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1.
Anticancer Res ; 40(9): 5015-5024, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878789

RESUMO

BACKGROUND/AIM: Despite being a rare disease, melanoma is considered the most dangerous skin cancer due to its highly invasive and aggressive nature, and still requires for more effective treatments. The aim of this study was to evaluate the in vitro anti-melanoma potential of Ephedranthus pisocarpus R.E.Fr. (Annonaceae), a popular Brazilian plant with medicinal properties. MATERIALS AND METHODS: Initially, the ethanolic extract (EtOH) was obtained from E. pisocarpus leaves and later partitioned using increasing polarity solvents. The anti-melanoma potential of E. pisocarpus was assessed by spectrophotometry and its cytotoxicity determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and confocal microscopy. RESULTS: We demonstrated that the EtOH extract and fractions from E. pisocarpus had a moderate photoprotective action (FPS 3.0-5.0) against UVA radiation. Interestingly, the dichloromethane fraction presented higher anti-melanoma activity against B16-F10 (IC50=46.8 µg/ml) and SK-MEL-28 cells (IC50=40.1 µg/ml) and lesser toxicity on normal cells. Additionally, our study reported that spathulenol, one of the major constituents from E. pisocarpus, acts through an apoptosis-dependent mechanism in SK-MEL-28 cells. CONCLUSION: The present study demonstrated, for the first time, the in vitro anti-melanoma potential of E. pisocarpus against melanoma cells.


Assuntos
Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Brasil , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citotoxicidade Imunológica , Relação Dose-Resposta a Droga , Hemólise , Humanos , Melanoma Experimental , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
2.
Anticancer Res ; 40(9): 5201-5210, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878808

RESUMO

BACKGROUND/AIM: Persimmon (Diospyros kaki L.) leaves are popular as a tea infusion in Asia and their main active ingredients are flavonoids. The present study aimed to explore the anticancer properties of flavonoids isolated from persimmon leaves (PLF). MATERIALS AND METHODS: We investigated the in vitro anti-proliferative activity of PLF against several human cancer cell lines. Apoptosis and intracellular reactive oxygen species (ROS) induced by PLF were accessed using high-content analysis with florescent staining. The ability of PLF to scavenge free radicals was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: PLF demonstrated significant inhibition of proliferation of liver, breast, and colorectal cancer cells in vitro. PLF induced apoptosis and increased intracellular ROS levels in HCT116 (colorectal cancer) and HepG2 (liver cancer) cells. In addition, PLF showed strong free radical scavenging ability. CONCLUSION: The anti-proliferation activity of PLF against cancer cells was related to the induction of apoptosis and oxidative stress.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diospyros/química , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo
3.
Environ Toxicol ; 35(10): 1058-1069, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32485087

RESUMO

Glioblastoma is the most common primary brain tumor with poor survival rate and without effective treatment strategy. Notably, amplification and active mutation of epidermal growth factor receptor (EGFR) occur frequently in glioblastoma patient that may be a potential treatment target. Several studies indicated that various type of herbal compounds not only regulate anti-depressant effect but also shown capacity to suppress glioblastoma growth via inducing apoptosis and inhibiting oncogene signaling transduction. Hyperforin, an herb compound derived from St. John's wort was used to treat depressive disorder by inhibiting neuronal reuptake of several neurotransmitters. Although hyperforin can reduce matrix metallopeptidases-2 (MMPs) and -9-mediated metastasis of glioblastoma, the detail mechanism of hyperforin on glioblastoma is remaining unclear. Here, we suggested that hyperforin may induce extrinsic/intrinsic apoptosis and suppress anti-apoptotic related proteins expression of glioblastoma. We also indicated that hyperforin-mediated anti-apoptotic potential of glioblastoma was correlated to inactivation of EGFR/extracellular signal-regulated kinases (ERK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Floroglucinol/análogos & derivados , Terpenos/farmacologia , Fator de Transcrição RelA/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Hypericum/química , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , Transdução de Sinais , Terpenos/isolamento & purificação , Fator de Transcrição RelA/genética
4.
Environ Toxicol ; 35(10): 1125-1136, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32449848

