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Fitoterapia Jul 2023Twenty compounds comprising four pregnane steroids (2-4 & 20) and 16 pregnane glycosides (1 & 5-19) have been obtained from the ethanol extract of the roots of a Dai...
Twenty compounds comprising four pregnane steroids (2-4 & 20) and 16 pregnane glycosides (1 & 5-19) have been obtained from the ethanol extract of the roots of a Dai ethnological herb, Marsdenia tenacissima. Their structures were characterized on the basis of comprehensive spectroscopic analyses with 17 ones (1-17) being reported for the first time, including the rare cases (2 & 3) of free C steroids with 17α-acetyl substitution, compounds 4-7 bearing an unusual 14α-OH, and the first examples with simultaneous 14α-OH/17α-acetyl substitution (7) and glycosylation at C-12 position (10 & 11). An empirical rule for the identification of C-17 configuration, in C steroids incorporating the marsdenin constitution structure, was also proposed. All the isolates, along with an array of previously reported analogues in our compound library, were screened for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and six compounds exhibited moderate MDR reversal activity with reversal folds ranging from 1.92 to 4.44.
Topics: Marsdenia; Molecular Structure; Steroids; Pregnanes; Glycosides; Drug Resistance, Multiple
PubMed: 37247696
DOI: 10.1016/j.fitote.2023.105551 -
Natural Product Research Nov 2021Two new pregnane alkaloids, (20)-20-cinnamoylamino-3-dimethylamino-5-en-pregnane () and (20)-20-cinnamoylamino-3-dimethylamino-pregnane (), and four known alkaloids...
Two new pregnane alkaloids, (20)-20-cinnamoylamino-3-dimethylamino-5-en-pregnane () and (20)-20-cinnamoylamino-3-dimethylamino-pregnane (), and four known alkaloids (+)-(20)-20-(dimethylamino)-3-(3'-isopropyl)-lactam-5-pregn-2-en-4-one (), axillaridine A (), pachysamine M () and 20-dimethylamino-16-hydroxy-3-senecioylamino-pregn-5-ene () were obtained from the whole herb of Sieb. et Zucc. Their structures were determined by various spectral techniques and computed electronic circular dichroism (ECD) data. Compounds were tested for cytotoxicity against three human tumor cell lines and a human umbilical vein endothelial cell (HUVEC) line. Compound exhibited moderate cytotoxicity against MCF-7, U251 and A549 cells with IC values of 15.01 ± 0.47 μM, 20.13 ± 1.34 μM and 20.04 ± 1.16 μM, respectively; compounds showed weak cytotoxic activity against three tumor cells.
Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Humans; Pachysandra; Plant Extracts; Pregnanes
PubMed: 32208773
DOI: 10.1080/14786419.2020.1744143 -
Steroids Nov 2015In plants androstanes, estranes, pregnanes and corticoids have been described. Sometimes 17β-estradiol, androsterone, testosterone or progesterone were summarized as... (Review)
Review
In plants androstanes, estranes, pregnanes and corticoids have been described. Sometimes 17β-estradiol, androsterone, testosterone or progesterone were summarized as sex hormones. These steroids influence plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. First reports on the effect of applicated substances and of their endogenous occurrence date from the early twenties of the last century. This caused later on doubts on the identity of the compounds. Best investigated is the effect of progesterone. Main steps of the progesterone biosynthetic pathway have been analyzed in Digitalis. Cholesterol-side-chain-cleavage, pregnenolone and progesterone formation as well as the stereospecific reduction of progesterone are described and the corresponding enzymes are presented. Biosynthesis of androstanes, estranes and corticoids is discussed. Possible progesterone receptors and physiological reactions on progesterone application are reviewed.
Topics: Plant Development; Plant Growth Regulators; Plant Physiological Phenomena; Plants; Pregnanes; Progesterone
PubMed: 26282543
DOI: 10.1016/j.steroids.2015.08.007 -
Molecules (Basel, Switzerland) Mar 2023The ethnobotanical plant has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed...
The ethnobotanical plant has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (-), were isolated from cultivated dried stems of the medicinal plant in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A () featured an unusual 8,14--pregnane skeleton. Compounds , , and showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC values of 37.5, 38.8, and 42.8 μM (L-NMMA was used as a positive control, IC 39.3 μM), respectively. This study puts the knowledge of the chemical profile of the botanical plant one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.
