Pregnane Glycosides Research Articles

Sullivantosides A-F: Pregnane glycosides from Asclepias sullivantii L.

Phytochemical investigation of the above-ground biomass of Asclepias sullivantii L. (Asclepiadaceae) afforded six new pregnane glycosides, named sullivantosides A-F (1–6). The structures of 1–6 were elucidated through a variety of spectroscopic and spectrometric techniques (1D and 2D NMR; HRESIMS). To the best of our knowledge, this work represents the first phytochemical study of this species.

Russelioside B, a pregnane glycoside ameliorates hyperglycemia in streptozotocin induced diabetic rats by regulating key enzymes of glucose metabolism

An alternative strategy to treat diabetes mellitus is the use of various natural agents possessing hypoglycemic effect. Caralluma quadrangula has been used in Saudi traditional medicine in cases of thirst and hunger and for the treatment of diabetes. The present study was designed to evaluate the improving effect of russelioside B, a pregnane glycoside isolated from Caralluma quadrangula on glucose metabolism in the liver of streptozotocin-induced diabetic rats. Diabetes mellitus was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Experimental rats were administered russelioside B at a dose of 50 mg/kg body weight once a day for 30 days. The results showed that RB improved the fasting serum glucose level, glycated hemoglobin percent, serum insulin level and lipid profile. A significant improvement was observed upon the administration of russelioside B on the activities of the key enzymes of carbohydrate metabolism (glucokinase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and glycogen phosphorylase) in the liver of diabetic rats. Further, russelioside B administration to diabetic rats reverted gene expression of glucokinase, glucose-6-phosphatase, glycogen synthase and glycogen synthase kinase-3β to near normal levels. In conclusion, russelioside B possess antidiabetic and antihyperlipidemic effect in streptozotocin induced diabetic rats. Hence, administration of russelioside B may represent a potentially useful strategy for the management of diabetes.

Pregnane glycosides from the antidepressant active fraction of cultivated Cynanchum otophyllum

Based on the bioactive screening results, four new pregnane glycosides, namely cynanotophyllosides A–D (1–4) were isolated from the anti-depressant active fraction of cultivated Cynanchum otophyllum, along with thirteen known compounds (5–17). The new compounds were characterized as qingyangshengenin 3-O-β-D-glucopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (1), qingyangshengenin-3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-α-L-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (2), caudatin-3-O-β-D-glucopyranosyl-(1→4)-β-D-thevetopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-digitoxopyranoside (3) caudatin-3-O-β-D-glucopyranosyl -(1→4)-β-D-thevetopyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (4), by detailed spectroscopic analysis and acidic hydrolysis.

Two new pregnane glycosides from Reineckia carnea

Two new pregnane glycosides (1–2) and two known cholestane glycosides (3–4) were obtained from the whole plant Reineckia carnea. Their structures were characterized by physicochemical properties and spectroscopic methods, as (17, 20-S-trans)-5β-pregn-16-en-1β, 3β-ol-20-one 1-O-β-d-xylopyranosyl-(1→2)-α-l-rhamnopyranoside 3-O-α-l-rhamnopyranoside (1), (17, 20-S-trans)-pregna-5, 16-dien-3β-ol-20-one 3-O-β-d-glucopyranosyl-(1→2)-O-[β-d-xylopyranosyl-(1→3)]-O-β-d-glucopyranosyl-(1→4)-O-β-d-galactopyranoside (2), (22S)-cholest-1β, 3β, 16β, 22-tetraol 1-O-β-d-glucopyrannoside 16-O-β-d-glucopyrannoside (3), and (22S)-cholest-1β, 3β, 16β, 22-tetraol 1-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyrannoside 16-O-β-d-glucopyrannoside (4). In addition, their cytotoxic activity against human A549 tumor cells was evaluated by MTT method with 1–4 exhibited cytotoxicity with IC50 values of 87.7μmoll−1, 41.2μmoll−1, 46.6μmoll−1, and 49.5μmoll−1, respectively.

ChemInform Abstract: Steroidal and α‐Tocopherylhydroquinone Glycosides from Two Soft Corals Cladiella hirsuta and Sinularia nanolobata.

AbstractHirsutosterosides A (Ia) and B (Ib), cladophenol glycosides A (IIa) and B (IIb) and lobatasteroside A (III) together with six known compounds are isolated from the title corals.