RESUMO

This study aimed to evaluate the in vivo anticancer effects of daucosterol which was earlier reported to possess in vitro anticancer effects. Breast tumor was induced in 30 rats using the environmental carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) while 6 control rats received olive oil (NOR). Animals with palpable tumors were randomized into five groups (n = 6) each as follows: negative control group treated with the vehicle (DMBA); positive control group treated with 5 mg/kg BW doxorubicin (DOXO + DMBA); three groups treated with daucosterol at doses of 2.5, 5, and 10 mg/kg BW (DAU + DMBA). Treatment lasted 28 days afterward, tumor (mass, volume, cancer antigen [CA] 15-3 level and histoarchitecture), hematological and toxicological parameters were examined. The tumor volume gradually increased in the DMBA group during the 28 days, with a tumor volume gain of ∼390 cm3 . Daucosterol at all doses reduced tumor volume (∼133.7 cm3 at 10 mg/kg) as well as protein, malondialdehyde (MDA), and CA 15-3 levels compared to DMBA rats. Tumor sections in daucosterol-treated rats showed a lower proliferation of mammary ducts with mild (5 and 10 mg/kg) to moderate (2.5 mg/kg) inflammatory responses. Moreover, it exhibited an antioxidant effect, evidenced by a significant and dose-dependent decreased in MDA levels, as well as an increase in catalase activity compared to the DMBA group. Daucosterol showed for the first time in vivo antitumor effects that corroborate its previous in vitro effects.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Capparaceae/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Sitosteroides/farmacologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/metabolismo , Carcinógenos/toxicidade , Relação Dose-Resposta a Droga , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Estrutura Molecular , Casca de Planta/química , Ratos , Ratos Wistar , Sitosteroides/isolamento & purificação , Sitosteroides/uso terapêutico
5.
PLoS One ; 15(5): e0231437, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357169

RESUMO

As a traditional Chinese medicine, Croton tiglium has the characteristics of laxative, analgesic, antibacterial and swelling. This study aimed to analyze the chemical composition of C. tiglium essential oil (CTEO) extracted from the seeds of C. tiglium and its cytotoxicity and antitumor effect in vitro. Supercritical CO2 fluid extraction technology was used to extract CTEO and the chemical constituents of the essential oil were identified by comparing the retention indices and mass spectra data taken from the NIST library with those calculated based on the C7-C40 n-alkanes standard. In vitro cytotoxicity of the CTEO was assessed against cancer cell lines (A549) and the human normal bronchial epithelial cells (HBE) using the CCK-8 assay. Proliferation was detected by colony formation experiments. Wound scratch and cell invasion assays were used to detect cell migration and invasion. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. As the results, twenty-eight compounds representing 92.39% of the total oil were identified in CTEO. The CTEO has significant antitumor activity on A549 cancer cells (IC50 48.38 µg/mL). In vitro antitumor experiments showed that CTEO treatment significantly inhibited the proliferation and migration of A549 cells, disrupted the cell cycle process, and reduced the expression levels of cyclin A, cyclin B and CDK1. CTEO can also reduce mitochondrial membrane potential, activate caspase-dependent apoptosis pathway, and finally induce apoptosis. CTEO may become an effective anti-cancer drug and will be further developed for cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose , Proliferação de Células , Croton/química , Neoplasias Pulmonares/tratamento farmacológico , Óleos Voláteis/farmacologia , Células A549 , Antineoplásicos Fitogênicos/isolamento & purificação , Ciclo Celular , Movimento Celular , Cromatografia com Fluido Supercrítico , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial , Óleos Voláteis/isolamento & purificação , Transdução de Sinais
6.
Int J Exp Pathol ; 101(3-4): 106-121, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32452573

RESUMO

Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF-7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization-ion trap tandem mass spectrometry analysis (FIA-ESI-IT-MSn ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross-sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma-bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Florestas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Melanoma Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Solanaceae/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Neoplasias da Mama/patologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Células MCF-7 , Melanoma Experimental/secundário , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Metástase Neoplásica , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química
7.
Biochim Biophys Acta Proteins Proteom ; 1868(8): 140440, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32376479