Topics: Humans; Plants, Medicinal; Marsdenia; China; Pregnanes; Glycosides
PubMed: 36985677
DOI: 10.3390/molecules28062705 -
Natural Product Research Jul 2021Two new pregnane glycosides, gyminosides A and B ( and ) and three known, tinctoroside B (), tinctoroside C (), and gymnepregoside F () were isolated from the leaves of...
Two new pregnane glycosides, gyminosides A and B ( and ) and three known, tinctoroside B (), tinctoroside C (), and gymnepregoside F () were isolated from the leaves of (Lour.) Decne. Their structures were elucidated by physical and chemical methods and comparing with those reported in the literature. All these compounds were evaluated for -glucosidase assay. Compound exhibited the most anti -glucosidase activity with inhibitory percentage of 63.7 ± 3.9% at the concentration of 200 μM. Compounds - showed moderate anti -glucosidase activity with inhibitory percentage ranging from 40.0 to 52.1%.
Topics: Carbon-13 Magnetic Resonance Spectroscopy; Glycoside Hydrolase Inhibitors; Glycosides; Gymnema; Plant Leaves; Pregnanes; Proton Magnetic Resonance Spectroscopy; alpha-Glucosidases
PubMed: 31507227
DOI: 10.1080/14786419.2019.1663517 -
Journal of Natural Medicines Jan 2019Seven new pregnane glycosides (1-7) and eight known compounds (8-15) were isolated from the bark of Marsdenia cundurango (Asclepiadaceae). The structures of 1-7 were...
Seven new pregnane glycosides (1-7) and eight known compounds (8-15) were isolated from the bark of Marsdenia cundurango (Asclepiadaceae). The structures of 1-7 were determined by spectroscopic analysis, including two-dimension NMR spectroscopy, chemical transformations, and chromatographic analysis of the hydrolyzed products. The isolated compounds 1-15 were evaluated for their cytotoxic activity against HL-60 human leukemia cells, A549 human lung adenocarcinoma cells, and TIG-3 normal human lung cells, including apoptosis-inducing activity of a representative pregnane glycoside in HL-60 cells.
Topics: Cytotoxins; Glycosides; HL-60 Cells; Humans; Marsdenia; Plant Bark; Pregnanes
PubMed: 30251034
DOI: 10.1007/s11418-018-1248-0 -
Pharmacology 2022The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated...
INTRODUCTION
The present study deals with the synthesis of pregnane-oximino-amino-alkyl-ethers and their evaluation for antidiabetic and anti-dyslipidemic activities in validated animal and cell culture models.
METHODS
The effect on glucose tolerance was measured in sucrose-loaded rats; antidiabetic activity was evaluated in streptozotocin (STZ)-induced diabetic rats and genetically diabetic db/db mice; the anti-dyslipidemic effect was characterized in high-fructose, high-fat diet (HFD)-fed dyslipidemic hamsters. The effect on glucose production and glucose utilization was analyzed in HepG2 liver and L6 skeletal muscle cells, respectively.
RESULTS
From the synthesized molecules, pregnane-oximino-amino-alkyl-ether (compound 14b) improved glucose clearance in sucrose-loaded rats and exerted antihyperglycemic activity on STZ-induced diabetic rats. Further evaluation in genetically diabetic db/db mice showed temporal decrease in blood glucose, and improvement in glucose tolerance and lipid parameters, associated with mild improvement in the serum insulin level. Moreover, compound 14b treatment displayed an anti-dyslipidemic effect characterized by significant improvement in altered lipid parameters of the high-fructose, HFD-fed dyslipidemic hamster model. In vitro analysis in the cellular system suggested that compound 14b decreased glucose production in liver cells and stimulated glucose utilization in skeletal muscle cells. These beneficial effects of compound 14b were associated with the activation of the G-protein-coupled bile acid receptor TGR5.
CONCLUSION
Compound 14b exhibits antidiabetic and anti-dyslipidemic activities through activating the TGR5 receptor system and can be developed as a lead for the management of type II diabetes and related metabolic complications.
