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1.
Nat Prod Res ; 34(2): 311-316, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30404547

RESUMO

Development of a novel agent for control of schistosomiasis is a mandate. In-vitro anti-schistosomal activity of the aerial parts of Huernia saudi-arabica were examined. Chromatographic investigations of the ethanol extract (EE) were afforded three compounds. Pregnane glycoside (CI) 12-ß-p-hydroxy-benzoyl-20-O-acetyl-boucerin-3-O-ß-D-glucopyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside, in addition to two flavonoids (CII) luteolin-4'-O-ß-D-neohesperidoside and (CIII)quercetin-3-rutinoside were recognized via spectral analysis. The schistosomicidal effects were evaluated using scanning electron microscope (SEM). In-vitro bioassays on the viability (mobility, morphological changes and mortality) of Schistosoma mansoni adults, cercariae, miracidia and eggs at different concentrations 2.5, 5, 12.5, 25 and 50 µg/ml of EE and 2.6, 5.2, 13, 26 and 52 µM of CI in incubation times 1,2,4,6,12hrs were carried out. EE and CI evidenced in-vitro anti-schistosomal activity with a dose and incubation time-dependent fashion. The effect of EE and CI was evident by the topography damage showed by SEM. EE proved moderate in-vitro cytotoxicity with IC50 of 8.48 µg/ml.


Assuntos
Apocynaceae/química , Glicosídeos/farmacologia , Pregnanos/farmacologia , Esquistossomicidas/isolamento & purificação , Animais , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glicosídeos/isolamento & purificação , Extratos Vegetais/química , Pregnanos/isolamento & purificação , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia
2.
Phytochemistry ; 168: 112127, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31550672

RESUMO

Five undescribed C21 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 C21 pregnane glycosides showed immunosuppressive activity in a concentration-dependent manner. Moreover, epigycoside E exhibited a potent immunosuppressive effect, and the IC50 value on Con A-stimulated mice splenocytes was 22.1 ±â€¯6.4 µM. Epigycoside E also caused G0/G1 arrest, and inhibited TNF-α and IL-2 production.


Assuntos
Apocynaceae/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Pregnanos/isolamento & purificação , Pregnanos/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Concanavalina A/antagonistas & inibidores , Concanavalina A/farmacologia , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Glicosídeos/química , Imunossupressores/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Estrutura Molecular , Caules de Planta/química , Pregnanos/química , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos
3.
J Enzyme Inhib Med Chem ; 34(1): 684-691, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30777494

RESUMO

Synthetic progesterone and 5α/ß-pregnane-3,20-dione derivatives were evaluated as in vitro and in vivo modulators of multidrug-resistance (MDR) using two P-gp-expressing human cell lines, the non-steroidogenic K562/R7 erythroleukaemia cells and the steroidogenic NCI-H295R adrenocortical carcinoma cells, both resistant to doxorubicin. The maximal effect in both cell lines was observed for 7α-O-benzoyloxy,11α(R)-O-tetrahydropyranyloxy-5ß-pregnane-3,20-dione 4. This modulator co-injected with doxorubicin significantly decreased the tumour size and increased the survival time of immunodeficient mice xenografted with NCI-H295R or K562/R7 cells.


Assuntos
Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Pregnanos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos SCID , Conformação Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Pregnanos/síntese química , Pregnanos/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
4.
Nat Prod Res ; 33(22): 3210-3214, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29726713

RESUMO

Phytochemical investigation on the ethyl acetate fraction of the leaves of Epigynum cochinchinensis led to the isolation of a new C21 pregnane glycoside, epigycoside B (1), together with three known analogues. Their structures were elucidated on the basis of extensive spectroscopic techniques, including UV, MS, and NMR experiments, as well as the chemical methods. Compound 1 displayed in vitro immunosuppressive activity against concanavalin A (Con A)/Lipopolysaccharides (LPS)-stimulated proliferation of mice splenocyte. The activity was significant as compared with control group at 50 µM concentration.