RESUMO

Lunasin is a 43-amino acid peptide from seeds and grains with bioavailability in humans and potent chemotherapeutic action against several cancer cell lines. Here, we investigate new information about the physicochemical and structural properties of lunasin using circular dichroism (CD), fluorescence spectroscopy, electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS), size exclusion chromatography (SEC), molecular dynamics (MD), and bioinformatics. CD analysis and disorder prediction obtained by PONDR indicate that lunasin has a mostly unordered structure. Double wavelength [θ]222nm x [θ]200nm plot data suggests that lunasin is an intrinsically disordered peptide (IDP) in a pre-molten globule-like (PMG-like) state, while CD spectrum deconvolution and MD simulation indicate small ß-strand content. The presence of residual structure was supported by loss of CD signal at 222 nm after treatment with urea and by increasing fluorescence emission upon bis-ANS binding. Lunasin also demonstrated stability to heating up to the temperature of 100 °C, as verified by CD. MD and CD analyses in the presence of TFE and MoRFpred prediction indicated the helix propensity of lunasin. ESI-IMS-MS data revealed that lunasin shows a propensity to form disulfide bonds at the conditions used. MD data also indicated that disulfide bond formation affects the adopted structure, showing a possible role of aspartyl-end in structure stabilization and compaction. In conclusion, our data support a characterization of lunasin as a peptide with an intrinsic disorder in a PMG-like state and reveal new aspects about its structural stability and plasticity, as well as the effects of disulfide bond formation and electrostatic attractions.


Assuntos
Antineoplásicos Fitogênicos/química , Proteínas Intrinsicamente Desordenadas/química , Proteínas de Soja/química , Sequência de Aminoácidos , Antineoplásicos Fitogênicos/isolamento & purificação , Dissulfetos , Humanos , Proteínas Intrinsicamente Desordenadas/isolamento & purificação , Simulação de Dinâmica Molecular , Dobramento de Proteína , Estabilidade Proteica , Estrutura Secundária de Proteína , Proteínas de Soja/isolamento & purificação , Soja/química , Espectrometria de Fluorescência , Espectrometria de Massas por Ionização por Electrospray , Temperatura , Ureia/química
8.
Curr Pharm Biotechnol ; 21(11): 1028-1041, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297580

RESUMO

BACKGROUND: Cancer is the leading cause of death worldwide and the current mode of cancer treatment causes side effects on normal cells and are still the key challenges in its' treatment. However, natural products or active compounds of medicinal plants have shown to be safe, affordable, and effective in diseases cure. METHODS: In this context, scientific studies evidence the health-promoting effects of natural products, which work through its anti-oxidant, anti-inflammatory, and anti-cancer activity. Thymoquinone (TM), a predominant active compound of Nigella sativa, has confirmed anti-neoplastic activity through its ability to regulate various genetic pathways. In addition, thymoquinone has established anti-cancerous effects through killing of various cancerous cells,and inhibiting the initiation, migration, invasion, and progression of the cancer. The anti-cancer effects of TM are chiefly mediated via regulating various cell signaling pathways such as VEGF, bcl2/bax ratio, p53, NF-kB, and oncogenes. RESULTS: The anti-cancer drugs have limitations in efficacy and also causes adverse side effects on normal cells. The combination of anti-cancer drugs and thymoquinone improves the efficacy of drugs which is evident by decrease resistance to drugs and regulation of various cell signaling pathways. Moreover, combination of anti-cancer drugs as well as thymoquinone shows synergistic effect on killing of cancer cells and cells viability. Thus, TM, in combination with anti-cancer drugs, can be a good strategy in the management of various types of cancer. CONCLUSION: In this review article, we deliver an outline of thymoquinone role in cancer inhibition and prevention of cancer-based on in vivo and in vitro studies. Further studies on thymoquinone based on clinical trials are highly required to explore the benefits of thymoquinone in cancer management.


Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Benzoquinonas/farmacologia , Nigella sativa/química , Anticarcinógenos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Benzoquinonas/isolamento & purificação , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Transdução de Sinais/efeitos dos fármacos
9.
Chem Pharm Bull (Tokyo) ; 68(3): 273-287, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115535

RESUMO

Phytochemical analysis of the whole Helleborus foetidus plants identified 28 steroidal glycosides (1-28), including 20 novel spirostanol glycosides (1-20) and a novel furostanol glycoside (21). The structures of the newly identified compounds were elucidated by two-dimensional NMR spectroscopy and hydrolytic cleavage. Compounds 12, 13, and 15 were determined to be spirostanol trisdesmosides bearing sugar moieties at the C-1, -21, and -24 hydroxy groups of the aglycone unit. The isolated compounds were subsequently evaluated for cytotoxic activity against HL-60 human promyelocytic leukemia cells and A549 human lung carcinoma cells. In particular, 7 showed cytotoxic activity against the HL-60 and A549 cells, with IC50 values of 5.9 and 6.6 µM, respectively, whereas 19 was selectively cytotoxic to A549 cells with an IC50 value of 5.5 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Glicosídeos/farmacologia , Helleborus/química , Compostos Fitoquímicos/farmacologia , Esteroides/farmacologia , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Células HL-60 , Humanos , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
10.
Chem Pharm Bull (Tokyo) ; 68(3): 244-250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115531

RESUMO

Aspidosperma alkaloids, a subclass of monoterpenoid indole alkaloids rich in the Apocynaceae plants, possess remarkable antitumor activities, but the underlying mechanisms have rarely been reported. In the current project, 11-methoxytabersonine (11-MT), an aspidosperma-type alkaloid isolated from Tabernaemontana bovina, significantly inhibited the viability of two human lung cancer cell lines A549 and H157, and the molecular mechanisms were thus investigated. The results showed that 11-MT killed lung cancer cells via induction of necroptosis in an apoptosis-independent manner. In addition, 11-MT strongly induced autophagy in the two cell lines, which played a protective role against 11-MT-induced necroptosis. Finally, the autophagy caused by 11-MT was found to be via activation of the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and the c-Jun N-terminal kinase (JNK) signaling pathways in both cells. Taken together, 11-MT exhibited an antitumor mechanism different from that of previously reported analogues and could have the potential to serve as a lead compound for the development of new chemotherapy for lung cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Monoterpenos/farmacologia , Necroptose/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Tabernaemontana/química , Células A549 , Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/isolamento & purificação , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Monoterpenos/isolamento & purificação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo
11.
Phytochemistry ; 171: 112228, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31911265

RESUMO

A previously undescribed taraxerene-type triterpenoid possessing a class of rare natural taraxerene triterpenoid possessing skeleton with 14, 28-lactone, two undescribed oleane-type triterpenoids, and twenty-five known triterpenoids were isolated from Liquidambar formosana (Hamamelidaceae). The structures of undescribed compounds were determined on the basis of 1D and 2D NMR spectroscopic, HR-ESI-MS, and X-ray crystallographic data analysis. Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13ß-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 µM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 µM). Mechanism studies suggested that these three compounds could regulate the mitochondrial pathway by up-regulating the expressions of pro-apoptotic factors (Bad and Bax) and activating caspase-3 and caspase-9 to induce apoptosis. Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Liquidambar/química , Compostos Fitoquímicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/química , Triterpenos/isolamento & purificação , Células Tumorais Cultivadas
12.
Phytochemistry ; 171: 112248, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31918304

RESUMO

The phytochemical investigation of the twig and leaf extracts of Goniothalamus tamirensis led to the isolation and identification of 15 compounds including three rare previously undescribed styryllactones, goniotamirenones A-C, together with 12 known compounds. (Z)-6-Styryl-5,6-dihydro-2-pyranone and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one are reported here for the first time as previously undescribed natural products. Their structures were elucidated by spectroscopic methods. Goniotamirenone A was synthesized via a [2 + 2] cycloaddition reaction of 6-styrrylpyran-2-one in quantitative yield. The absolute configurations of goniotamirenones B and C were identified from experimental and calculated ECD data, while the absolute configurations of (-)-5-acetoxygoniothalamin, (-)-isoaltholactone, parvistone E, and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one were identified by single-crystal X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of the other related compounds were determined from comparisons of their ECD spectra with relevant compounds reported in the literature. (-)-5-Acetoxygoniothalamin exhibited potent cytotoxicity against the colon cancer cell line (HCT116) with an IC50 value of 8.6 µM which was better than the standard control (doxorubicin, IC50 = 9.7 µM), while (Z)-6-styryl-5,6-dihydro-2-pyranone was less active with an IC50 value of 22.1 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Goniothalamus/química , Lactonas/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Estirenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Modelos Moleculares , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Estirenos/química , Estirenos/isolamento & purificação
13.
Chem Biodivers ; 17(1): e1900638, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31908155

