Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.699
Filtrar
1.
PLoS One ; 15(6): e0235131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569333

RESUMO

BACKGROUND: Residual contamination by intravenous conventional antineoplastic drugs (ICAD) is still a daily issue in hospital facilities. This study aimed to compare the efficiency (EffQ) of 4 different solutions to remove 23 widely used ICADs from surfaces. METHOD AND FINDINGS: A solution containing 23 ICADs (4 alkylating agents, 8 antimetabolites, 2 topo-I inhibitors, 6 topo-II inhibitors and 3 spindle poisons) was spread over 100 cm2 stainless steel. After drying, decontamination was carried out using 10×10 cm wipes moistened with 300 µL of one of the following solutions: 70% isopropanol (S1); ethanol-hydrogen peroxide 91.6-50.0 mg/g (S2); 10-2 M sodium dodecyl sulphate/isopropanol 80/20 (S3) or 0.5% sodium hypochlorite (S4). Six tests were performed for each decontamination solution. Two modalities were tested: a single wipe motion from top to bottom or vigorous wiping (n = 6 for each modality). Residual contamination was measured with a validated liquid chromatography with tandem mass spectrometry detection method. Solution efficiency (in %) was computed as follows: EffQ = 1-(quantity after decontamination/quantity before decontamination), as median (min-max) for the 23 ICADs. The overall decontamination efficiency (EffQ) of the 4 solutions was compared by a Kruskall-Wallis test. Decontamination modalities were compared for each solution and per ICAD with a Mann-Whitney test (p<0.05). EffQ were significantly different from one solution to the next for single wipe motion decontamination: 79.9% (69.3-100), 86.5% (13.0-100), 85.4% (56.5-100) and 100% (52.9-100) for S1, S2, S3 and S4 (p<0.0001), respectively. Differences were also significant for vigorous decontamination: EffQ of 84.3% (66.0-100), 92.3% (68.7-100), 99.6% (84.8-100) and 100% (82.9-100) for S1, S2, S3 and S4, respectively (p<0.0001). Generally, vigorous decontamination increased EffQ for all tested solutions and more significantly for the surfactant. CONCLUSION: Decontamination efficiency depended on the solution used but also on the application modality. An SDS admixture seems to be a good alternative to sodium hypochlorite, notably after vigorous chemical decontamination with no hazard either to materials or workers.


Assuntos
Antineoplásicos/isolamento & purificação , Descontaminação , Contaminação de Medicamentos , Soluções , Aço Inoxidável , Propriedades de Superfície
2.
Anticancer Res ; 40(5): 2549-2557, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366399

RESUMO

BACKGROUND/AIM: Sonodynamic cancer therapy is based on the preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and the subsequent activation of the drug by ultrasound irradiation. In the present study, we investigated the sonodynamically-induced antitumoral effect with functionalized carbon nanotubes, such as poly-ethylene glycol-modified carbon nanotubes (PEG-modified CNTs). MATERIALS AND METHODS: Antitumor effects were evaluated using histological observation and assessing tumor growth following sonodynamic exposure to PEG-modified CNTs. RESULTS: The combined treatment of 100 µM PEG-modified CNT and ultrasound induced a 2-fold cytotoxicity. Sodium azide, which quenches singlet oxygen, significantly inhibited ultrasonication induced cell damage in the presence of PEG-modified CNTs. This suggests that singlet oxygen produced by the combined use of PEG-modified CNTs and ultrasound is involved in the induction of antitumoral effects. The destruction of tumor tissue was observed with the ultrasonic treatment in combination with PEG-modified CNTs, while neither the treatment with PEG-modified CNTs alone nor ultrasound alone caused any necrosis. CONCLUSION: These results indicate that PEG-modified CNT functions as a sonosensitizer and is effective for sonochemical treatment of solid tumors.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Nanotubos de Carbono , Polietilenoglicóis , Ondas Ultrassônicas , Animais , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Estrutura Molecular , Nanotubos de Carbono/química , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/metabolismo , Sarcoma 180 , Terapia por Ultrassom , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Chromatogr A ; 1621: 461053, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32276857