Assuntos
Apocynaceae/química , Glicosídeos/farmacologia , Imunossupressores/isolamento & purificação , Pregnanos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Concanavalina A/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/imunologia , Glicosídeos/isolamento & purificação , Imunossupressores/química , Imunossupressores/farmacologia , Lipopolissacarídeos , Camundongos , Estrutura Molecular , Folhas de Planta/química , Pregnanos/química , Pregnanos/imunologia , Pregnanos/isolamento & purificação , Análise Espectral , Baço/citologia
5.
Nat Prod Res ; 33(11): 1570-1576, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29334245

RESUMO

A new polyhydroxylated pregnane, named lß,2ß,3ß,4ß,5ß,6ß-hexolhydroxy-pregn-16-en-20-one (1), along with nine known (2-10) steroidal saponins were isolated from the whole plant of Reineckia carnea. Structure elucidations of all compounds were established by interpretation of their NMR spectral data, HR-ESI-MS and comparing with literatures. In addition, these compounds were evaluated with anticomplement activity. The result showed that compound 1 exhibited anticomplement effects with the CH50 values of 0.043 mg/mL, but saponins (2-10) showed no inhibition. Interestingly, hydrolysis of steroidal saponins (2-10) resulted in its aglycones (2a-10a) correspondingly which showed anticomplement activity with the CH50 values of 0.049-0.156 mg/mL.


Assuntos
Asparagaceae/química , Inativadores do Complemento/farmacologia , Esteroides/química , Esteroides/farmacologia , Animais , Inativadores do Complemento/química , Avaliação Pré-Clínica de Medicamentos/métodos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Cobaias , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pregnanos/química , Pregnanos/farmacologia , Saponinas/química , Saponinas/farmacologia , Ovinos , Espectrometria de Massas por Ionização por Electrospray
6.
Asian Pac J Cancer Prev ; 19(6): 1457-1464, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29936715

RESUMO

Objective: This study aims to isolate the active anticancer compound from ethyl acetate fraction extracted from the roots of Calotropis gigantea and to determine the operating mechanism of the isolates towards WiDr colon cancer cells. Methods: the isolation was conducted by using bioassay guided isolation approach method. The cytotoxic potential was determined by using MTT method. The chemical structure was identified by using UPLCMS/MS and NMR-1H spectroscopy. The cell cycle arrest and apoptosis induction were determined by flow cytometry method. The expression of caspase-8 was determined by immunocytochemistry method. Results: The results showed that the active compounds are obtained calotroposid A compound which is glycosides terpenoids. Calotroposide A is capable of inhibiting the growth of WiDr colon cancer cells at IC50 17.23µg/ml. Cell apoptosis induction took place and was indicated by cell apoptosis increase, S and G2/M accumulation and by caspase-8 expression. Conclusion: Calotroposide A induces anticancer activity against WiDr colon cancer cells by means of apoptosis induction mechanism through extrinsic pathway with increased expression of caspase-8.


Assuntos
Apoptose/efeitos dos fármacos , Calotropis/química , Caspase 8/metabolismo , Neoplasias do Colo/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pregnanos/farmacologia , Saponinas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células Tumorais Cultivadas
7.
Clin Orthop Relat Res ; 476(6): 1311-1323, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29698291