RESUMO

Starfishes produce various structurally unique secondary metabolites with diverse biological activities. This review is an update summary of the new compounds and their bioactivities from starfish (the Asteroidea Class) with 71 references covering from January 2007 to December 2018. During this period, 216 new compounds were obtained from 36 species. The chemical constituents are mostly steroids, steroidal glycosides, and gangliosides. These components have been found to possess various bioactivities, including anticancer, anti-inflammation, etc.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Estrelas-do-Mar/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Humanos
14.
Molecules ; 25(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947862

RESUMO

The seeds of Millettia ferruginea are used in fishing, pesticides, and folk medicine in Ethiopia. Here, the anti-cancer effects of isoflavones isolated from M. ferruginea were evaluated in human ovarian cancer cells. We found that isoflavone ferrugone and 6,7-dimethoxy-3',4'-methylenedioxy-8-(3,3-dimethylallyl)isoflavone (DMI) had potent cytotoxic effects on human ovarian cancer cell A2780 and SKOV3. Ferrugone and DMI treatment increased the sub-G1 cell population in a dose-dependent manner in A2780 cells. The cytotoxic activity of ferrugone and DMI was associated with the induction of apoptosis, as shown by an increase in annexin V-positive cells. Z-VAD-fmk, a broad-spectrum caspase inhibitor, and z-DEVD-fmk, a caspase-3 inhibitor, significantly reversed both the ferrugone and DMI-induced apoptosis, suggesting that cell death stimulated by the isoflavones is mediated by caspase-3-dependent apoptosis. Additionally, ferrugone-induced apoptosis was found to be caspase-8-dependent, while DMI-induced apoptosis was caspase-9-dependent. Notably, DMI, but not ferrugone, increased the intracellular levels of reactive oxygen species (ROS), and antioxidant N-acetyl-L-cysteine (NAC) attenuated the pro-apoptotic activity of DMI. These data suggest that DMI induced apoptotic cell death through the intrinsic pathway via ROS production, while ferrugone stimulated the extrinsic pathway in human ovarian cancer cells.


Assuntos
Antineoplásicos Fitogênicos , Apoptose/efeitos dos fármacos , Isoflavonas , Millettia/química , Neoplasias Ovarianas/tratamento farmacológico , Sementes/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular , Feminino , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia
15.
Curr Pharm Biotechnol ; 21(9): 842-851, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995002

RESUMO

BACKGROUND: Estrogen Receptors (ER) are members of the nuclear intracellular receptors family. ER once activated by estrogen, it binds to DNA via translocating into the nucleus and regulates the activity of various genes. Withaferin A (WA) - an active compound of a medicinal plant Withania somnifera was reported to be a very effective anti-cancer agent and some of the recent studies has demonstrated that WA is capable of arresting the development of breast cancer via targeting estrogen receptor. OBJECTIVE: The present study is aimed at understanding the molecular level interactions of ER and Tamoxifen in comparison to Withaferin A using In-silico approaches with emphasis on Withaferin A binding capability with ER in presence of point mutations which are causing de novo drug resistance to existing drugs like Tamoxifen. METHODS: Molecular modeling and docking studies were performed for the Tamoxifen and Withaferin A with the Estrogen receptor. Molecular docking simulations of estrogen receptor in complex with Tamoxifen and Withaferin A were also performed. RESULTS: Amino acid residues, Glu353, Arg394 and Leu387 was observed as crucial for binding and stabilizing the protein-ligand complex in case of Tamoxifen and Withaferin-A. The potential of Withaferin A to overcome the drug resistance caused by the mutations in estrogen receptor to the existing drugs such as Tamoxifen was demonstrated. CONCLUSION: In-silico analysis has elucidated the binding mode and molecular level interactions which are expected to be of great help in further optimizing Withaferin A or design / discovery of future breast cancer inhibitors targeting estrogen receptor.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/metabolismo , Receptores Estrogênicos/antagonistas & inibidores , Withania/química , Vitanolídeos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Simulação por Computador , Humanos , Ligantes , Simulação de Acoplamento Molecular , Plantas Medicinais , Mutação Puntual , Ligação Proteica , Receptores Estrogênicos/genética , Vitanolídeos/isolamento & purificação
16.
Phytochemistry ; 171: 112231, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901473

RESUMO

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii.


