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1.
Eur J Med Chem ; 185: 111833, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734024

RESUMO

Herein we present and describe the design and synthesis of novel phenantrene derivatives substituted with either amino or amido side chains and their biological activity. Antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity against cancer cells in comparison with 5-fluorouracile. Among all tested compounds, some compounds substituted with cyano groups showed a pronounced and selective activity in the nanomolar range of inhibitory concentrations against HeLa and HepG2. The strongest selective activity against HeLa cells was observed for acrylonitriles 8 and 11 and their cyclic analogues 15 and 17 substituted with two cyano groups with a corresponding IC50 = 0.33, 0.21, 0.65 and 0.45 µM, respectively. Compounds 11 showed the most pronounced selectivity being almost non cytotoxic to normal fibroblasts. Additionally, mode of biological action analysis was performed in silico and in vitro by Western blot analysis of HIF-1-α relative expression for compounds 8 and 11.


Assuntos
Antineoplásicos/farmacologia , Fenantrenos/farmacologia , Tiofenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Hep G2 , Humanos , Estrutura Molecular , Fenantrenos/síntese química , Fenantrenos/química , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/química , Células Tumorais Cultivadas
2.
Zhongguo Zhong Yao Za Zhi ; 44(21): 4566-4572, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872649

RESUMO

Nowadays,the advantages of traditional Chinese medicine(TCM) for treatment of tumors are increasingly prominent.Triptolide shows wide-spectrum and highly effective anti-tumor activity. Moreover,nano-carrier-based triptolide drug delivery system is more powerful in improving water solubility and pharmacokinetic behavior of the drug,but it is easy to cause toxic and side effects that should not be neglected on human body. Because of tumor vascular heterogeneity and PEGylation dilemma,nanoparticulate drug delivery systems need to overcome multiple physiological and pathological barriers from drug administration to functioning. It is difficult for traditional triptolide nanoparticulate drug delivery systems to achieve active accumulation of nano-drug in tumor tissues and specific drug release in tumor target site solely relying on enhanced permeability and retention effect of solid tumor,limiting their application and clinical transformation in treatment of tumors. Based on the traditional nano-preparation system,the new functionalized nano-drug delivery system further enhances the nano-drug enrichment,penetration and controlled release at the tumor sites,which is of great significance in improving bioavailability,anti-tumor efficacy and reducing the side effects of drugs. In this paper,we summarized and analyzed the researches on new triptolide functionalized nano-drug delivery system from four perspectives,including tumor active targeting,tumor microenvironment response,polymer-drug conjugates,and multidrug co-delivery for tumor treatment,expecting to provide ideas for in-depth research and clinical application of triptolide and some other active anti-tumor TCM ingredients.


Assuntos
Diterpenos/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Fenantrenos/química , Compostos de Epóxi/química , Humanos
3.
J Agric Food Chem ; 67(42): 11752-11757, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31554403

RESUMO

Resveratrol (3,5,4'-trihydroxystilbene) is one of the most abundant polyphenols in red grapes, and red wine represents one of the most important dietary sources of this compound. Although its beneficial properties on human health have been widely investigated over the last 30 years, very little is known about its derivatives. Resveratrol can indeed undergo glycosylation, oligomerization and, upon UV-light exposure, it can isomerize from the trans-to the cis-isomer, which can further cyclize to 2,4,6-trihydroxyphenanthrene (THP). Although the effects of THP on human health are not yet known, being a polycyclic aromatic hydrocarbon, it can be potentially harmful. Because no data about THP occurrence in plant food and beverages are available, a simple procedure based on liquid-liquid extraction and gas chromatography-mass spectrometry has been developed and validated for the simultaneous qualitative and quantitative analysis of trans-resveratrol, cis-resveratrol, and THP in red wine, before and after UV-light exposure.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Fenantrenos/química , Resveratrol/química , Vinho/análise , Vinho/efeitos da radiação , Glicosilação , Isomerismo , Raios Ultravioleta
4.
Chem Pharm Bull (Tokyo) ; 67(11): 1208-1210, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31495803