Chemical constituents of Digitalis viridiflora

The genus Digitalis (Plantaginaceae) contains biennial or perennial species. It is represented by nine species in the flora of Turkey including D. viridiflora Lindley [1]. Phenylethanoid glycosides, cardiac glycosides, steroidal saponins and pregnane glycosides constitute the main group of secondary metabolites of the genus Digitalis [2, 3]. In continuation of our systematic survey on the chemical composition of Digitalis species growing in Turkey, we recently reported five phenylethanoid glycosides from D. viridiflora as the preliminary phytochemical research [4]. Further detailed chromatographic studies on the chemical constituents of the leaves of D. viridiflora led to the isolation of a new phenylethanoid glycoside named as digiviridifloroside (1) along with a known phenylethanoid glycoside (calceolarioside A), two flavonoids (scutellarein 7-O-β-D-glucopyranoside and hispidulin 7-O-β-D-glucopyranoside), two cleroindicins (cleroindicins B and F), a nucleoside (adenosine), as well as a mixture of β-D-glucopyranosyl-(1→6)-4-O-caffeoyl-α/β-glucopyranose and 3,4-dihydroxyphenylethanol which could be an artefact formed during isolation procedure. The structure of the new compound was established as 3,4-dihydroxy-β-phenylethoxy-6-O-(E)-feruloyl-β-D-glucopyranosyl-(1→6)-4-O-(E)-caffeoyl-β-D-glucopyranoside (1) based on extensive 1D- and 2D-NMR spectroscopy as well as MS. Digiviridifloroside (1) is the third example of rare phenylethanoid glycosides obtained from the genus Digitalis bearing two aromatic acyl units; the first two ones were reported from D. lanata [5].

A new pregnane glycoside from Gomphocarpus fruticosus growing in Egypt

Phytochemical investigation of Gomphocarpus fruticosus (L.) Ait. of Egyptian origin afforded the new pregnane glycoside lineolon-3-O-[β-D-oleandropyranosyl-(1–4)-β-D-cymaropyranosyl-(1–4)-β-D-cymaropyranoside], along with six known compounds. The structures of the isolated compounds were elucidated on the basis of extensive spectroscopic evidences derived from 1D, 2D NMR experiments, mass spectrometry and by comparing their physical and spectroscopic data to literature. These included the triterpenoids 3β-taraxerol, 3β-taraxerol acetate and betulinic acid, which are identified for the first time in G. fruticosus and the cardenolides uzarigenin, gomphoside and calotropin.

Nizwaside: a new anticancer pregnane glycoside from the sap of Desmidorchis flava.

The sap from the succulent Desmidorchis flava (N.E.Br) Meve and Liede yielded a new pregnane glycoside, named nizwaside whose structure was established using 1D and 2D NMR techniques as well as mass spectrometry (ESIMS). Nizwaside was tested for anticancer, DPPH antioxidant, urease enzyme inhibition, α-glucosidase enzyme inhibition and acetylcholinesterase inhibition activities. Interestingly, nizwaside showed significant anti-proliferative effects on MDA MB231 breast cancer cells with an IC(50) of 23.5 µg/ml. Moreover, nizwaside was more effective than Doxorubicin, a well-known clinical anticancer drug, in suppressing MDA MB231 cell proliferation even at concentrations lower than that of Doxorubicin (75 µg/ml nizwaside vs. 100 µg/ml Doxorubicin). On the other hand, nizwaside showed relatively weak antioxidant activity with 15 % inhibition.

Cytotoxicity of pregnane glycosides of Cynanchum otophyllum

Fourteen new pregnane glycosides, including nine caudatin glycosides (1–9), three qinyangshengenin glycosides (10–12), one kidjoranin glycosides (13) and one gagaminin glycosides (14), along with twelve known analogs (15–26) were isolated from roots of Cynanchum otophyllum Schneid. Their structures were deduced by detailed analysis of 1D and 2D NMR spectra, as well as HRESIMS. In this study, all pregnane glycosides obtained (1–26) were evaluated for their cytotoxic activities using three cancer cell lines (HepG2, Hela, U251). As results, except 6 and 10, other twenty-four pregnane glycosides showed cytotoxicities at different degrees against three cell lines.