Topics: Animals; Blood Glucose; Cell Line; Cricetinae; Diabetes Mellitus, Experimental; Dyslipidemias; Fenofibrate; Glucose Transporter Type 4; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Male; Mice; Muscle, Skeletal; Pregnanes; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled
PubMed: 34814141
DOI: 10.1159/000519721 -
Molecules (Basel, Switzerland) May 2020A concise synthesis of (16,20)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route...
A concise synthesis of (16,20)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization with EtSiH/TFA or EtSiH/Bi(TfO). Alternately, the lactone was converted first to the oxo-acid, which was then subjected to the microwave-assisted reductive amination. -Alkyl derivatives were also obtained in a similar way.
Topics: Cyclization; Lactones; Oxidation-Reduction; Pregnanes
PubMed: 32443910
DOI: 10.3390/molecules25102377 -
British Journal of Pharmacology Aug 2022N-methyl-D-aspartate receptors (NMDARs) play a critical role in synaptic plasticity, and mutations in human genes encoding NMDAR subunits have been described in...
BACKGROUND AND PURPOSE
N-methyl-D-aspartate receptors (NMDARs) play a critical role in synaptic plasticity, and mutations in human genes encoding NMDAR subunits have been described in individuals with various neuropsychiatric disorders. Compounds with a positive allosteric effect are thought to compensate for reduced receptor function.
EXPERIMENTAL APPROACH
We have used whole-cell patch-clamp electrophysiology on recombinant rat NMDARs and human variants found in individuals with neuropsychiatric disorders, in combination with in silico modelling, to explore the site of action of novel epipregnanolone-based NMDAR modulators.
KEY RESULTS
Analysis of the action of 4-(20-oxo-5β-pregnan-3β-yl) butanoic acid (EPA-But) at the NMDAR indicates that the effect of this steroid with a "bent" structure is different from that of cholesterol and oxysterols and shares a disuse-dependent mechanism of NMDAR potentiation with the "planar" steroid 20-oxo-pregn-5-en-3β-yl sulfate (PE-S). The potentiating effects of EPA-But and PE-S are additive. Alanine scan mutagenesis identified residues that reduce the potentiating effect of EPA-But. No correlation was found between the effects of EPA-But and PE-S at mutated receptors that were less sensitive to either steroid. The relative degree of potentiation induced by the two steroids also differed in human NMDARs carrying rare variants of hGluN1 or hGluN2B subunits found in individuals with neuropsychiatric disorders, including intellectual disability, epilepsy, developmental delay, and autism spectrum disorder.
CONCLUSION AND IMPLICATIONS
Our results show novel sites of action for pregnanolones at the NMDAR and provide an opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with glutamatergic system hypofunction.
Topics: Animals; Autism Spectrum Disorder; Mutation; Pregnanes; Rats; Receptors, N-Methyl-D-Aspartate; Steroids
PubMed: 35318645
DOI: 10.1111/bph.15841 -
Phytochemistry Dec 2019Five undescribed C pregnane glycosides, epigycosides D-H, together with four known analogues, two lignans, and a flavonoid have been isolated from the stems of Epigynum...
Five undescribed C pregnane glycosides, epigycosides D-H, together with four known analogues, two lignans, and a flavonoid have been isolated from the stems of Epigynum cochinchinensis. The structures of pregnane glycosides were elucidated using spectroscopic techniques and acid hydrolysis. The in vitro immunological activities were assessed against Con A-stimulated proliferation of mice splenocytes. The C pregnane glycosides showed immunosuppressive activity in a concentration-dependent manner. Moreover, epigycoside E exhibited a potent immunosuppressive effect, and the IC value on Con A-stimulated mice splenocytes was 22.1 ± 6.4 μM. Epigycoside E also caused G/G arrest, and inhibited TNF-α and IL-2 production.
Topics: Animals; Apocynaceae; Cell Cycle; Cell Proliferation; Concanavalin A; Crystallography, X-Ray; Dose-Response Relationship, Drug; Glycosides; Immunosuppressive Agents; Male; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Structure; Plant Stems; Pregnanes; Spleen; Structure-Activity Relationship; T-Lymphocytes
PubMed: 31550672
DOI: 10.1016/j.phytochem.2019.112127