New Steroidal Glycosides from Rhizomes of Clintonia udensis

A total of 10 steroidal glycosides, together with three new spirostanol glycosides (6–8), a new furostanol glycoside (9), and a new cholestane glycoside (10), were isolated from the rhizomes of Clintonia udensis (Liliaceae). The structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including 2-D nuclear magnetic resonance (NMR) data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. The isolated glycosides were evaluated for their cytotoxic activity against HL-60 leukemia cells. Spirostanol glycosides 1 and 2, and furostanol glycoside 4 showed cytotoxic activity with IC₅₀ values of 3.2±0.02, 2.2±0.12, and 2.2±0.06 μg/ml, respectively. Neither the spirostanol and furostanol saponins with a hydroxy group at C-1 (6 and 9) and C-12 (7 and 8) nor cholestane glycosides (5 and 10) exhibited apparent cytotoxic activity at a sample concentration of 10 μg/ml.     

Six New Polyhydroxysteroidal Glycosides,Anthenosides S1 – S6, from the Starfish Anthenea sibogae

Six new polyhydroxysteroidal glycosides, anthenosides S1  –  S6 ( 1  –  6 ), along with a mixture of two previously known related glycosides, 7 and 8 , were isolated from the methanolic extract of the starfish Anthenea sibogae. The structures of 1  –  6 were established by NMR and HR‐ESI‐MS techniques as well as by chemical transformations. All new compounds have a 5α‐cholest‐8(14)‐ene‐3α,6β,7β,16α‐tetrahydroxysteroidal nucleus and differ from majority of starfish glycosides in positions of carbohydrate moieties at C(7) and C(16) ( 1  –  4 , 6 ) or only at C(16) ( 5 ). The 4‐O‐methyl‐β‐d ‐glucopyranose residue ( 2 ) and Δ²⁴‐cholestane side chain ( 3 ) have not been found earlier in the starfish steroidal glycosides. The mixture of 7 and 8 slightly inhibited the proliferation of human breast cancer T‐47D cells and decreased the colony size in the colony formation assay.     

Synthesis of cholestane saponins as mimics of OSW-1 and their cytotoxic activities

To fulfill the structure-activity relationship (SAR) of OSW-1, and aim at finding the simplest structural part while maintaining most of the biological activities, six cholestane saponins were synthesized by introducing OSW-1 disaccharide (2-O-4-methoxybenzoyl-β-d-xylopyranosyl-(1→3)-2-O-acetyl-α-l-arabinopyranosyl) and its 1→4-linked analogue to the 7-hydroxy or 16-hydroxy of steroidal sapogenins. Cytotoxic activities of the products were tested. Compounds 1 and 3 exhibited potent cytotoxicities against five types of human tumor cells, with minimum IC₅₀ of 2.0 and 75 nM, respectively. And due to its high activity and easy accessibility compound 1 could be a potential candidate for new anti-tumor agents.     

New steroidal glycosides from rhizomes of Clintonia udensis

A total of 10 steroidal glycosides, together with three new spirostanol glycosides (6-8), a new furostanol glycoside (9), and a new cholestane glycoside (10), were isolated from the rhizomes of Clintonia udensis (Liliaceae). The structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including 2-D nuclear magnetic resonance (NMR) data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. The isolated glycosides were evaluated for their cytotoxic activity against HL-60 leukemia cells. Spirostanol glycosides 1 and 2, and furostanol glycoside 4 showed cytotoxic activity with IC(50) values of 3.2+/-0.02, 2.2+/-0.12, and 2.2+/-0.06 microg/ml, respectively. Neither the spirostanol and furostanol saponins with a hydroxy group at C-1 (6 and 9) and C-12 (7 and 8) nor cholestane glycosides (5 and 10) exhibited apparent cytotoxic activity at a sample concentration of 10 microg/ml.     