Assuntos
Compostos Fitoquímicos/farmacologia , Thymelaeaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
17.
Phytochemistry ; 171: 112237, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901475

RESUMO

Four undescribed alkaloids, namely collacyclumines A-D, along with a known analogue, agrocybenine, were isolated from the endophytic fungus Colletotrichum salsolae SCSIO 41021 derived from the mangrove plant Kandelia candel (L.) Druce. Collacyclumine A represents the first case of dimeric pyrrolidine alkaloid in nature. The structures of these compounds were elucidated by a combination of NMR spectra, HRESIMS data, and X-ray diffraction experiment. A proposed biosynthetic pathway of these isolated compounds were also discussed. None of compounds showed cytotoxic effects against ten cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Colletotrichum/química , Compostos Fitoquímicos/farmacologia , Rhizophoraceae/microbiologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Colletotrichum/citologia , Colletotrichum/metabolismo , Cristalografia por Raios X , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
18.
Fitoterapia ; 140: 104432, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759030

RESUMO

Seven new lignans, cleistonkinins A- E (1-5), cleistonkisides A and B (6-7) were isolated from the fruits of Cleistanthus tonkinensis (Euphorbiaceae), together with five known aryltetralin lignans, cleisindoside B (8), cleistantoxin (9), cleisindoside D (10), neocleistantoxin (11) and polygamain (12). Their structures were established from spectral analysis, including mass spectrometry and 2D-NMR. The absolute configurations of 4-7 were determined by analysis of their experimental CD spectra and comparison with calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 6 had selective inhibition with moderate cytotoxicity against Pan C1 and A549 cell lines, respectively. Cleistantoxin (9) was significantly active against A549, HeLa, Hep3B, Pan C1 and MCF7 cell lines while it was less cytotoxic against HeLa cells. Neocleistantoxin (11) exhibited remarkable inhibition toward A549, HeLa, MCF7 and Pan C1. This is the first report for cytotoxicity of 9 and 11 against A549, Hep3B and Pan C1 cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Euphorbiaceae/química , Frutas/química , Lignanas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Lignanas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Vietnã
19.
Fitoterapia ; 140: 104431, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759031

RESUMO

Two novel heptanornemoralisin-type diterpenoids nornemoralisins A (1) and B (2), together with two known compounds nemoralisin (3) and nemoralisin A (4), were isolated from the stem bark and leaves of Aphanamixis polystachya (Wall.) R. Parker. Their structures were established through comprehensive analyses of NMR spectroscopic data and high resolution mass spectrometric (HR-ESI-MS) data. The absolute configurations of carbon stereocenters were elucidated by circular dichroism (CD) analyses. The four compounds were tested for their potential cytotoxic effects against ACHN, HeLa, SMMC-7721, and MCF-7 cell lines. Nornemoralisins A (1) and B (2) exhibited significant cytotoxicity on ACHN with an IC50 value of 13.9 ± 0.8 and 10.3 ± 0.4 µM, respectively, and other compounds failed to reveal obvious cytotoxicity on the tested cell lines, compared to positive control vinblastine (IC50, 28.0 ± 0.9 µM).


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Meliaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , China , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Folhas de Planta/química
20.
Phytochemistry ; 170: 112201, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31778881

RESUMO

Nine undescribed triterpenoids (jughopenoids A-I), including seven nortriterpenoids and two normal triterpenoids, together with fourteen known analogues, were isolated from the barks of Juglans hopeiensis Hu. The structures of the undescribed triterpenoids were established by integrated spectroscopic analysis and single crystal X-ray diffraction. Jughopenoid A represented an unprecedented lupane-type nortriterpenoid with a five-membered lactone ring A. Selected isolates were tested for their cytotoxic effects against human HT-29 colon carcinoma, human HepG2 hepatocellular carcinoma, and human PC-3 prostate cancer cell lines. Their immunosuppressive activities against ConA-induced T cell proliferation and LPS-induced B cell proliferation were also evaluated.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Juglans/química , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Células Hep G2 , Humanos , Modelos Moleculares , Estrutura Molecular , Células PC-3 , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação
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