Desmiflavasides A and B: Two new bioactive pregnane glycosides from the sap of Desmidorchis flava

The sap from the succulent, Desmidorchis flava (N.E.Br) Meve & Liede (Apocyanaceae), provided two new pregnane glycosides named desmiflavasides A (1) and B (2) whose structures were established from 1D and 2D NMR spectroscopic techniques and mass spectromentry (ESIMS) measurements. Desmiflavaside B (2) was tested for anticancer activity and induced a 27.4% and 33.1% growth inhibition of the breast cancer cell line (MDA MB231) at a concentration of 75μg/ml and 100μg/ml, respectively. Desmiflavasides A (1) and B (2) were additionally evaluated for: DPPH antioxidant activity, urease enzyme inhibition as well as for xanthine oxidase enzyme, α-glucosidase enzyme and acetylcholinesterase inhibition activities. They displayed weak antioxidant and urease enzyme inhibition activities with 15% inhibition.

New pregnane glycosides from Gymnema sylvestre.

Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1–4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity.

New pregnane glycoside derivative from Caralluma retrospiciens (Ehrenb)

Retrospinoside (1) is a new polyoxy pregnane glycoside which was isolated and characterised from the aerial parts of Caralluma retrospiciens (Ehrenb.) N. E. Br., family Apocynaceae. The structure was established as 3-O-[β-D-glucopyranosyl-(1 → 4)-β-D-(3-O-methyl-6-desoxygalactopyranosy)]-14,15,20-trihydroxy-4β-pregnane. Its structural elucidation was performed through extensive spectroscopic measurements including 1D- and 2D-NMR, and HRMS, in addition to chemical methods.

Three-step isolation of a new pregnane from Cynanchum marnieranum Rauh (Apocynaceae)

While there is a rich bibliography concerning the phytochemistry of Asian leaf-bearing Cynanchum species, quite limited work has been done about leafless stem succulent Cynanchum species endemic to Madagascar [1]. Hence, we decided to investigate several Cynanchum species, focusing on Cynanchum marnieranum Rauh from the South of Madagascar. The ethanol extract from the dried stems was submitted to liquid/liquid partition followed by solid phase extraction (SPE) of the non-polar phase. The most interesting fraction was further separated by centrifugal partition chromatography (CPC), choosing the quaternary solvent system cyclohexane: ethyl acetate: methanol: water (6:5:6:5). This led to the isolation of a new pregnane glycoside, which was identified by combination of HR-ESI-TOF-MS and 1D and 2D NMR data as 12,20 dibenzoyl-(20S) – pregn-6-ene-3β,5α,8β,12β,14β,17β,20β -heptol 3-O-β-D-oleandropyranosyl (1→4)-β-D-cymaropyranoside, named marnieranoside A (figure 1). The novelty of this structure is based on the double substitution with benzoyl moieties fixed on a Δ6,7 pregnane structure which occurs for the first time in the genus Cynanchum. Indeed, only Δ5,6 pregnanes have been reported from Cynanchum species until now [2]. This CPC fractionation led also to other Δ6,7 pregnane glycosides according to the 1 H NMR data, which could indicate a specific Δ6,7 pregnane biosynthetic pathway in Cynanchum marnieranum.

New antimicrobial pregnane glycosides from the stem of Ecdysanthera rosea

Phytochemical investigation on the stem of Ecdysanthera rosea led to the isolation of eight new C-21 pregnane glycoside ecdysosides A–H (1–8), together with one known pregnane glycoside ecdysantheroside A (9). Their structures were elucidated based on extensive spectroscopic data (MS, IR, 1D and 2D NMR) analysis, as well as comparison with the reported literature data. Antimicrobial activities of all the compounds were evaluated against bacteria and yeasts. Compounds 1, 9, 3 and 5 exhibited moderate antibacterial activities against respective Enterococcus faecalis and Providensia smartii, with MIC value of 12.5μg/mL. Compound 8 showed significant anti-yeast activity against Cryptococcus neoformans with MIC value of 12.5μg/mL.

Histopathological effects and immunolocalization of periplocoside NW from Periploca sepium Bunge on the midgut epithelium of Mythimna separata Walker larvae

Periplocoside NW (PSNW) with pregnane glycoside skeleton is a novel insecticidal compound isolated from the root bark of Periploca sepium Bunge. This compound has a potent stomach poisoning activity against several insect pests. In this study, we observed the intoxication symptoms, investigated the histopathological effects and carried out immuno-electron microscopic localization of PSNW on the midgut epithelium of oriental armyworm Mythimna separata Walker larvae for better understanding its action mechanism against insects. Ultrastructural observations showed that cell damages caused by PSNW in the midgut of M. separata larvae are related to the degeneration of brush border microvilli. The dissolution of cytoskeletal structures in the interior and on the surface of microvilli was responsible for the decrease in size and eventual disappearance of microvilli when bubbles of cytoplasmic substances protrude into the midgut lumen of M. separata, thus resulting in cell death. The immuno-electron microscopic localization research showed that gold particle appeared on the microvilli layer of the midgut of M. separate larvae firstly. The density of gold particle gradually added with the time, and finally microvilli layer was destructed severely. Meantime, the gold particles were also presented to the intracellular organelle membrane and the organelles also were destructed. Therefore, we proposed that this membrane system on insect midgut epithelium cells is the initial acting site of PSNW against insects.

