RESUMO
Five new cholestane glycosides, named parisfargosides A-E (1-5), were isolated from the rhizomes of Paris fargesii. Their structures were elucidated on the basis of UV, HR-ESI-MS, 1D and 2D NMR data as well as chemical methods. The structures of all compounds contained α, ß-unsaturated ketone unit. Compounds 3-5 possessed a 16,23-cyclocholest skeleton with 6/6/6/5/5 condensed ring, and the absolute configurations of C-16 and C-23 were confirmed according to ROESY spectra with pyridined5 and DMSOd6 as solvents. In addition, the platelet aggregation activity and cytotoxic activity against five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480) of compounds 1-5 were evaluated.
Assuntos
Colestanos , Liliaceae , Colestanos/farmacologia , Glicosídeos/química , Humanos , Estrutura Molecular , Rizoma/químicaRESUMO
Rheumatoid arthritis (RA) is a debilitating autoimmune disease of unknown cause, characterized by infiltration and accumulation of activated immune cells in the synovial joints where cartilage and bone destructions occur. Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) was shown to be involved in the regulation of MDSC differentiation. The purpose of the present study was to investigate the effect of inhibition of SHIP1 on the expansion of MDSCs in RA using a collagen-induced inflammatory arthritis (CIA) mouse model. In DBA/1 mice, treatment with a small molecule-specific SHIP1 inhibitor 3α-aminocholestane (3AC) induced a marked expansion of MDSCs in vivo. Both pretreatment with 3AC of DBA/1 mice prior to CIA induction and intervention with 3AC during CIA progression significantly reduced disease incidence and severity. Adoptive transfer of MDSCs isolated from 3AC-treated mice, but not naïve MDSCs from normal mice, into CIA mice significantly reduced disease incidence and severity, indicating that the 3AC-induced MDSCs were the cellular mediators of the observed amelioration of the disease. In conclusion, inhibition of SHIP1 expands MDSCs in vivo and attenuates development of CIA in mice. Small molecule-specific inhibition of SHIP1 may therefore offer therapeutic benefit to patients with RA and other autoimmune diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Colestanos/farmacologia , Células Supressoras Mieloides/imunologia , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Artrite Experimental/genética , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Comunicação Celular , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Expressão Gênica , Humanos , Cápsula Articular/efeitos dos fármacos , Cápsula Articular/imunologia , Cápsula Articular/patologia , Camundongos , Camundongos Endogâmicos DBA , Camundongos Knockout , Células Supressoras Mieloides/citologia , Células Supressoras Mieloides/transplante , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/antagonistas & inibidores , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/imunologia , Índice de Gravidade de Doença , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/patologiaRESUMO
An extract of Galtonia regalis from the Natural Products Discovery Institute showed moderate antiplasmodial activity, with an IC50 value less than 1.25 µg/mL. The two known cholestane glycosides 1 and 2 and the five new cholestane glycosides galtonosides A-E (3-7) were isolated after bioassay-directed fractionation. The structures of the new compounds were determined by interpretation of their NMR and mass spectra. Among these compounds, galtonoside B (4) displayed the most potent antiplasmodial activity, with an IC50 value of 0.214 µM against the drug-resistant Dd2 strain of Plasmodium falciparum.
Assuntos
Antimaláricos/química , Colestanos/farmacologia , Glicosídeos/farmacologia , Asparagales/química , Colestanos/química , Colestanos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plasmodium falciparum/químicaRESUMO
Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-ß peptide (Aß42) are key pathogenic agents in Alzheimer's disease (AD). To investigate the relationship between Aß42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aß42-induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Colestanos/uso terapêutico , Fragmentos de Peptídeos/metabolismo , Espermina/análogos & derivados , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Caenorhabditis elegans , Linhagem Celular Tumoral , Colestanos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Fragmentos de Peptídeos/efeitos dos fármacos , Espermina/farmacologia , Espermina/uso terapêuticoRESUMO
Three new cholestane-type sterols bearing an unusual ∆22-24-oxo side chain, namely, dictyoptesterols A-C (1-3), were isolated from the brown alga Dictyopteris undulata Holmes, together with five known strutural analogues (4-8). Their structures were elucidated on the basis of by extensive spectroscopic analysis. The absolute configurations of the steroidal nuclei of the new compounds were proposed by a comparison of NMR data with those of related known compounds as well as biogenetic considerations. All of the isolates were evaluated in vitro for their potential to inhibit protein tyrosine phosphatase-1B (PTP1B) activity. The results showed that compounds 1-5 exhibited different levels of PTP1B inhibitory activities with IC50 values ranging from 3.03⯱â¯0.76 to 15.01⯱â¯2.88⯵M. In particular, compounds 3 and 4 showed promising inhibitory effects towards PTP1B with IC50 values of 3.03⯱â¯0.76 and 3.72⯱â¯0.40⯵M, respectively, when compared to the positive control oleanolic acid (IC50, 2.83⯱â¯0.39⯵M). The chemotaxonomic significance of these isolated ∆22-24-oxo cholestanes has also been discussed.
