated compounds was evaluated against a small panel of cancer cell lines including human breast cancer (MCF-7), human lung adenocarcinoma (A549) and human leukemia (U937) cell lines.

Unusual secondary metabolites from Astragalus halicacabus LAM.

From the whole plant of Astragalus halicacabus (Sect. Halicacabus), a new cycloartane-type glycoside, (20R,24S)-3-O-[α-L-arabinopyranosyl-(1→2)-ß-D-xylopyranosyl]-20,24-epoxy-16-O-ß-D-glucopyranosyl-3ß,6α,16ß,25-tetrahydroxycycloartane, and a new glycoside, 3-O-[ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranosyl]maltol were isolated together with seven known cycloartane-type glycosides, i.e., cyclocanthoside D, askendosides D, F, and G, cyclosieversioside G, cyclostipuloside A, elongatoside, and a known maltol glucoside, 3-O-ß-D-glucopyranosylmaltol. The structures were elucidated by means of high-resolution mass spectrometry, and extensive 1D- and 2D-NMR spectroscopic analysis. This is the first phytochemical work on A. halicacabus, and a maltol glycoside was encountered for the first time in the Leguminosae family.

Analysis of saponins and phenolic compounds as inhibitors of α-carbonic anhydrase isoenzymes.

A series of phenolic and saponin type natural products such as quercetin, rutin, catechin, epicatechin, silymarin, trojanoside H, astragaloside IV, astragaloside VIII and astrasieversianin X, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). We here report inhibitory effects of these compounds against five α-CA isozymes (hCA I, hCA II, bCA III, hCA IV and hCA VI). Most of the phenolic and saponin type compounds inhibited the isoenzymes quite effectively at low micromolar K(I)-s ranging between 0.1 and 4 µM, whereas a few derivatives were ineffective (K(I)-s > 100 µM). The results were remarkable which might lead to design of novel CAIs with a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors.

Oleanane glycosides from Astragalus tauricolus: isolation and structural elucidation based on a preliminary liquid chromatography-electrospray ionization tandem mass spectrometry profiling.

As a part of our ongoing research for bioactive compounds from Turkish Astragalus species, the investigation of Astragalus tauricolus has been carried out. An approach based on HPLC-ESIMS(n) experiments has been used to profile the triterpene glycosides occurring in the butanol extract of the whole plant. On the basis of the results of the online screening by HPLC-ESIMS(n), 22 oleanane-type triterpene glycosides, including ten compounds never reported before, were isolated, and their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analysis. Noteworthy, cycloartane-type triterpene glycosides, the main constituents of Astragalus spp., were not found. This peculiar feature characterizes a very limited group of Astragalus spp. The antiproliferative activity of the isolated compounds 1-12, 15, 17-19 was evaluated against a small panel of cancer cell lines. Only compound 11 showed an IC(50) of 22 µM against human leukemia cell line (U937). The other tested compounds, in a range of concentrations between 1 and 50 µM, did not cause any significant reduction of the cell number.

Saponins from Astragalus hareftae (NAB.) SIRJ.

Four cycloartane- (hareftosides A-D) and oleanane-type triterpenoids (hareftoside E) were isolated from Astragalus hareftae along with fifteen known compounds. Structures of the compounds were established as 3,6-di-O-ß-D-xylopyranosyl-3ß,6α,16ß,24(S),25-pentahydroxycycloartane, 3,6,24-tri-O-ß-D-xylopyranosyl-3ß,6α,16ß,24(S),25-pentahydroxycycloartane, 3-O-ß-D-xylopyranosyl-3ß,6α,16ß,25-tetrahydroxy-20(R),25(S)-epoxycycloartane, 16-O-ß-D-glucopyranosyl-3ß,6α,16ß,25-tetrahydroxy-20(R),24(S)-epoxycycloartane, 3-O-[ß-D-xylopyranosyl-(1→2)-O-ß-D-glucopyranosyl-(1→2)-O-ß-D-glucuronopyranosyl]-soyasapogenol B by the extensive use of 1D- and 2D-NMR experiments along with ESI-MS and HR-MS analyses.

Triterpene glycosides from Astragalus angustifolius.

Six new cycloartane-type (1- 6) and four new oleanane-type (7- 10) triterpene glycosides were isolated from Astragalus angustifolius Lam., together with five known triterpene glycosides. Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analysis. Compounds 1- 3 are glycosides of cycloastragenol, while compounds 4- 6 show the C-24 epimer of cycloastragenol as aglycone, encountered for the first time in nature. All compounds were evaluated for their antiproliferative activity in Hela, H-446, HT-29, and U937 cell lines. Only compound 8 displayed a weak activity with IC (50) values of 36 and 50 µM against Hela and HT-29 cell lines, respectively.

Triterpene saponins from Cyclamen hederifolium.