RESUMO

Co-drug, or mutual-prodrug, is a drug design approach consisting of covalently linking two active drugs so as to improve the pharmacokinetics and/or pharmacodynamics properties of one or both drugs. Co-drug strategy has proven good success in overcoming undesirable properties such as absorption, poor bioavailability, nonspecificity, and gastrointestine tract (GIT) side effects. In this work, we successfully developed a co-drug of 14-hydroxytylophorine, a phenanthroindolizidine derivative with remarkable antiproliferative activity, and dichloroacetate, a known inhibitor of pyruvate dehydrogenase kinase. Dichloroacetate steers tumour cell metabolism from glycolysis back to glucose oxidation, which in turn reverses the Warburg effect and renders tumour cells with a proliferative disadvantage. The obtained co-drugs retained the cytotoxicity of 14-hydroxytylophorine. However, they showed similar unselectivity towards normal cells.


Assuntos
Antineoplásicos/farmacologia , Desenho de Drogas , Indóis/farmacologia , Fenantrenos/farmacologia , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Células CHO , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cricetulus , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Estrutura Molecular , Fenantrenos/síntese química , Fenantrenos/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Solubilidade , Relação Estrutura-Atividade
5.
Phytochemistry ; 167: 112101, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473556

RESUMO

In an effort to identify inhibitors of Chikungunya virus (CHIKV) replication, a systematic study of 594 extracts of plant species originating from the French Guiana plateau region was performed in a virus-cell-based assay for CHIKV assay. The extract obtained from the stem bark of Sagotia racemosa was selected for its potent antiviral activity. Using a classical bioassay-guided procedure, three undescribed degraded diterpenoids, i.e. trigohowilols C and D and trigoflavidol D, as well as trigoxyphin K, stictic acid, hyperhomosekikaic acid and five known flavonoids were isolated. The structures of these compounds were elucidated by extensive NMR spectroscopic data analysis. Although trigohowilols C and D were isolated from the most active fraction they didn't show any antiviral activity. By using the Feature-Based Molecular Networking (FBMN) and Network Annotation Propagation (NAP) workflows, it has been shown that the strong anti-CHIKV activity found for this fraction might be due to the presence of analogues of 12-O-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication identified to date.


Assuntos
Antivirais/isolamento & purificação , Antivirais/farmacologia , Vírus Chikungunya/efeitos dos fármacos , Euphorbiaceae/química , Fenantrenos/isolamento & purificação , Fenantrenos/farmacologia , Ésteres de Forbol/química , Antivirais/química , Vírus Chikungunya/fisiologia , Informática , Fenantrenos/química , Replicação Viral/efeitos dos fármacos , Fluxo de Trabalho
6.
Environ Pollut ; 254(Pt A): 113016, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31400666

RESUMO

Dissolved organic carbon (DOC) has a major influence upon sorption/desorption and transport of hydrophobic organic contaminants (HOCs) in soil environments. However, the molecular mechanisms of DOC sorption and its effects on aged HOC desorption in contaminated soils still remain largely unclear. Here, effects of three different DOC (one from commercial peat and two from biochars produced at 300 °C and 500 °C pyrolysis temperatures, respectively) and oxalate (as a reference) on abiotic desorption behavior of aged phenanthrene from three agricultural soils were investigated. Results showed that desorption of aged phenanthrene from soils was predominantly dependent on soil organic carbon content. The presence of DOC and oxalate resulted in higher desorption of phenanthrene compared to water alone, and the effects were positively related to soil organic carbon content and DOC/oxalate concentration. The facilitating effects of DOC were further increased during the second consecutive desorption, whereas oxalate had no such effect. Ultra-high-resolution Fourier transform-ion cyclotron resonance-mass spectrometry confirmed the molecular fractionation of DOC at the soil-water interface during DOC sorption. Specifically, the DOC molecules with O-rich moieties were preferentially adsorbed, whereas the molecules with phenolic and aromatic structures were selectively retained in the soil solutions through competitive displacement and co-sorption reactions during sorption. The enriched phenyl structures in the retained DOC facilitated its association with phenanthrene in the solutions and thus the release of phenanthrene from the soils. In contrast, oxalate replaced some organic carbon from the soils and thus released the associated phenanthrene into the solutions. Our findings highlight the importance of the molecular composition and structure of DOC for the desorption of phenanthrene in soil-water environments, which may help improve our understanding of the release and transport of organic compounds in the environments.