Assuntos
Colestanos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Phaeophyceae/química , Fitosteróis/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , China , Colestanos/farmacologia , Inibidores Enzimáticos/farmacologia , Estrutura Molecular , Fitosteróis/farmacologiaRESUMO
Phytochemical investigation of the tubers of Ophiopogon japonicus led to the isolation of five previously undescribed steroidal saponins, ophiojaponins A-E, together with twelve known ones. The structures of these isolated compounds were elucidated by detailed spectroscopic analyses and chemical methods. Ophiojaponins A-C are rare naturally occurring C29 steroidal glycosides possessing a homo-cholestane skeleton with an aromatized ring E. Ruscogenin 1-O-α-L-rhamnopyranosyl-(1 â 2)-4-O-sulfo-ß-D-fucopyranosido-3-O-ß-D-glucopyranoside was isolated as single component and its full spectroscopic data was reported for the first time. The isolated steroidal saponins were evaluated for their cytotoxicities against two human tumor cell lines MG-63 and SNU387. Among them, five known spirostane-type glycosides showed cytotoxic activity against both MG-63 and SNU387 cell lines with IC50 values ranging from 0.76 to 27.0 µM.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Colestanos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Ophiopogon/química , Tubérculos/química , Saponinas/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Colestanos/química , Colestanos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Saponinas/química , Saponinas/farmacologia , EstereoisomerismoRESUMO
Three new unusual 23-spirocholestane derivatives, ypsilanogenin (1), ypsilanogenin 3-O-ß-D-glucopyranoside (2), and 4'-acetylypsilanogenin 3-O-ß-D-glucopyranoside (3), were isolated from the whole plants of Ypsilandra thibetica. The structures of compounds 1-3 were deduced by spectroscopic and chemical methods, and the structure of 1 was further confirmed by a single-crystal diffraction analysis. All isolates were evaluated for their inhibitory activities against HIV-1.
Assuntos
Fármacos Anti-HIV/farmacologia , Glicosídeos/farmacologia , Liliaceae/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Colestanos/química , Colestanos/isolamento & purificação , Colestanos/farmacologia , Cristalografia por Raios X , Glicosídeos/química , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Plantas Medicinais , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Compostos de Espiro/química , Compostos de Espiro/isolamento & purificação , Compostos de Espiro/farmacologiaRESUMO
A phytochemical investigation of the seeds of Persian leek afforded the isolation of two new spirostane glycosides, persicosides A (1) and B (2), four new furostane glycosides, isolated as a couple of inseparable mixture, persicosides C1/C2 (3a/3b) and D1/D2 (4a/4b), one cholestane glycoside, persicoside E (5), together with the furostane glycosides ceposides A1/A2 and C1/C2 (6a/6b and 7a/7b), tropeosides A1/A2 and B1/B2 (8a/8b and 9a/9b), and ascalonicoside A1/A2 (10a/10b), already described in white onion, red Tropea onion, and shallot, respectively. Structure elucidation of the compounds was carried out by comprehensive spectroscopic analyses, including 2D NMR spectroscopy and MS spectrometry, and by chemical evidences. The chemical structure of new compounds were identified as (25S)-spirostan-2α,3ß,6ß-triol 3-O-[ß-d-glucopyranosyl-(1â3)] [ß-d-xylopyranosyl-(1â2)]-ß-d-glucopyranosyl-(1â4)-ß-d-galactopyranoside (1), (25S)-spirostan-2α,3ß,6ß-triol 3-O-[ß-d-xylopyranosyl-(1â3)] [α-l-rhamnopyranosyl-(1â2)]-ß-d-glucopyranosyl-(1â4)-O-ß-d-galactopyranoside (2), furosta-1ß,3ß,22ξ,26-tetraol 5-en 1-O-ß-d-glucopyranosyl (1â3)-ß-d-glucopyranosyl (1â2)-ß-d-galactopyranosyl 26-O-α-l-rhamnopyranosyl (1â2)-ß-d-galactopyranoside (3a,3b), furosta-2α,3ß,22ξ,26-tetraol 3-O-ß-d-glucopyranosyl (1â3)-ß-d-glucopyranosyl (1â2)-ß-d-galactopyranosyl 26-O-ß-d-glucopyranoside (4a,4b), (22S)-cholesta-1ß,3ß,16ß,22ß-tetraol 5-en 1-O-α-l-rhamnopyranosyl 16-O-α-l-rhamnopyranosyl (1â2)-ß-d-galactopyranoside (5). Antifungal activity of the isolated compounds was evaluated against the fungal pathogens, Penicillium italicum, Aspergillus niger, Trichoderma harzianum and Botrytis cinerea. Persicosides A and B showed the higher activity on the tested fungi highlighting the positive effect of the spirostane skeleton on the antifungal activity.