Five triterpene saponins never reported before, hederifoliosides A-E, and four known triterpene saponins were isolated from the tubers of Cyclamen hederifolium. The structures of hederifoliosides A-E were determined as 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-oic acid 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-oic acid 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 3ß,16α-dihydroxy-13ß,28-epoxyolean-30-al 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-[ß-D-glucopyranosyl-(1 → 6)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 30-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-3ß,16α,30-trihydroxyolean-12-en-28-al 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, 30-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-3ß,16α,28,30-tetrahydroxyolean-12-en 3-O-{[ß-D-glucopyranosyl-(1 → 2)-O]-ß-D-xylopyranosyl-(1 → 2)-O-[ß-D-glucopyranosyl-(1 → 3)]-O-ß-D-glucopyranosyl-(1 → 4)-O-α-L-arabinopyranoside}, by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. The cytotoxic activity of the isolated compounds was evaluated against a small panel of cancer cell lines including Hela, H-446, HT-29, and U937. None of the tested compounds, in a range of concentrations between 1 and 50 µM, caused a significant reduction of the cell number.

Cycloartane glycosides from Astragalus aureus.

Eight cycloartane-type triterpene glycosides (1-8) were isolated from Astragalus aureus Willd along with ten known cycloartane-type glycosides (9-18). Their structures were established by the extensive use of 1D and 2D-NMR experiments along with ESIMS and HRMS analyses. Compounds 1-5 are cyclocanthogenin glycosides, whereas compounds 6-8 are based on cyclocephalogenin as aglycon, more unusual in the plant kingdom, so far reported only from Astragalus spp. Moreover, for the first time monoglycosides of cyclocanthogenin (5) and cyclocephalogenin (7, 8) are reported. All of the compounds tested for their cytotoxic activities against a number of cancer cell lines. Among the compounds, only 8 exhibited activity versus human breast cancer (MCF7) at 45 µM concentration.

Secondary metabolites from the roots of Paronychia chionaea.

Two novel secondary metabolites, compounds (1-2) were isolated from the roots of Paronychia chionaea. On the basis of spectroscopic data including 1D and 2D NMR experiments (COSY, TOCSY, HSQC, and HMBC), and mass spectroscopy, their structures were established as 6-C-[alpha-L-arabinopyranosyl-( 1 --> 2)-beta-D-glucopyranosyl]-7-O-[beta-D-glucopyranosyl]-luteolin 3'-methyl ether (1), and 2-(methoxy)-2-(3,5-dimethoxy 4-hydroxyphenyl)-ethane-1,2-diol 1-O-beta-D-glucopyranoside (2).

Phenolic Glycosides with antiproteasomal activity from Centaurea urvillei DC. subsp. urvillei.

A new flavanone glycoside, naringenin-7-O-ß-D-glucuronopyranoside, and a new flavonol glycoside, 6-hydroxykaempferol-7-O-ß-D-glucuronopyranoside were isolated together with 12 known compounds, 5 flavone glycoside; hispidulin-7-O-ß-D-glucuronopyranoside, apigenin-7-O-ß-D-methylglucuronopyranoside, hispidulin-7-O-ß-D-methylglucuronopyranoside, hispidulin-7-O-ß-D-glucopyranoside, apigenin-7-O-ß-D-glucopyranoside, a flavonol; kaempferol, two flavone; apigenin, and luteolin, a flavanone glycoside; eriodictyol-7-O-ß-D-glucuronopyranoside, and three phenol glycoside; arbutin, salidroside, and 3,5-dihydroxyphenethyl alcohol-3-O-ß-D-glucopyranoside from Centaurea urvillei subsp. urvillei. The structure elucidation of the new compounds was achieved by a combination of one- ((1)H and (13)C) and two-dimensional NMR techniques (G-COSY, G-HMQC, and G-HMBC) and LC-ESI-MS. The isolated compounds were tested for their antiproteasomal activity. The results indicated that kaempferol, a well known and widely distributed flavonoid in the plant kingdom, was the most active antiproteasomal agent, followed by apigenin, eriodictyol-7-O-ß-D-glucuronopyranoside, 3,5-dihydroxyphenethyl alcohol-3-O-ß-D-glucopyranoside, and salidroside, respectively.

Alpha-glucosidase inhibitory constituents of Linaria kurdica subsp. eriocalyx.

Three known iridoid glycosides, antirrhide (1), antirrhinoside (2), and 5-O-beta-allosylantirrhinoside (3), and two known flavone glycosides, linariin (4"'-O-acetylpectolinarin) (4) and linarin (acacetin-7-O-beta-D-rutinoside) (5) were isolated from Linaria kurdica Boiss & Hohen. subsp. eriocalyx. The structures of the isolated compounds were established from spectroscopic evidence. Compounds 1-3 showed high inhibitory potential against alpha-glucosidase.