Assuntos
Modelos Químicos , Fenantrenos/análise , Poluentes do Solo/química , Solo/química , Adsorção , Agricultura , Carbono/química , Poluição Ambiental/análise , Interações Hidrofóbicas e Hidrofílicas , Compostos Orgânicos/análise , Fenantrenos/química , Poluentes do Solo/análise , Temperatura Ambiente , Água/química
7.
Chemosphere ; 236: 124366, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31344624

RESUMO

In this work, for the first time, the nonionic surfactant polyoxyethylene-(20)-sorbitan monooleate (Tween 80, C64H124O26) aided soil washing effluent was treated by enhanced activation of persulfate (PS) using Fe(III)-EDDS (EDDS: ethylenediamine-N, N-disuccinic acid) complexes under simulated solar light irradiation. The performance of this system was followed via the production and reactivity of radical species (SO4-, HO, Cl2-) and degradation of phenanthrene (PHE) used as a model pollutant in soils. Different physico-chemical parameters such as the concentration of reactive species and pH were investigated through the PHE degradation efficiency. The second-order rate constants of the reactions for generated radicals with PHE and Tween 80 in solution were identified through competitive reaction experiments under steady-state conditions and application of nanosecond laser flash photolysis (LFP) as well. A kinetic approach was applied to assess the selectivity and reactivity of photo-generated radicals in aqueous medium in order to explain the observed degradation trends. This work proposes an innovative technology of management of soil washing solutions using Fe(III)-EDDS complexes and solar light for the activation of persulfate.


Assuntos
Compostos Férricos/química , Fenantrenos/química , Solo/química , Energia Solar
8.
Environ Sci Pollut Res Int ; 26(25): 25932-25944, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273663

RESUMO

A natural phenanthrene-degrading consortium CON was inoculated with an exogenous strain Sphingobium sp. (ex Sp. paucimobilis) 20006FA yielding the consortium called I-CON, in order to study ecological interactions into the bacterial community. DGGE and proteomic profiles and analyses by HTS (High-Throughput Sequencing) technologies demonstrated inoculant establishment and changes on CON composition. Inoculation increased degradation efficiency in I-CON and prevented intermediate HNA accumulation. This could be explained not only by the inoculation, but also by enrichment in Achromobacter genus at expense of a decrease in Klebsiella genus. After inoculation, cooperation between Sphingobium and Achromobacter genera were improved, thereby, some competition could have been generated, and as a consequence, species in minor proportion (cheaters), as Inquilinus sp. and Luteibacter sp., were not detected. Sequences of Sphingobium (corresponding to the inoculated strain) did not vary. PICRUSt predicted a network with bacterial phylotypes connected with enzymes, showing functional redundancy in the phenanthrene pathway, with exception of the first enzymes biphenyl-2,3-diol 1,2-dioxygenase and protocatechuate 4,5-dioxygenase that were only encoded in Sphingobium sp. This is the first report where a natural consortium that has been characterized by HTS technologies is inoculated with an exogenous strain in order to study competitiveness and interactions.