Assuntos
Allium/química , Antifúngicos/farmacologia , Colestanos/farmacologia , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Antifúngicos/química , Colestanos/química , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Saponinas/químicaRESUMO
Phytochemical investigation of the ethanol extract obtained from the aerial parts of the Euphorbia altotibetic PAULS. Grown in China resulted in the isolation of three new cholestane-type and three new ergostane-type steroids (cholest-5-en-2ß, 4ß-diol; cholest-5-en-1ß, 4ß-diol; cholest-5-en-1α, 3ß, 4α -triol; (22E)-ergosta-7,9,22-trien- 3ß-ol ß-D-glucoside; 5α-methoxy-(22E)-ergosta-7,9,22-trien-3ß-ol ß-D-glucoside; 6ß- methoxy-(22E)-ergosta-7,9,22-trien-3ß-ol ß-D-glucoside), along with seven known compounds. Their structures were established by extensive one- and two-dimensional NMR spectroscopy, as well as other spectrum and chemical analysis. The isolated new steroids exhibited potent anti-tumor activity against the HeLa cell and Hep-G2 cell with the 50% inhibiting concentration values ranging from 1.9 to 9.2 µg/mL.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Colestanos/farmacologia , Ergosterol/análogos & derivados , Ergosterol/farmacologia , Euphorbia/química , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Colestanos/química , Colestanos/isolamento & purificação , Ergosterol/química , Ergosterol/isolamento & purificação , Células HeLa , Células Hep G2 , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
Six new cholestane glycosides (1, 5, 6, 10, 12, and 13) and two new sterols (9 and 11), along with five known compounds (2-4, 7, and 8), were isolated from the underground parts of Chamaelirium luteum (Liliaceae). The structures of these new compounds were determined by spectroscopic analysis and the results of hydrolytic cleavage. The isolated compounds and aglycones were evaluated for their cytotoxic activity against HL-60 human leukemia cells. Compounds 6a, 10a, 12a, 13, and 13a were cytotoxic to HL-60 cells, with IC50 values of 12.8, 9.8, 15.3, 6.2, and 10.2 µM, respectively.
Assuntos
Antineoplásicos/farmacologia , Colestanos/farmacologia , Glicosídeos/farmacologia , Liliaceae/química , Fitosteróis/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Colestanos/química , Colestanos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Células HL-60 , Humanos , Hidrólise , Concentração Inibidora 50 , Leucemia Promielocítica Aguda , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fitosteróis/química , Fitosteróis/isolamento & purificação , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Plantas MedicinaisRESUMO
The chloroform/methanol extract of the red alga, Laurencia papillosa, collected from the Red Sea in Saudi Arabia, was found to contain two cholestane derivatives: 3alpha, 6alpha-dihydroxy-5beta-cholestan-12-one (1) and the known, 6beta-hydroxycholest-4-en-3-one (2), which was isolated separately in a pure form for the first time. In addition to these compounds, a new aldehyde derivative, (E)-2-{(E) tridec-2-en-2-yl} heptadec-2-enal (3), was isolated. The structures of all compounds were established based on extensive spectroscopic (1D and 2D NMR, UV, IR) and mass spectrometric studies. All compounds, except 2, were tested for their antifungal activity. Significant activities were associated with 1 and 3 against Candida albicans, Aspergillus fumigatus, and A. flavus.