RESUMO

BACKGROUND: Infection of open fractures remains a significant cause of morbidity and mortality to patients worldwide. Early administration of prophylactic antibiotics is known to improve outcomes; however, increasing concern regarding antimicrobial resistance makes finding new compounds for use in such cases a pressing area for further research. CSA-90, a synthetic peptidomimetic compound, has previously demonstrated promising antimicrobial action against Staphylococcus aureus in rat open fractures. However, its efficacy against antibiotic-resistant microorganisms, its potential as a therapeutic agent in addition to its prophylactic effects, and its proosteogenic properties all require further investigation. QUESTIONS/PURPOSES: (1) Does prophylactic treatment with CSA-90 reduce infection rates in a rat open fracture model inoculated with S aureus, methicillin-resistant S aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE) as measured by survival, radiographic union, and deep tissue swab cultures? (2) Does CSA-90 reduce infection rates when administered later in the management of an open fracture as measured by survival, radiographic union, and deep tissue swab cultures? (3) Does CSA-90 demonstrate a synergistic proosteogenic effect with bone morphogenetic protein 2 (BMP-2) in a noninfected rat ectopic bone formation assay as assessed by micro-CT bone volume measurement? (4) Can CSA-90 elute and retain its antimicrobial efficacy in vitro when delivered using clinically relevant agents measured using a Kirby-Bauer disc diffusion assay? METHODS: All in vivo studies were approved by the local animal ethics committee. In the open fracture studies, 12-week-old male Wistar rats underwent open midshaft femoral fractures stabilized with a 1.1-mm Kirschner wire and 10 µg BMP-2 ± 500 µg CSA-90 was applied to the fracture site using a collagen sponge along with 1 x 10 colony-forming units of bacteria (S aureus/MRSA/MRSE; n = 10 per group). In the delayed treatment study, débridement and treatment with 500 µg CSA-90 were performed at Day 1 and Day 5 after injury and bacterial insult (S aureus). All animals were reviewed daily for signs of local infection and/or sepsis. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats showing osteolysis and/or declining overall health were culled at his instruction. The primary outcome of both fracture studies was fracture infection, incorporating survival, radiographic union, and deep tissue swab cultures. For the ectopic bone formation assay, 0 to 10 µg BMP-2 and 0 to 500 µg CSA-90 were delivered on a collagen sponge into bilateral quadriceps muscle pouches of 8-week-old rats (n = 10 per group). Micro-CT quantification of bone volume and descriptive histologic analysis were performed for all in vivo studies. Modified Kirby-Bauer disc diffusion assays were used to quantify antimicrobial activity in vitro using four different delivery methods, including bone cement. RESULTS: Infection was observed in none of the MRSA inoculated open fractures treated with CSA-90 with 10 of 10 deep tissue swab cultures negative at the time of cull. Median survival was 43 days (range, 11-43 days) in the treated group versus 11 days (range, 8-11 days) in the untreated MRSA inoculated group (p < 0.001). However, delayed débridement and treatment of open fractures with CSA-90 at either Day 1 or Day 5 did not prevent infection, resulting in early culls by Day 21 with positive swab cultures (10 of 10 for each time point). Maximal ectopic bone formation was achieved with 500 µg CSA-90 and 10 µg BMP-2 (mean volume, 9.58 mm; SD, 7.83), creating larger bone nodules than formed with 250 µg CSA-90 and 10 µg BMP-2 (mean volume, 1.7 mm; SD, 1.07; p < 0.001). Disc diffusion assays showed that CSA-90 could successfully elute from four potential delivery agents including calcium sulphate (mean zone of inhibition, 11.35 mm; SD, 0.957) and bone cement (mean, 4.67 mm; SD, 0.516). CONCLUSIONS: CSA-90 shows antimicrobial action against antibiotic-resistant Staphylococcal strains in vitro and in an in vivo model of open fracture infection. CLINICAL RELEVANCE: The antimicrobial properties of CSA-90 combined with further evidence of its proosteogenic potential make it a promising compound to develop further for orthopaedic applications.


Assuntos
Antibioticoprofilaxia/métodos , Fraturas do Fêmur/tratamento farmacológico , Fraturas Expostas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Pregnanos/farmacologia , Propilaminas/farmacologia , Infecções Estafilocócicas/prevenção & controle , Animais , Modelos Animais de Doenças , Fraturas do Fêmur/microbiologia , Fraturas Expostas/microbiologia , Masculino , Ratos , Ratos Wistar , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/efeitos dos fármacos
8.
Bioorg Med Chem Lett ; 28(7): 1252-1256, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29526485