Assuntos
Achromobacter/química , Achromobacter/metabolismo , Dioxigenases/metabolismo , Fenantrenos/química , Proteômica/métodos , Sphingomonadaceae/metabolismo , Biodegradação Ambiental , Dioxigenases/química , Sphingomonadaceae/química
9.
Environ Sci Pollut Res Int ; 26(24): 25154-25166, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31256397

RESUMO

This study evaluated an enhancement of simultaneous polycyclic aromatic hydrocarbon (PAH) biodegradation and lipid accumulation by Rhodococcus opacus using biochar derived cheaply from biomass gasification effluent. The chemical, physical, morphological, thermal, and magnetic properties of the cheaply derived biochar were initially characterized employing different techniques, which indicated that the material is easy to separate, recover, and reuse for further application. Batch experiments were carried out to study biochar-aided PAH biodegradation by R. opacus clearly demonstrating its positive effect on PAH biodegradation and lipid accumulation by the bacterium utilizing the synthetic media containing 2-, 3- or 4-ring PAH compounds, at an initial concentration in the range 50-200 mg L-1, along with 10% (w/v) inoculum. An enhancement in PAH biodegradation from 79.6 to 92.3%, 76.1 to 90.5%, 74.1 to 88.2%, and 71.6 to 82.3% for naphthalene, anthracene, phenanthrene, and fluoranthene, respectively, were attained with a corresponding lipid accumulation of 68.1%, 74.2%, 72.4%, and 63% (w/w) of cell dry weight (CDW). From contact angle measurements carried out in the study, enhancement in PAH biodegradation and lipid accumulation due to the biochar was attributed to an improved bioavailability of PAH to the degrading bacterium.


Assuntos
Lipídeos/química , Naftalenos/química , Fenantrenos/química , Hidrocarbonetos Policíclicos Aromáticos/química , Rhodococcus/química , Biodegradação Ambiental , Biomassa , Carvão Vegetal , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Rhodococcus/metabolismo
10.
Environ Sci Pollut Res Int ; 26(26): 27281-27290, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325095

RESUMO

Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy may pose adverse health risk to both the mothers and babies. In the present study, 188 pregnant women of different trimesters were recruited in Guangzhou, south China, and nine hydroxyl PAHs (OH-PAHs) and a biomarker of DNA oxidative damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG), were determined in their urine samples. All OH-PAHs except for 4-hydroxyphenanthrene and 6-hydroxychrysene were found in > 90% samples, with total concentration in the range of 0.52 to 42.9 µg/g creatinine. In general, concentration levels of OH-PAHs in pregnant women were lower than those in general population in the same research area but with higher levels in working women than in housewives. The mean daily intakes of PAHs from dietary estimated by urinary OH-PAHs were 0.021, 0.004, 0.047, and 0.030 µg/kg_bw/day for naphthalene, fluorene, phenanthrene, and pyrene, respectively, which were much lower than the reference doses (20, 30, and 40 µg/kg_bw/day for naphthalene, pyrene, and fluorene, respectively) derived from chronic oral exposure data by the United States Environmental Protection Agency. The low exposure levels of PAHs may be attributed to the traditional dietary taboo of Chinese pregnant women, which is to minimize the consumption of "toxic" food. The concentrations of 8-OHdG (4.67-49.4 µg/g creatinine) were significantly positively correlated with concentrations of several OH-PAHs, such as metabolites of naphthalene, fluorene, and phenanthrene (r = 0.3-0.6). In addition, the concentrations of 8-OHdG were higher in working women than in housewives when exposed to the same levels of PAHs, partly indicating the possible relation between work-related pressure for working women and the oxidative stress.