Triterpene glycosides from Astragalus icmadophilus.

Six cycloartane-type triterpene glycosides were isolated from Astragalus icmadophilus along with two known cycloartane-type glycosides, five known oleanane-type triterpene glycosides and one known flavonol glycoside. The structures of the six compounds were established as 3-O-[alpha-L-arabinopyranosyl-(1-->2)-O-3-acetoxy-alpha-L-arabinopyranosyl]-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-O-alpha-L-arabinopyranosyl-(1-->2)-O-beta-D-xylopyranosyl]-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxy cycloartane, 3-O-[alpha-L-arabinopyranosyl-(1-->2)-O-3,4-diacetoxy-alpha-L-arabinopyranosyl]-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane, 3-O-[alpha-L-arabinopyranosyl-(1-->2)-O-3-acetoxy-alpha-L-arabinopyranosyl]-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta,25-tetrahydroxy-20(R),24(S)-epoxycycloartane, 3-O-[alpha-L-arabinopyranosyl-(1-->2)-O-beta-D-xylopyranosyl]-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta,24alpha-tetrahydroxy-20(R),25-epoxycycloartane, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-O-alpha-L-arabinopyranosyl-(1-->2)-O-beta-D-xylopyranosyl]-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta,24alpha-tetrahydroxy-20(R),25-epoxycycloartane by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis. The first four compounds are cyclocanthogenin and cycloastragenol glycosides, whereas the last two are based on cyclocephalogenin as aglycone, more unusual in the plant kingdom, so far reported only from Astragalus spp.

Monoterpenoid glucoindole alkaloids and iridoids from Pterocephalus pinardii.

A new secondary metabolite, pterocephaline, along with the known cantleyoside, 7alpha-morroniside, 3beta,5alpha-tetrahydrodesoxycordifoline lactam, 5S-5-carboxyvincoside, sweroside, and loganin have been isolated from the aerial parts of P. pinardii (Dipsacaceae). Moreover, cantleyoside-methyl-hemiacetal and cantleyoside-dimethyl-acetal were obtained as seco-iridoid artifacts. The structures were elucidated by extensive spectroscopic methods including 1D-((1)H, (13)C and TOCSY) and 2D-NMR (DQF-COSY, HSQC and HMBC). Monoterpenoid glucoindole alkaloids were encountered for the first time in Dipsacaceae family.

Triterpene glycosides from Agrostemma gracilis.

Four triterpene saponins, agrostemmosides A-D were isolated from the methanol extract of Agrostemma gracilis. The structures of the compounds were determined as 3-O-beta-D-xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. To the best of our knowledge this is the first phytochemical report on A. gracilis, and echinocystic acid saponins were encountered for the first time in Caryophyllaceae family.

Triterpenoid saponins from Astragalus wiedemannianus Fischer.

Three cycloartane-type triterpene glycosides were isolated from Astragalus wiedemannianus together with eight known secondary metabolites namely cycloastragenol, cycloascauloside B, astragaloside IV, astragaloside VIII, brachyoside B, astragaloside II, astrachrysoside A, and astrasieversianin X. The structures were established mainly by a combination of 1D and 2D-NMR techniques as 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl]-25-O-beta-D-glucopyranosyl-20(R),24(S)-epoxy-3beta,6alpha,16beta,25-tetrahydroxycycloartane, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl]-6-O-beta-D-glucopyranosyl-24-O-alpha-(4'-O-acetoxy)-L-arabinopyranosyl-16-O-acetoxy-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl]-6-O-beta-D-glucopyranosyl-24-O-alpha-L-arabinopyranosyl-16-O-acetoxy-3beta,6alpha,16beta,24(S),25-pentahydroxycycloartane. To the best of our knowledge, the presence of an arabinose moiety on the acyclic side chain of cycloartanes is reported for the first time.

Triterpene glycosides from the roots of Astragalus flavescens.

Six new triterpene saponins, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-21-epi-kudzusapogenol A (1), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-21-epi-kudzusapogenol A (2), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-beta-D-glucopyranosyl-21-epi-kudzusapogenol A (3), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-beta-D-glucopyranosyl-21-epi-kudzusapogenol A (4), 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-alpha-L-arabinopyranosyl-21-epi-kudzusapogenol A (5), and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl-22-O-alpha-L-arabinopyranosyl-21-epi-kudzusapogenol A (6), were isolated from the roots of Astragalus flavescens, together with the known trajanoside B, azukisaponin V, and astragalosides IV, VII, and VIII. Their structures were established mainly by 2D NMR techniques and mass spectrometry.

Saponins from Styrax officinalis.

Three triterpene saponins named Styrax-saponin A-C (1-3) were found in pericarps of Styrax officinalis together with the deacylsaponin (4). Structural determinations were achieved using 1D-, 2D-NMR and mass spectrometry.