RESUMO

The chromatographic properties of a new coated amylose tris(3-chloro-5-methylphenylcarbamate) were evaluated in supercritical fluid chromatography for the separation of enantiomers of chiral 1-aryl-5-aryl-pyrrolidin-2-one derivatives, potential anticancer agents, and some commercial drugs. The mobile phase consisted of CO2-modifier mixtures with 30% of either methanol or ethanol, the flow rate was 3 mL/min. The column oven temperature was 40 °C and the outlet pressure was 15 MPa, in order to limit the compressibility of the CO2, thus limiting density variation along the column. The obtained results were then compared to those observed toward 3 other stationary phases: the coated amylose tris(3,5-dimethylphenylcarbamate), the immobilized amylose tris(3,5-dimethylphenylcarbamate) and the coated amylose tris(5-chloro-2-methylphenylcarbamate). It was shown that the new coated amylose tris(3-chloro-5-methylphenylcarbamate) was the most retentive column whatever the studied compounds, particularly for thalidomide and omeprazole with retention factors up to 73.3 and 29.5for the second enantiomer, respectively. Concerning the enantioselectivity, even most of the compounds are separated on all the four columns, the coated amylose tris(3-chloro-5-methylphenylcarbamate) allows the best resolution for most of the ten studied analytes (except omeprazole for which the resolution values are equal to 7.8 and 9.7 on the coated amylose tris(3-chloro-5-methylphenylcarbamate) and amylose tris(3,5-dimethylphenylcarbamate), respectively). Acting in complementary ways, the two chlorinated stationary phases permitted the complete separation of enantiomers of nine compounds out of the ten.


Assuntos
Amilose/análogos & derivados , Cromatografia com Fluido Supercrítico/métodos , Amilose/química , Antineoplásicos/análise , Antineoplásicos/isolamento & purificação , Carbamatos/química , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/isolamento & purificação , Fenilcarbamatos/química , Pirrolidinonas/análise , Pirrolidinonas/isolamento & purificação , Dióxido de Silício/química , Estereoisomerismo
4.
J Nat Med ; 74(3): 584-590, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32207026

RESUMO

Three new 5,6-dihydro-α-pyrones derivatives, named (S)-rugulactone (1) pulchrinervialactone A (2), and pulchrinervialactone B (4), along with one known pyrone, cryptobrachytone C (3), and three known amide derivatives (5-7) have been isolated from the leaves of Cryptocarya pulchrinervia. The structures of 1-7 were elucidated based on extensive spectroscopic data and comparison with literatures. The configurations of compounds 3 and 4 were established by single crystal X-ray diffraction analysis. This is also the first report in finding (S)-rugulactone (1) as a natural product. In addition, the preliminary cytotoxic activity of the isolated compounds was evaluated against P-388 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. All the pyrones, except compound 4, were active significantly inhibiting the growth of P-388 cells, while the amides derivatives (5-7) showed moderate to weak activities. Therefore, compounds 1-3 could be potentially examined further for anticancer agents.


Assuntos
Antineoplásicos/farmacocinética , Proliferação de Células/efeitos dos fármacos , Cryptocarya/química , Lactonas/farmacologia , Pironas/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Lactonas/isolamento & purificação , Camundongos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Folhas de Planta/química , Pironas/isolamento & purificação
5.
J Appl Microbiol ; 129(2): 356-366, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32119169

RESUMO

AIMS: Utilization of l-asparaginase has been one of the effective strategies for the treatment of lymphoblastic leukaemia. Since the currently used bacterial l-asparaginase causes side effects, searching for new enzyme sources has been an active field of research. This study focuses on the characterization of an l-asparaginase-producing fungal strain. METHODS AND RESULTS: Sarocladium strictum was identified as a potent enzyme-producing strain. For the enhancement of enzyme production, we used two-level factorial design and response surface methodology. The optimization of significant factors showed a 1·84-fold increase in enzyme production. The Km and Vmax values of the enzyme were 9·74 mmol l-1 and 8·19 µmol min-1 . The toxicity of the produced l-asparaginase was measured on K562 and HL60 cancer cell lines and L6 as normal cells. The IC50 values were calculated as 0·4 and 0·5 IU ml-1 for K562 and HL60 respectively and no significant effect was observed in L6. BrdU proliferation and caspase-3 activity assay in l-asparaginase treated HL60 and K562 cells indicated that cell proliferation rates and apoptotic cell death were reduced. CONCLUSIONS: The cytotoxic properties of the produced fungal enzyme indicated significant growth inhibition in cancer cells while having a little toxic effect on normal cells. The possibility of mass production alongside having suitable cytotoxic and kinetic properties suggest the probable use of the produced l-asparaginase for further researches as a potential chemotherapeutic agent. SIGNIFICANCE AND IMPACT OF THE STUDY: The lack of significant l-glutaminase activity and promising toxicity properties in S. strictum and the closer evolutionary relativeness of fungi enzymes to human enzymes compared to bacterial enzymes suggest a new source with lower toxicity and anti-cancerous properties, causing less side effect problems.