Assuntos
/química , Biomarcadores/química , Dano ao DNA/genética , Naftalenos/química , Fenantrenos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pirenos/química , Adulto , Biomarcadores/metabolismo , China , Poluentes Ambientais/urina , Feminino , Humanos , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/urina , Gravidez
11.
Molecules ; 24(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340614

RESUMO

Photoreactions of acetonitrile solutions of 3,3-diaryl-1,1-dicyano-2-methylprop-1-enes (1a-c) with allyltrimethylsilane (2) in the presence of phenanthrene as a photoredox catalyst and acetic acid as a proton source formed photoallylation (3) and photoreduction (4) products via photoinduced electron transfer pathways. When (S)-mandelic acid was used as the proton source, the reactions proceeded with 3.4 and 4.8 %ee for formation of 3 and 4, respectively. The results of studies of the effect of aryl ring substituents and several chiral carboxylic acids suggested that the enantioselectivities of the reactions are governed by steric controlled proton transfer in intermediate complexes formed by π-π and OH-π interactions of anion radicals derived from 1a-c and chiral carboxylic acids.


Assuntos
Ácidos Carboxílicos/química , Nitrilos/química , Fenantrenos/química , Prótons , Compostos de Trimetilsilil/química , Ácido Acético/química , Alcenos/química , Ânions , Catálise , Radicais Livres , Hidrogenação , Luz , Processos Fotoquímicos , Estereoisomerismo
12.
Molecules ; 24(11)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181731

RESUMO

Celastrol and triptolide, as the two main bio-activity ingredients in Tripterygium wilfordii, have wide anticancer pharmacological potency, as well as anti-inflammatory and immunosuppression effects. However, they have potential hepatotoxicity and underlying mechanisms of them-induced toxicity mediated by hepatic CYP450s have not been well delineated. In the present study, we accessed the toxic effects and possible mechanism of celastrol and triptolide on primary rat hepatocytes. Models of subdued/enhanced activity of CYP450 enzymes in primary rat hepatocytes were also constructed to evaluate the relationship between the two ingredients and CYP450s. LC-MS/MS was used to establish a detection method of the amount of triptolide in rat hepatocytes. As the results, cell viability, biochemical index, and mitochondrial membrane potential indicated that celastrol and triptolide had toxic potencies on hepatocytes. Moreover, the toxic effects were enhanced when the compounds combined with 1-aminobenzotriazole (enzyme inhibitor) while they were mitigated when combined with phenobarbital (an enzyme inducer). Meanwhile, celastrol could affect the amount of triptolide in the cell. We therefore put forward that increase of triptolide in the cell might be one of the main causes of hepatotoxicity caused by Tripterygium wilfordii.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Diterpenos/toxicidade , Fígado/patologia , Fenantrenos/toxicidade , Tripterygium/química , Triterpenos/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diterpenos/química , Interações de Medicamentos , Compostos de Epóxi/química , Compostos de Epóxi/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/efeitos dos fármacos , Masculino , Fenantrenos/química , Fenobarbital/farmacologia , Ratos Wistar , Triazóis/farmacologia , Triterpenos/química
13.
Molecules ; 24(12)2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31242649

RESUMO

Two new phenanthrenes, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxy-phenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with seven known phenanthrenes (3-9), two bibenzyls (10-12), and a lignan (13). Structures of 1 and 2 were elucidated by analyzing one-dimensional (1D) and two-dimensional (2D)-NMR and High-resolution electrospray ionization mass spectra (HR-ESI-MS) data. The absolute configuration of compound 1 was confirmed by the circular dichroism (CD) spectroscopic method. In cytotoxicity assay using FaDu human hypopharynx squamous carcinoma cell line, compounds 3-6, 8, 10, and 12 showed activities, with IC50 values that ranged from 2.55 to 17.70 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Orchidaceae/química , Fenantrenos/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Hipofaríngeas , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fenantrenos/química , Extratos Vegetais/química , Relação Estrutura-Atividade
14.
Cell Mol Neurobiol ; 39(7): 975-983, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31147851