Assuntos
Aldeídos/isolamento & purificação , Antifúngicos/isolamento & purificação , Colestanos/isolamento & purificação , Rodófitas/química , Aldeídos/química , Aldeídos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Colestanos/química , Colestanos/farmacologia , Espectroscopia de Ressonância MagnéticaRESUMO
Trodusquemine (MSI-1436) causes rapid and reversible weight loss in genetic models of obesity. To better predict the potential effects of trodusquemine in the clinic, we investigated the effects of trodusquemine treatment in a murine model of diet-induced obesity (DIO). Trodusquemine suppressed appetite, reduced body weight (BW) in a fat-specific manner, and improved plasma insulin and leptin levels in mice. Screening assays revealed that trodusquemine selectively inhibited protein-tyrosine phosphatase 1B (PTP1B), a key enzyme regulating insulin and leptin signaling. Trodusquemine significantly enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) beta and STAT3, direct targets of PTP1B, in HepG2 cells in vitro and/or hypothalamic tissue in vivo. These data establish trodusquemine as an effective central and peripheral PTP1B inhibitor with the potential to elicit noncachectic fat-specific weight loss and improve insulin and leptin levels.
Assuntos
Apetite/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Colestanos/farmacologia , Hipolipemiantes/farmacologia , Obesidade/tratamento farmacológico , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Espermina/análogos & derivados , Redução de Peso/efeitos dos fármacos , Animais , Dieta , Modelos Animais de Doenças , Células Hep G2 , Humanos , Hipotálamo/efeitos dos fármacos , Insulina/sangue , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos AKR , Camundongos Obesos , Obesidade/metabolismo , Fosforilação , Receptor de Insulina/metabolismo , Fator de Transcrição STAT3/metabolismo , Espermina/farmacologiaRESUMO
In a previous work our group showed that some synthetic stigmastanes may play a role in immune-mediated inflammation. In this paper we report the syntheses of a series of new steroidal compounds derived from dehydroepiandrosterone and stigmasterol, and the evaluation of their in vitro inhibitory activity of the TNF-alpha production by macrophages. A preliminary qualitative structure-activity relationship was established.
Assuntos
Androstanos/síntese química , Androstanos/farmacologia , Colestanos/síntese química , Colestanos/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Androstanos/química , Animais , Linhagem Celular , Colestanos/química , Desidroepiandrosterona/química , Avaliação Pré-Clínica de Medicamentos , Fatores Imunológicos/síntese química , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Camundongos , Estrutura Molecular , Estigmasterol/química , Relação Estrutura-AtividadeRESUMO
This study was performed to investigate the reactivity of 5alpha-cholestan-3-one (1) towards various chemical reagents to produce new steroidal heterocyclic derivatives. The aminothieno[2, 3:2, 3]cholestane derivative 2 was synthesized according to Gewald's conditions. The diazonium salt of compound 2 coupled with malononitrile to afford dicyanomethylenhydrazinothieno[2', 3':2, 3]cholestane derivative 5. The behavior of compound 5 towards nitrogen nucleophiles and several active methylene reagents was investigated. Additionally, a variety of steroidal heterocyclic derivatives like compounds 15a, b-22a, b were synthesized starting with 5alpha-cholestan-3-one (1). The structures of the compounds were established based on the analytical and spectral data. The in vitro antimicrobial activity of some newly synthesized compounds against bacteria and fungi was studied.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Colestanos/síntese química , Colestanos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Ampicilina/farmacologia , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/farmacologia , Técnicas In Vitro , Testes de Sensibilidade Microbiana/métodos , Nistatina/farmacologiaRESUMO
A phytochemical investigation of the stems of the South Brazilian endemic species Raulinoa echinata has led to the isolation of two new methoxylated protolimonoid epimers (1 and 2) together with the known melianone and melianodiol. The leaves afforded three glabretal-type triterpene derivatives esterified by N-methylanthranilic acid (3-5). Compounds 1 and 2 displayed weak inhibitory activity when assayed in vitro against trypomastigote forms of Trypanosoma cruzi. Compounds 1-5 were inactive in a brine shrimp (Artemia salina) lethality test.