RESUMO

Bioassay-guided fractionation of the methanolic extract from the roots of Cynanchum atratum has resulted in the isolation of three new pregnane glycosides (1-3) along with four known compounds (4-7). Their structures were identified by analysis of the spectroscopic data including extensive 2D NMR. All of the isolates were evaluated for their potential to inhibit the melanin production in α-melanocyte stimulating hormone (α-MSH)-activated B16 melanoma cells. Of these, compounds 4-7 dose-dependently inhibited the melanin production with the IC50 values ranging from 4 µM to 33 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cynanchum/química , Glicosídeos/farmacologia , Melaninas/antagonistas & inibidores , Melanoma Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Pregnanos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Pregnanos/química , Pregnanos/isolamento & purificação , Relação Estrutura-Atividade
9.
Phytochemistry ; 147: 147-157, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29331903

RESUMO

Dregea sinensis Hemsl is an important herbal medicine in the Dai nationality of China. Its prominent clinical application has generated interest in the polyoxypregnane glycosides of the plant. This paper describes an extension of previous research on the polyoxypregnane di- and triglycosides of D. sinensis, aiming at identifying related tetraglycosides. On the basis of HPLC-ESI-MSn analysis in positive mode, twenty-five previously undescribed polyoxypregnane tetraglycosides were characterized (regarding molecular masses and fragmentation in MSn) from an ethyl acetate fraction that was not previously investigated. Guided by MSn fragmentation and known structures of related di- and triglycosides from D. sinensis, tentative structures were predicted from the MS data. In order to test the predictions, eight of the glycosides were isolated and their structures were elucidated by 1D and 2D NMR methods, confirming the tentative predictions. Finally, the cytotoxicity of the isolates was evaluated on several human cell lines with little effect in general, even though slight inhibitory effects of four polyoxypregnane glycosides were detected at 10 µM against the human leukemia cell line HL-60.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apocynaceae/química , Medicamentos de Ervas Chinesas/química , Plantas Medicinais/química , Pregnanos/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , China , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Medicina Tradicional Chinesa , Estrutura Molecular , Pregnanos/isolamento & purificação , Pregnanos/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
10.
Bioorg Med Chem Lett ; 28(3): 330-333, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29292227

RESUMO

Phytochemical investigation of the root barks of Periploca chrysantha D. S. Yao, X. C. Chen et J. W. Ren (Asclepiadaceae) led to the elucidation of four new spiroorthoester group-containing pregnane glycosides (1-4), named periplosides W-Y and 3-O-formyl-periploside F. Their structures were elucidated on the basis of extensive spectroscopic analysis. The four new pregnane glycosides (1-4) were found to exhibit significantly inhibitory activities against the proliferation of B and T lymphocytes and favorable selective index comparable to those of cyclosporin A.


Assuntos
Linfócitos B/efeitos dos fármacos , Glicosídeos/farmacologia , Periploca/química , Casca de Planta/química , Raízes de Plantas/química , Pregnanos/farmacologia , Compostos de Espiro/farmacologia , Linfócitos T/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glicosídeos/química , Humanos , Conformação Molecular , Pregnanos/química , Compostos de Espiro/síntese química , Compostos de Espiro/química , Relação Estrutura-Atividade
11.
Nat Prod Res ; 32(3): 261-267, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28714348

RESUMO

Two new steroidal glycosides 1 and 2, along with three known ones (3-5), were isolated from the 95% ethanol extract of the roots of Cynanchum limprichtii Schltr. The structure of the new compounds was elucidated as 3-O-α-L-diginopyranosyl-(1→4)-ß-D-digitoxopyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-thevetopyranosyl-14, 16:15, 20:18, 20-triepoxy-14, 15-secopregn-4, 6, 8 (14)-triene (1) and 3-O-α-L-cymaropyranosyl-(1→4)-ß-D-digitoxopyranosyl- (1→4)-ß-D-3-demethyl-2-deoxythevetopyranosyl-14, 16: 15, 20: 8, 20-triepoxy-14, 15-secopregn-5, 8 (14)-diene (2) on the basis of spectroscopic analysis together with acidic hydrolysis. All compounds showed cytotoxic activity against the human cancer cell line HL60, with IC50 values of 55.36, 65.41, 17.88, 17.68 and 33.5 µM, respectively. While, only compound 3 showed cytotoxicity against the Caco-2 cell line, with an IC50 value of 67.47 µM.