RESUMO

Exposure to corticosterone attenuates hippocampal CA1 long-term potentiation (LTP) via intracellular Zn2+ dysregulation. Here we report that effusol, a phenanthrene isolated from Chinese medicine Juncus effusus, rescues CA1 LTP attenuated by corticosterone. In vivo microdialysis experiment indicated that both increases in extracellular glutamate induced under perfusion with corticosterone and high K+ are suppressed in the hippocampus by co-perfusion with effusol. Because corticosterone and high K+ also increase extracellular Zn2+ level, followed by intracellular Zn2+ dysregulation, the effect of effusol on both the increases was examined in brain slice experiments. Effusol did not suppress increase in extracellular Zn2+ in the hippocampal CA1 of brain slices bathed in corticosterone, but suppressed increase in intracellular Zn2+, which may be linked with suppressing the increase in extracellular glutamate in vivo. In vivo CA1 LTP was attenuated under perfusion with corticosterone prior to LTP induction, while the attenuation was rescued by co-perfusion with effusol, suggesting that the rescuing effect of effusol is due to suppressing the increase in intracellular Zn2+ in CA1 pyramidal cells. The present study indicates that CA1 LTP attenuated by corticosterone is canceled by effusol, which rescues intracellular Zn2+ dysregulation via suppressing extracellular glutamate accumulation. It is likely that effusol defends the hippocampal function against stress-induced cognitive decline.


Assuntos
Região CA1 Hipocampal/fisiologia , Corticosterona/farmacologia , Espaço Intracelular/metabolismo , Potenciação de Longa Duração/fisiologia , Fenantrenos/farmacologia , Zinco/metabolismo , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Glutamatos/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Fenantrenos/química , Ratos Wistar
15.
J Agric Food Chem ; 67(26): 7274-7280, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31244200

RESUMO

Bioactivity-guided separation led to the isolation of six novel phenanthrenes, spiranthesphenanthrenes A-F (1-6), together with 19 known compounds, including seven phenanthrenes (7-13), one bibenzyl compound (14), five flavonoids (15-16 and 20-22), and six simple phenolic compounds (17-19 and 23-25), from the petroleum ether (PE) and ethyl acetate (EtOAc) extracts of Spiranthes sinensis (Pers.) Ames, an edible medicinal plant named "panlongshen" in Chinese that is popularly used in medicinal foods and herbal teas. The structures of the obtained compounds were identified on the basis of extensive NMR spectroscopy and HR-ESI-MS analyses. The cytotoxicities of the phenanthrenes (1-13), the bibenzyl compound (14) , and the flavonoids (15-16 and 20-22) toward SGC-7901, HepG2, and B16-F10 cell lines were examined in vitro. Compounds 1 and 7 exhibited moderate cytotoxic activities toward all of the selected cancer cell lines, and their IC50 values ranged from 19.0 ± 7.3 to 30.2 ± 5.6 µM. Spiranthesphenanthrene A (1) exhibited higher cytotoxic activity than the positive control cisplatin toward the B16-F10 cell line (IC50 = 19.0 ± 7.3 µM). A wound healing assay revealed the inhibition of the migration of B16-F10 cancer cells in a time- and dose-dependent pattern by treatment with 2.5, 5, and 10 µM solutions of compound 1 for 24 and 48 h, respectively. Western blots revealed that compound 1 obviously increased the level of the E-cadherin protein (an epithelial marker) and decreased the levels of the vimentin and N-cadherin proteins (mesenchymal markers). Furthermore, the level of the transcription factor Snail was also obviously decreased by compound 1 in a dose-dependent manner. Taken together, compound 1 inhibits the migration of B16-F10 cancer cells, which may be closely related to the inhibition of the epithelial-mesenchymal transition. Compound 1 represents a promising drug candidate for the prevention of tumor metastasis.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Orchidaceae/química , Fenantrenos/química , Fenantrenos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Fenantrenos/isolamento & purificação , Extratos Vegetais/isolamento & purificação
16.
Int J Biol Macromol ; 137: 751-760, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31254577