Steroidal saponins from Yucca gloriosa L. rhizomes: LC-MS profiling, isolation and quantitative determination

The occurrence of steroidal saponins in the rhizomes of Yucca gloriosa has been detected by LC-MS. On the basis of the LC-MS analysis, five steroidal glycosides, including three spirostane, one furostane and one cholestane glycosides, along with seven known compounds have been isolated and characterized by ESI-MS and by the extensive use of 1D- and 2D-NMR experiments. Quantitative analysis of the steroidal glycosides in Y. gloriosa rhizomes was performed by an LC-MS method validated according to European Medicines Agency (EMEA) guidelines. The dried BuOH extract obtained from rhizomes contains more than 25% w/w of glycosides, thus Y. gloriosa rhizomes can be considered a rich source of steroidal glycosides.     

Steroidal saponins from the aerial parts of Tribulus alatus Del

Six steroidal glycosides (1-6) were isolated from the aerial parts of Tribulus alatus Del. (Zygophyllaceae), together with one known cholestane, one spirostane, and six flavonol glycosides. Among them, 1 and 2 possess a furostane-type aglycone, 3 and 6 a cholestane structure, and 4 and 5 a spirostane skeleton. Their structural elucidation was accomplished by extensive spectroscopic methods including 1D ((1)H, (13)C, (13)C DEPT, TOCSY, ROESY) and 2D NMR experiments (DQF-COSY, HSQC, HMBC) as well as ESI-MS analysis.     

晚香玉球茎中的一个新胆甾烷类配糖体

从晚香玉(Polianthes tuberosa L.)球茎中分离到3个胆甾烷类配糖体。经波谱分析鉴定,其中1个为新的胆甾烷类配糖体,即(22S)—胆甾烷-5-烯-1β,3β,16β,22,25-五醇1—O—β-D-葡萄毗喃糖基—16—O-β-D芹菜呋喃糖苷。     

Iridoid Glycosides from Tabebuia avellanedae

Five novel iridoid glycosides, avellanedaesides A‐E ( 1  –  5 ) were isolated from the H₂O extract of Tabebuia avellanedae. Their structures were determined on the basis of NMR and MS analysis. Isolated compounds suppressed inflammatory cytokine, tumor‐necrosis factor‐α and interleukin‐1β production in cultured human myeloma THP‐1 cells co‐stimulated with lipopolysaccharide (LPS). In addition, the study revealed iridoid glycosides inhibited the activity of cytochrome CYP3A4 enzyme.     

Cloning, expression, and characterization of an aldehyde dehydrogenase from Escherichia coli K-12 that utilizes 3-Hydroxypropionaldehyde as a substrate

For efficient production of isoflavone aglycones from soybean isoflavones, we isolated three novel types of β-glucosidase (BGL1, BGL3, and BGL5) from the filamentous fungi Aspergillus oryzae. Three enzymes were independently displayed on the cell surface of a yeast Saccharomyces cerevisiae as a fusion protein with α-agglutinin. Three β-glucosidase-displaying yeast strains hydrolyzed isoflavone glycosides efficiently but exhibited different substrate specificities. Among these β-glucosidases, BGL1 exhibited the highest activity and also broad substrate specificity to isoflavone glycosides. Although glucose released from isoflavone glycosides are generally known to inhibit β-glucosidase, the residual ratio of isoflavone glycosides in the reaction mixture with BGL1-displaying yeast strain (Sc-BGL1) reached approximately 6.2%, and the glucose concentration in the reaction mixture was maintained at lower level. This result indicated that Sc-BGL1 assimilated the glucose before they inhibited the hydrolysis reaction, and efficient production of isoflavone aglycones was achieved by engineered yeast cells displaying β-glucosidase.     

Isoflavone glycosides from Derris scandens

Five isoflavone glycosides, named derriscandenosides A–E (1–5), were isolated from the stems of Derris scandens, together with ten known compounds comprising one isoflavone, two benzoic acid derivatives, three glucosyl isoflavones and four rhamnosyl-(1→6)-glucosyl isoflavones. The structures of the glycosides were assigned on the basis of spectroscopic data, especially of the acetate derivatives. Three known rhamnosyl-(1→6)-glucosyl isoflavones isolated from a crude fraction were retested for hypotensive activity with varying results.     