Assuntos
Cynanchum/química , Glicosídeos/química , Raízes de Plantas/química , Pregnanos/química , Células CACO-2 , Glicosídeos/farmacologia , Células HL-60 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Pregnanos/farmacologia
12.
Nat Prod Res ; 32(11): 1260-1266, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28641456

RESUMO

A new pregnane, 3α-hydroxy-7-ene-6,20-dione (1), and five known steroids (2-6), along with one known steroidal glycoside (7) were obtained from the fungus Cladosporium sp. WZ-2008-0042 cultured from a gorgonian Dichotella gemmacea collected from the South China Sea. The structure and absolute configuration of the new compound (1) were elucidated by comprehensive spectroscopic data and X-ray diffraction data. The compound has a rare configuration of 3α-OH that is different from most of pregnanes. All of the isolated compounds were evaluated for their antiviral activities against respiratory syncytial virus (RSV). Among them, 1 exhibited potential antiviral activity with the IC50 value of 0.12 mM.


Assuntos
Antivirais/farmacologia , Cladosporium/química , Pregnanos/química , Animais , Antozoários/microbiologia , Antibacterianos/química , Antibacterianos/farmacologia , Antivirais/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pregnanos/farmacologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray , Esteroides/química , Difração de Raios X
13.
BMC Microbiol ; 17(1): 167, 2017 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-28747178

RESUMO

BACKGROUND: Cationic antibacterial peptides (CAPs) and synthetic molecules mimicking the amphiphilic structure of CAPs, such as ceragenins, are promising compounds for the development of new antimicrobials. RESULTS: We tested the in vitro activity of ceragenins CSA-13 and CSA-131 against several anaerobic bacteria including Bacteroides spp. and Clostridium difficile. We compared results to the activity of cathelicidin LL-37, metronidazole and nanosystems developed by attachment of CSA-13 and CSA-131 to magnetic nanoparticles (MNPs). The antibacterial effect was tested using killing assay and modified CLSI broth microdilution assay. Ceragenins CSA-13 and CSA-131 displayed stronger bactericidal activity than LL-37 or metronidazole against all of the tested bacterial strains. Additionally CSA-131 revealed an enhanced ability to prevent the formation of Bacteroides fragilis and Propionibacterium acnes biofilms. CONCLUSIONS: These data confirmed that ceragenins display antimicrobial activity against a broad range of microorganisms including anaerobic bacteria and deserve further investigations as compounds serving to develop new treatment against anaerobic and mixed infections.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Bactérias Anaeróbias/crescimento & desenvolvimento , Nanopartículas de Magnetita/química , Pregnanos/farmacologia , Esteroides/farmacologia , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Pregnanos/química , Esteroides/química
14.
J Nat Prod ; 80(6): 1714-1724, 2017 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-28561586

RESUMO

Five 12,20-epoxypregnane glycosides (1-3, 5, and 6) and two 11,12-seco-pregnane glycosides (4 and 7) with spirodilactone motifs, as well as spirodilactone cleavage products 8 and 9, were isolated from the stems of Hoya kerrii. The relative configurations of the three related skeletons were supported by ROESY experiments and X-ray crystallographic analyses. The isolates were evaluated for their anti-inflammatory activity based on the inhibition of NO production in RAW264.7 cells, and some showed IC50 values ranging from 12.6 to 96.5 µM. The most potent compound, 9a, was also examined for its anti-inflammatory mechanism against mRNA expression and was found to down-regulate mRNA expression of iNOS and COX-2 in a dose-dependent manner.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Apocynaceae/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Pregnanos/isolamento & purificação , Pregnanos/farmacologia , Animais , Anti-Inflamatórios/química , Cristalografia por Raios X , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Glicosídeos/química , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Conformação Molecular , Estrutura Molecular , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Caules de Planta/química , Pregnanos/química , Tailândia
15.
Steroids ; 125: 27-32, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28636871