RESUMO

Polysaccharides from fungi are good free radical scavengers. However, there are no enzymes digesting these polysaccharides in the human body, which limits the use of fungal polysaccharides. Therefore, it is of great significance to study the preparation methods of fungal polysaccharides to improve the utilization rate of fungal polysaccharides. In this paper, the acidic polysaccharide of Tremella fuciformis was extracted by boiling and precipitated by ethanol. The total sugar content obtained by freeze-drying after ion exchange chromatography purification was 93.6%. It is mainly composed of mannose, glucuronic acid, xylose and fucose. According to the peak area, the mass ratio of the substance is about 6.8:1:1.5:0.6, which indicates that TFP is a polysaccharide with mannose as its main chain and glucuronic acid, fucose and xylose as well as a small amount of glucose as the branch chain. Molecular weight is 1.86 × 106 Da. The existence of glucuronic acid endows polysaccharides with negative charge in aqueous solution and can be assembled into nanostructures with chitosan. By measuring the swelling property in aqueous, it shows the TFP separated from Tremella fuciformis fruits is suitable for drug controlled release.


Assuntos
Basidiomycota/química , Portadores de Fármacos/química , Carpóforos/química , Polissacarídeos Fúngicos/química , Nanoestruturas/química , Adsorção , Diterpenos/química , Liberação Controlada de Fármacos , Compostos de Epóxi/química , Metais Pesados/química , Peso Molecular , Nanopartículas/química , Fenantrenos/química
17.
Int J Mol Sci ; 20(9)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058819

RESUMO

Very limited information is available about heavy metal-polycyclic aromatic hydrocarbons (PAHs) depollution involving the modified natural material in soil. Using phenanthrene and cadmium (Cd) as model, this study investigated the effect(s) of modified rice straw by a NaOH solution and on PAHs, heavy metal availability, and their interactions. Treatment included chemical contaminant with/without modified/unmodified rice straw. Fourier Transform Infrared (FTIR) analysis revealed that certain functional groups including anionic matters groups, which can a complex with Cd2+, were exposed on the modified rice straw surfaces. Therefore, Cd concentration was significantly reduced by about 60%, 57%, 62.5 %, and, 64% in the root, shoot, CaCl2, diethylenetriaminepentaacetic acid (DTPA), and extractable Cd, respectively. Subsequently, the prediction of the functional profile of the soil metagenome using Clusters Orthologous Groups (COGs) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that the significantly changed individual COGs belonged to the carbohydrate metabolism, ion transports, and signaling (including cytochrome P450s) categories. This indicated that ion transports might be involved in Cd management, while carbohydrate metabolism, including bisphenol, benzoate, ethylbenzene degradation, and cytochrome P450s, were rather involved in phenanthrene metabolism. The exposed functional group might serve as an external substrate, and P450s might serve as a catalyst to activate and initiate phenanthrene metabolism process. These finding offer confirmation that modified straw could promote the reduction of heavy metal and the degradation of PAHs in soil.


Assuntos
Biodegradação Ambiental , Cádmio/química , Cádmio/metabolismo , Oryza , Fenantrenos/metabolismo , Poluentes do Solo/metabolismo , Adsorção , Cádmio/isolamento & purificação , Monitoramento Ambiental , Poluição Ambiental , Oryza/química , Oryza/metabolismo , Fenantrenos/química , Solo/química , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Phytomedicine ; 60: 152938, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078367