Assuntos
Antiprotozoários/isolamento & purificação , Colestanos/isolamento & purificação , Plantas Medicinais/química , Rutaceae/química , Triterpenos/isolamento & purificação , ortoaminobenzoatos/isolamento & purificação , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Artemia/efeitos dos fármacos , Brasil , Colestanos/química , Colestanos/farmacologia , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , ortoaminobenzoatos/química , ortoaminobenzoatos/farmacologiaRESUMO
Two new cholestane bisdesmosides (1, 2) based upon (22S)-cholest-5-ene-3 beta,16 beta,22-triol with an acetyl group at the sugar moiety and three new ones (3-5) based upon (22S)-cholest-5-ene-1 beta,3 beta,16 beta,22-tetrol, along with a known cholestane glycoside, were isolated from the bulbs of Galtonia candicans. The structures of the new compounds were determined by spectroscopic analysis and chemical transformations.
Assuntos
Colestanos/isolamento & purificação , Glicosídeos/isolamento & purificação , Liliaceae/química , Plantas Medicinais/química , Colestanos/química , Colestanos/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Glicosídeos/química , Glicosídeos/farmacologia , Células HL-60/efeitos dos fármacos , Humanos , Japão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Further phytochemical analysis of the bulbs of Ornithogalum saundersiae has yielded two new cytotoxic cholestane triglycosides (1 and 2). The structures of these compounds were determined by spectroscopic analysis, including 2D NMR spectroscopic data, and the results of hydrolytic cleavage. Compounds 1 and 2 and several analogues were evaluated for their cytotoxicity against HL-60 cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Colestanos/isolamento & purificação , Glicosídeos/isolamento & purificação , Liliaceae/química , Raízes de Plantas/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/farmacologia , Colestanos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/farmacologia , Células HL-60 , Humanos , Hidrólise , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Células Tumorais CultivadasRESUMO
A new lanostanoid ester glucoside, 3 alpha-acetoxy-5 alpha-lanosta-8,24-dien-21-oic acid ester beta-d-glucoside (1), and a known steroid, 2 beta,3 alpha,9 alpha-trihydroxy-5 alpha-ergosta-7,22-diene (2), were isolated from the fruit bodies of Ganoderma tsugae and their structures determined by spectroscopic methods. To study the cytotoxicity of 1 and 2, the changes of DNA content in human hepatocytes (Hep 3B) were studied. A sub-G1 cell stage was drastically increased after 24-h incubation with 1 (24 micrograms/mL). Compound 2 (100 micrograms/mL) inhibited the cell cycle progression of Hep 3B cells at the G2/M phase with an IC50 value of about 87.1 micrograms/mL. These results indicate that 1 causes cell death by apoptosis and 2 may possess the activity of cell cycle inhibition.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Colestanos/isolamento & purificação , Glucosídeos/isolamento & purificação , Plantas Medicinais/química , Esteroides/toxicidade , Colestanos/farmacologia , DNA/química , DNA/efeitos dos fármacos , Citometria de Fluxo , Glucosídeos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Células Tumorais CultivadasAssuntos
Colestanos/isolamento & purificação , Plantas Medicinais/química , Antifúngicos/farmacologia , Colestanos/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Fusarium/efeitos dos fármacos , Índia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectrofotometria InfravermelhoRESUMO
A novel 16,23-epoxy-5 beta-cholestane triglycoside (1) was isolated from the bulbs of Ornithogalum saundersiae (Liliaceae). The structure was determined by extensive spectroscopic analysis. The conformation of the E-ring part of 1 was studied through molecular mechanics and molecular dynamics calculation methods. Compound 1 potently inhibited proliferation of peripheral blood lymphocytes provided from a chronic renal failure patient without causing any cytotoxicity in the lymphocytes and HL-60 human leukemia cells.