New steroidal glycosides from the rhizome of Anemarrhena asphodeloides

Two new steroidal saponins, timosaponin X (1) and timosaponin Y (2), and one new pregnane glycoside, timopregnane B (3), were isolated from the rhizomes of Anemarrhena asphodeloides, as well as three known compounds 25S-timosaponin BII (4), protodesgalactotigonin (5), and timosaponin BII-a (6) isolated from this plant for the first time. By the detailed analysis of 1D, 2D NMR, MS spectra, and chemical evidences, the structures of new compounds were elucidated as 26-O-β-d-glucopyranosyl-(25S)-5β-22-methoxy-furost-3β,26-diol 3-O-β-d-glucopyranosyl-(1 → 2)-α-l-arabinopyranoside (1), 5β-pseudo-spirost-3β,15α,23α-triol 3-O-β-d-glucopyranosyl-(1 → 2)-β-d-galactopyranoside (2), (5β,17α)-Δ16(17)-20-one-pregn-2β,3β-diol 3-O-β-d-glucopyranosyl-(1 → 2)-β-d-galactopyranoside (3).

A new pregnane glycoside from Rubus phoenicolasius and its antiproliferative activity

Chemical investigations of the whole plant ethanol extract of Rubus phoenicolasius led to the isolation and identification of a new pregnane glycoside, 3-O-β-glucopyranosyl-3β,15β-dihydroxypregn-5-en-20-one (1), along with other nine known compounds (2–10). All the isolates were reported from this plant for the first time. The structure of compound 1 was determined by detailed analysis of its spectral data including 1D and 2D NMR. In vitro anti-proliferative activities of compounds 1–3 on MCF-7 and NCI-H460 tumour cell lines were evaluated, and compound 1 was active against the two cell lines with IC50 values of 15.6 and 13.5 μM, respectively.

ChemInform Abstract: Two New Pregnane Glycosides from the Roots of Cynanchum atratum

Abstractisolation and structure elucidation of two new pregnane glycosides, cynatraosides A (I) and B (II), along with six known steroids

A review on ethnobotany, phytochemistry and pharmacology of plant genus Caralluma R. Br.

Caralluma is a xerophytic genus used as traditional medicine for the treatment of diabetes, inflammation, leprosy, obesity and rheumatism. Objectives of this review are to establish a relationship between traditional uses and scientific studies by critically evaluating the available fragmented literature on ethnobotany, pharmacology, phytochemistry and toxicology of genus Caralluma. Ethnomedical uses of Caralluma have been recorded from various countries such as China, India, Iran and Pakistan for six major classes of diseases including diabetes and gastrointestinal disorders. This review indicated the efficacy of genus Caralluma in several in vitro and in vivo pharmacological properties such as antimicrobial, antioxidant and anticancer activity. These bioactivity might be due to the presence of certain classes of compounds in genus Caralluma including pregnane glycosides, flavonoid glycosides and flavones. Traditional uses and scientific evaluation of Caralluma indicates that it is one of the most widely used genus in some parts of the world. Further studies on the structural activity relationship of some of the isolated compound may improve their biological potency as well as scientific exploitation of traditional uses of the genus.

Cover Picture: Synthesis of the Aglycone of the Argelosides: Antiproliferative 14,15-seco-Pregnane Glycosides (Asian J. Org. Chem. 3/2014)

Highly oxygenated steroidal derivatives are important targets in biology and chemistry. In their Communication on page 264 ff., Minoru Tamiya and co-workers accomplished the synthesis of the aglycon of the argelosides, a highly-oxygenated seco-pregnane with cage-like D, E, and F rings, through the three oxidative operations: 1) Sharpless asymmetric dihydroxylation, 2) Baeyer-Villiger oxidation, and 3) Wacker oxidation. Despite the rather simple strategy, the major challenge lay in handling the easy-to-aromatize structure in the intermediate and target molecules.