RESUMO

BACKGROUND: Tylophorine (TYL) is an alkaloid with antiproliferative action in cancer cells. Vascular smooth muscle cell (VSMC) proliferation and neointima formation contribute to restenosis after percutaneous coronary interventions. HYPOTHESIS/PURPOSE: Our goal was to examine the potential of TYL to inhibit VSMC proliferation and migration, and to dissect underlying signaling pathways. STUDY DESIGN AND METHODS: TYL was administered to platelet-derived growth factor (PDGF-BB)-stimulated, serum-stimulated, quiescent and unsynchronized VSMC of rat and human origin. BrdU incorporation and resazurin conversion were used to assess cell proliferation. Cell cycle progression was analyzed by flow cytometry of propidium iodide-stained nuclei. Expression profiles of proteins and mRNAs were determined using western blot analysis and RT-qPCR. The Click-iT OPP Alexa Fluor 488 assay was used to monitor protein biosynthesis. RESULTS: TYL inhibited PDGF-BB-induced proliferation of rat aortic VSMCs by arresting cells in G1 phase of the cell cycle with an IC50 of 0.13 µmol/l. The lack of retinoblastoma protein phosphorylation and cyclin D1 downregulation corroborated a G1 arrest. Inhibition of proliferation and cyclin D1 downregulation were species- and stimulus-independent. TYL also decreased levels of p21 and p27 proteins, although at later time points than observed for cyclin D1. Co-treatment of VSMC with TYL and MG132 or cycloheximide (CHX) excluded proteasome activation by TYL as the mechanism of action. Comparable time-dependent downregulation of cyclin D1, p21 and p27 in TYL- or CHX-treated cells, together with decreased protein synthesis observed in the Click-iT assay, suggests that TYL is a protein synthesis inhibitor. Besides proliferation, TYL also suppressed migration of PDGF-activated VSMC. In a human saphenous vein organ culture model for graft disease, TYL potently inhibited intimal hyperplasia. CONCLUSION: This unique activity profile renders TYL an interesting lead for the treatment of vasculo-proliferative disorders, such as restenosis.


Assuntos
Alcaloides/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/efeitos dos fármacos , Indolizinas/farmacologia , Fenantrenos/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Alcaloides/administração & dosagem , Alcaloides/química , Animais , Becaplermina/administração & dosagem , Ciclina D1/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Indolizinas/administração & dosagem , Indolizinas/química , Miócitos de Músculo Liso/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Fenantrenos/administração & dosagem , Fenantrenos/química , Ratos , Ratos Sprague-Dawley , Veias Umbilicais
19.
Chem Commun (Camb) ; 55(60): 8764-8767, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31139806

RESUMO

Ru(ii)-complexes with polyazaaromatic ligands can undergo direct electron transfer with guanine nucleobases on blue light excitation that results in DNA lesions with phototherapeutic potential. Here we use single molecule approaches to demonstrate DNA binding mode heterogeneity and evaluate how multivalent binding governs the photochemistry of [Ru(TAP)3]2+ (TAP = 1,4,5,8-tetraazaphenanthrene).


Assuntos
DNA/química , Substâncias Intercalantes/química , Compostos Organometálicos/química , Fenantrenos/química , Adutos de DNA/síntese química , Guanina/química , Substâncias Intercalantes/efeitos da radiação , Ligantes , Luz , Conformação de Ácido Nucleico , Compostos Organometálicos/efeitos da radiação , Fenantrenos/efeitos da radiação , Fenantrolinas/química , Fenantrolinas/efeitos da radiação , Rutênio/química
20.
Am J Chin Med ; 47(4): 769-785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31091976

RESUMO

Tripterygium wilfordii Hook F. (TWHF), a traditional Chinese medicine, has been widely used to treat autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis in China. Recently, studies have demonstrated that the bioactive components of TWHF have effective therapeutic potential for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Multiple Sclerosis. In this paper, we summarize the research progress of triptolide and celastrol (the two major TWHF components) as well as their analogues in the treatment of neurodegenerative diseases. In addition, we review and discuss the molecular mechanisms and structure features of those two bioactive TWHF components, highlighting their therapeutic promise in neurodegenerative diseases.


Assuntos
Diterpenos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Fenantrenos/uso terapêutico , Fitoterapia , Tripterygium/química , Triterpenos/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Compostos de Epóxi/química , Compostos de Epóxi/isolamento & purificação , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Conformação Molecular , Fármacos Neuroprotetores , Doença de Parkinson/tratamento farmacológico , Fenantrenos/química , Fenantrenos/isolamento & purificação , Fenantrenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
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