RESUMO

Five new pregnane-type steroidal glycosides, named menarandrosides A-E (1-2, 5-7) were isolated from the aerial parts of Cynanchum menarandrense, together with three known compounds, carumbelloside I (3), carumbelloside II (4), and pregnenolone-3-O-gentiobioside (8). Their structures were determined on the basis of spectroscopic analyses including NMR and mass spectrometry, reporting C-21 steroids glycosylated only by one or two glucose moieties. Compounds were then investigated for their potential to stimulate glucagon-like peptide-1 (GLP-1) secretion in intestinal cells; although none of the pure compounds had any influence, the fraction enriched in pregnanes exhibited a significant activity, suggesting a possible synergistic effect. Furthermore, none of the purified compounds affected cell viability.


Assuntos
Cynanchum/química , Glicosídeos/química , Glicosídeos/farmacologia , Pregnanos/química , Pregnanos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glicosídeos/isolamento & purificação , Intestinos/citologia , Pregnanos/isolamento & purificação
16.
Bioorg Med Chem Lett ; 27(12): 2736-2741, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28456553

RESUMO

An unprecedented spinaceamine-bearing pregnane namely scleronine (1) was isolated from a Chinese soft coral Scleronephthya sp. Its structure was determined on the basis of 1D and 2D NMR spectroscopic analyses in association with the HRESIMS data, while the absolute configurations were deduced by the single-crystal X-ray diffraction analysis. In addition, a dehydrogenated analogue (3) was synthesized through six steps with pregna-1,20-dien-3-one (2) as a precursor. The significantly inhibitory effects of 1 and 3 against the migration of tumor cells A549 and B16 accompanying the down-regulation of key genes (TGFß, TNFα, IL-1ß, and IL-6) were observed. These findings suggested that both 1 and 3 are potential for therapeutic usage aiming at cancer metastasis inhibition.


Assuntos
Antozoários/química , Compostos Heterocíclicos com 2 Anéis/farmacologia , Pregnanos/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Compostos Heterocíclicos com 2 Anéis/química , Compostos Heterocíclicos com 2 Anéis/isolamento & purificação , Humanos , Estrutura Molecular , Pregnanos/química , Pregnanos/isolamento & purificação , Teoria Quântica , Relação Estrutura-Atividade
17.
Phytochemistry ; 140: 1-15, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28437621

RESUMO

Twenty-three undescribed previously C21 steroidal glycosides, named saccatols D-K and cynsaccatols I-W, together with six known analogs were isolated from the roots of Cynanchum auriculatum Royle ex Wight (Apocynaceae). Their structures were elucidated by a variety of spectroscopic techniques, as well as HRESIMS and GC method. All isolated compounds were tested their neuroprotective effects on the model of H2O2-induced damage to PC12 cells. Except saccatols D-F, J, cynsaccatol V and wilfoside A, other twenty-three isolates produced significantly activities against H2O2-induced cell damage (P < 0.001). Furthermore, cynsaccatols I, N, O and S can obvious inhibition of damaged PC12 cell apoptosis at their dosages of 1 µM by Annexin V-FITC/PI double staining assay with flow cytometry.


Assuntos
Cynanchum/química , Glicosídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Pregnanos/farmacologia , Animais , Apoptose , Glicosídeos/química , Peróxido de Hidrogênio/toxicidade , Estrutura Molecular , Células PC12 , Raízes de Plantas/química , Pregnanos/química , Ratos
18.
J Ethnopharmacol ; 203: 110-119, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28363522