Chemical constituents of the plants of the genus <Emphasis Type="Italic">Cleistanthus</Emphasis> and their biological activity

Chemical examinations of Cleistanthus collinus Roxb., a poisonous tree from India, and Cleistanthus patulus Muell. Arg. have resulted in isolation of a number of arylnaphthalide lignans and their glycosides as well as some furofuranoid lignans. While Cleistanthus gracilis Hook. f. from Thailand afforded an unusual glucoside of 2-β-hydroxy-8-azabicyclo-(5,0,2)-4β, 9β-epoxynona-5,7-diene, C. schlechteri from South Africa was the first reported source of the pimarane diterpenes. Cleistanthin A and cleistanthin B, diphyllin glycosides isolated from C. collinus were reported to exhibit cytotoxicity on several cancer cell lines. Cleistanthin A was found to cause DNA strand breaks and induce apoptosis in cultured cells while cleistanthin B caused G1 arrest and induced apoptosis in mammalian cells.     

Anti-Inflammatory Activities of Monoterpene and Sesquiterpene Glycosides from the Aqueous Extract of Artemisia annua L.

Artemisia annua L. is a Chinese medicinal herb, but the origin of its pharmacological properties, including its anti-inflammatory activity, remain unknown. In this study, five new monoterpene glycosides ( 1 – 5 ) and two new sesquiterpene glycosides ( 6 and 7 ) were isolated from the aqueous extract of the aerial parts of A. annua. The structures of these glycosides were determined using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, electronic circular dichroism calculations, and chemical hydrolysis methods. The anti-inflammatory activities of the isolated compounds were evaluated by down-regulating interleukin-6 (IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Notably, all the new compounds significantly inhibited the expression of IL-6 in a dose-dependent manner.     

Interconverting flavanone glucosides and other phenolic compounds in Lippia salviaefolia Cham. ethanol extracts

Four interconverting flavanone glycosides [(2R)- and (2S)-3′,4′,5,6-tetrahydroxyflavanone 7-O-β-d-glucopyranoside, and (2R)- and (2S)-3′,4′,5,8-tetrahydroxyflavanone 7-O-β-d-glucopyranoside], in addition to eight known flavonoids [naringenin, asebogenin, sakuranetin, 6-hydroxyluteolin 7-O-β-d-glucoside, (2R)- and (2S)-eriodictyol 7-O-β-d-glucopyranoside, aromadendrin and phloretin], three phenylpropanoid glycosides [forsythoside B, alyssonoside and verbascoside] and the epoxylignan lariciresinol 4′-O-β-d-glucopyranoside were isolated and identified in the EtOH extract of the aerial parts of Lippia salviaefolia Cham. The phytochemical study herein was guided by preliminary antioxidant tests, namely, β-carotene protection and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity. The crude extracts, their active fractions and the isolated compounds were assayed against intracellular reactive oxygen species (ROS) and human embryonic kidney HEK-293 and human melanoma M14 cancer cell growth. Aromadendrin and phloretin were able to counteract elevation of ROS induced by the oxidant t-butylhydroperoxide (t-BOOH) in HEK-293 cells, whereas phloretin strongly protected HEK-293 cells from ROS damage at 1 μM. Additionally, phloretin exhibited a significant growth inhibitory effect at 20–40 μM in both HEK-293 and M14 cells and induced a concentration dependent apoptosis at 20 μM in M14 cells, suggesting a selective action towards malignant cells. Due to their equilibria, the four interconverting flavanone glycosides were studied using 1D and 2D NMR, HPLC–CD–PDA and HRMS analyses.     

A Comparative Study of the Hemolytic and Cytotoxic Activities of Triterpenoids Isolated from Ginseng and Sea Cucumbers