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs. Polyoxypregnanes (POPs) are identified as main constituents of this herb, and three of them have been reported to exhibit P-gp modulatory effect and thus reverse MDR. Therefore, it is of great necessity to investigate more POPs that have potential to reverse transporters-mediated MDR. AIM OF THE STUDY: We aimed to identify POPs as the chemical basis responsible for circumventing ABC transporters-mediated MDR by M. tenacissima. MATERIALS AND METHODS: The MDR reversal effects of M. tenacissima crude extract together with a series of isolated POPs were evaluated on several MDR cancer cell lines that overexpress P-gp, MRP1 or ABCG2. The activities of P-gp, MRP1 and ABCG2 were determined by the flow cytometry-based substrate efflux assay. Molecular docking of POPs to a three-dimensional human P-gp homology structure was also performed. RESULTS: The crude extract of M. tenacissima was firstly found to circumvent P-gp-mediated MDR. Then, 11 polyoxypregnane compounds (POPs) isolated from this herb were found to overcome P-gp-, MRP1- and/or ABCG2-mediated MDR. Further mechanistic study delineated that the reversal of MDR by these POPs was due to significant increase in the intracellular concentrations of the substrate anticancer drugs via their inhibition of different ABC transporter-mediated efflux activities. Furthermore, molecular docking revealed that POPs with P-gp modulatory effect bound to P-gp and fitted well into the cavity between the alpha and beta subunit of P-gp via forming hydrogen bonds. In addition, several key structural determinants for inhibition of P-gp, MRP1 or ABCG2 by POPs were illustrated. CONCLUSIONS: Our findings advocated the rational use of M. tenacissima to enhance efficacies of conventional anticancer drugs in tumors with ABC drug transporters-mediated MDR. Furthermore, 11 POPs were found to contribute to MDR reversal effect of M. tenacissima via inhibition of different ABC efflux transporters.


Assuntos
Antineoplásicos/farmacologia , Marsdenia/química , Extratos Vegetais/farmacologia , Pregnanos/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Humanos , Simulação de Acoplamento Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Pregnanos/isolamento & purificação
19.
Nat Prod Res ; 31(24): 2893-2899, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28361559

RESUMO

Chemical investigation on the aqueous fraction of the stems of Epigynum cochinchinensis led to the isolation of a new pregnane glycoside named as epigycoside A (1) along with three known analogues (2-4). The structure of compound 1 was elucidated by means of spectroscopic techniques, including HRESIMS, and 1D and 2D NMR experiments. The immunosuppressive activity of 1 was evaluated by an in vitro model of concanavalin A-induced mice splenocytes proliferation. Compound 1 showed significant inhibitory activity in a dose-dependent manner, closer to the efficacy of positive control, dexamethasone, at a concentration of 50 µM.


Assuntos
Apocynaceae/química , Glicosídeos/isolamento & purificação , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Pregnanos/isolamento & purificação , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Glicosídeos/química , Glicosídeos/farmacologia , Imunossupressores/química , Camundongos , Estrutura Molecular , Caules de Planta/química , Pregnanos/química , Pregnanos/farmacologia , Baço/citologia
20.
J Nat Prod ; 80(4): 1102-1109, 2017 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-28294615

RESUMO

Further phytochemical investigation of the root bark of Periploca sepium afforded nine new spiro-orthoester group-containing pregnane-type glycosides termed periplosides O-V and 3-O-formyl-periploside A. The structures of these glycosides along with the absolute configuration of the unique seven-membered formyl acetal-bridged spiro-orthoester function and the 4,6-dideoxy-3-O-methyl-Δ3-2-hexosulosyl moiety were elucidated on the basis of spectroscopic data interpretation and chemical transformation. The absolute configurations of the major compounds periplosides C and F were established by single-crystal X-ray diffraction analysis. The isolated compounds were evaluated for their inhibitory activities against the proliferation of T-lymphocytes. As a result, periploside C, the most abundant glycoside containing a spiro-orthoester moiety found in the plant, exhibited the most favorite selective index value (SI = 82.5). The length and constitution of the saccharide chain in the periplosides were found to influence the inhibitory activity and the SI value.


Assuntos
Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Periploca/química , Pregnanos/isolamento & purificação , Pregnanos/farmacologia , Proliferação de Células/efeitos dos fármacos , Glicosídeos/química , Imunossupressores/química , Estrutura Molecular , Raízes de Plantas/química , Pregnanos/química , Linfócitos T/efeitos dos fármacos
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