Specific features of cytotoxic (against tumor cells), hemolytic, and liposomal (effect on permeability) activities of triterpenoids isolated from sea cucumbers and ginseng roots were studied. It was shown that oleanolic acid, protopanaxatriol, and protopanaxadiol at 5 to 20 g/ml inhibited the growth of tumor cells, while at doses up to 100 g/ml, they did not induce hemolysis or changes in liposome permeability. Monoglucosides of protopanaxadiol, Rh ₂, Rg ₃, and substance K exerted moderate cytotoxic and membrane activities. The membrane sensitivity to these glucosides was inversely proportional to the membrane content of cholesterol. The cytotoxicity of the protopanaxadiol-active glycosides increased with a decrease of pH of the medium. All studied glycosides did not affect the cell and model lipid membranes. The activity of the oleanolic acid glycoside, ginsenoside Z-R1, depended to a great extent on the pH of the medium. The decrease of pH from 7.4 to 5.6 increased the membranolytic activities by more than one order of magnitude. Glycosides from sea cucumbers, echinosides A and B, holothurins A and B, holotoxin ₁, and cucumarioside G ₁, had very high cytotoxic and liposomal activities. Addition of cholesterol to cell membranes enhanced the cytotoxic effects of these glycosides. The ginsenosides with two carbohydrate moieties (bisdesmosides), as well as all the panaxatriol glycosides we studied did not exhibit cytotoxic activities against tumor cells or alter the permeability of model lipid and lipid-sterol membranes. The triterpenoids studied were classified into four categories in accordance with their membranotropic activities. A possible protective role of these glycosides in the organism-producent is discussed.     

Synthesis of steroidal glycosides bearing the disaccharide moiety of OSW-1 and their antitumor activities

Nine glycosides bearing the disaccharide of OSW-1, namely 2-O-(4-methoxybenzoyl)-beta-D-xylopyranosyl-(1-->3)-2-O-acetyl-alpha-L-arabinopyranosides, were synthesized, and their antitumor activities were tested.     

Anticancer saponin OSW-1 is a novel class of selective Golgi stress inducer

OSW-1 is a plant-derived natural product proposed to selectively kill cancer cells by binding to members of the oxysterol binding protein family, thereby disrupting lipid/sterol homeostasis. However, how these protein-ligand interactions mediate cell death signaling has remained elusive. Here, we discovered that OSW-1 selectively activates the Golgi stress response leading to apoptosis, providing a mechanistic basis for the anticancer activity of OSW-1.     

Sulfated Purine Alkaloid Glycosides from the Pupal Case Built by the Bruchid Beetle Bruchidius dorsalis Inside the Seed of Gleditsia japonica

Three new sulfated isoguanine alkaloid glycosides, designated as saikachinoside A monosulfate ( 1 ), saikachinoside A disulfate ( 2 ), and locustoside B disulfate ( 3 ), have been isolated from the pupal case of the wild bruchid seed beetle Bruchidius dorsalis (Chrysomelidae, Bruchinae) infesting the seed of Gleditsia japonica Miq . (Fabaceae). Their structures were determined by spectroscopic methods and the inhibitory activity of 2 and 3 against acid phosphatase was evaluated.     

Studies on the production of daunomycinonederived glycosides and related metabolites inStreptomyces coeruleorubidus andStreptomyces peucetius

Strains ofStreptomyces coeruleorubiduě ISP 5145,JA 10092 and 39–146, differing mutually in antibiotic activity, were found to produce identical spectrum of metabolites (at least nine antibiotically active glycosides, 13-dihydrodaunomycinone, ε-rhodomycinone and a larger number of unidentified compounds); only trace quantities of daunomycin and daunomycinone could be detected. A fraction of glycosides with a higher R_f (0.4–0.7), isolated from strain 39–146, could be transformed to daunomycin by mild hydrolysis and to daunomycinone by total hydrolysis.Streptomyces peucetius IMI 101 335 differed fromStreptomyces coeruleorubidus in an increased production of ε-rhodomycinone and a lower content of glycosides; the zone of daunomycin was most pronounced among the glycoside spots.Streptomyces coeruleorubidus 39-146 exhibited the highest activity in a medium containing 3.5% soluble starch, 3.0% soybean meal, 0.3% NaCl and 0.3% CaCo₃; glucose was a more useful carbon source for the remaining strains The activity ofStreptomyces coeruleorubidus was inhibited by 1-propanol, Na-propionate,5,5-diethylbarbiturate and bacitracin. Ferrous sulphate stimulated the production of glycosides only in strain JA 10092, decreasing simultaneously the production of aglycones.