Assuntos
Antineoplásicos/farmacologia , Asparaginase/farmacologia , Hypocreales/metabolismo , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Asparaginase/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células HL-60 , Humanos , Hypocreales/enzimologia , Células K562 , Cinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
6.
World J Microbiol Biotechnol ; 36(2): 31, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048066

RESUMO

Biogenic production of nanoparticles is eco-friendly, less expensive method with various medical and biological applications. Nanotechnology along with photodynamic therapy is gaining tremendous importance with enhanced efficacy. The present work was aimed to evaluate methanolic extracts and nanoparticles of two selected plants (Datura suavolens and Verbina tenuisecta) for cytotoxic photodynamic, antioxidant and antimicrobial study. Both extract and silver (5 mM) nanoparticles of Datura plant showed significant activities against bacterial strains. Maximum ZOI of 27.3 ± 1.6 mm was observed with nanoparticles of Datura branches with minimum inhibitory (MIC) value of 32 µg/ml. In case of antifungal and antioxidant assay samples were moderately active. Silver nanoparticles and extracts were effective against rhabdomyosarcoma cell line with lowest IC50 value of 42.5 ± 0.6 µg/ml and percent viability of 25.6 ± 1.3 of Verbena tenuisecta. However, nanoparticles of Datura leaves and branches were more potent with IC50 value of 2.4 ± 0.9 µg/ml and 7.8 ± 1.1 µg/ml respectively. The result of photodynamic study showed that efficacy of photosensitizer was enhanced and percent viability reduced when nanoparticles used as an adjunct. The color change and UV spectra (415‒425 nm) indicated the production of nanoparticles. Fourier transform infrared spectroscopy (FTIR) spectra showed presence of different functional groups e.g., hydroxyl, carbonyl and amino. Nanoparticles are sphenoid in morphology and size ranges between 20-150 nm. Current study showed these silver nanoparticles can be used as cytotoxic agent in photodynamic therapy and can play a critical role to establish medicinal potential of selected plants.


Assuntos
Datura/química , Metanol/farmacologia , Prata/farmacologia , Verbena/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nanopartículas Metálicas , Metanol/química , Metanol/isolamento & purificação , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/isolamento & purificação , Fármacos Fotossensibilizantes/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Prata/química , Prata/isolamento & purificação
7.
Alkaloids Chem Biol ; 83: 1-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32098648

RESUMO

Lamellarins are marine alkaloids containing fused 14-phenyl-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinoline or non-fused 3,4-diarylpyrrole-2-carboxylate ring systems. To date, more than 50 lamellarins have been isolated from a variety of marine organisms, such as mollusks, tunicates, and sponges. Many of them, especially fused type I lamellarins, exhibit impressive biological activity, such as potent cytotoxicity, topoisomerase I inhibition, protein kinases inhibition, and anti-HIV-1 activity. Due to their useful biological activity and limited availability from natural sources, a number of synthetic methods have been developed. In this chapter, we present an updated and comprehensive review on lamellarin alkaloids summarizing their isolation, synthesis, and biological activity.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Fármacos Anti-HIV/farmacologia , Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirróis/isolamento & purificação , Pirróis/farmacologia , Inibidores da Topoisomerase I/farmacologia , Alcaloides/síntese química , Alcaloides/química , Animais , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Humanos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/isolamento & purificação , Pirróis/síntese química , Pirróis/química , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/isolamento & purificação
9.
Curr Pharm Biotechnol ; 21(11): 1070-1078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101118

RESUMO

INTRODUCTION: The plant, Astilboides tabularis (Hemsl.) Engler, is used in Chinese and Korean medicine to regulate blood sugar levels; however, little is known about its precise effects. MATERIALS AND METHODS: In this study, we aimed to measure the composition as well as the antioxidant, and anti-proliferative capacities of A. tabularis. Various extracts were generated using different organic solvents, and in vitro antioxidant activities were evaluated using DPPH free radical-scavenging and reducing power assays. The extracts were also evaluated based on their ability to inhibit lipopolysaccharide (LPS)-induced Nitric Oxide (NO) production in RAW 264.7 cells. RESULTS: Research shows that the A. tabularis ethyl acetate (EtOAc) extract showed significant antioxidant activity. Additionally, this extract could inhibit the LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines in RAW 264.7 cells, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-1 beta (IL-1ß). Notably, the A. tabularis EtOAc extract also displayed potent cytotoxic effects against MCF-7 and HeLa cancer cell lines, as determined by MTT assays. Lastly, total phenol and flavonoid content was measured for all extracts, and four flavonoid compounds-catechin, kaempferol, quercitrin, and isoquercetin were isolated from the EtOAc extract. Their structures were confirmed using mass spectrometry and nuclear magnetic resonance, and these isolated compounds were found to display potent DPPH free radical-scavenging activity. CONCLUSION: Thus, our data suggest that phenolic compounds in A. tabularis extracts promote antioxidant activity, and furthermore, these extracts show numerous features that indicate potential for therapeutic development.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Saxifragaceae/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/química , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres/química , Células HeLa , Humanos , Lipopolissacarídeos/farmacologia , Células MCF-7 , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polifenóis/química , Polifenóis/isolamento & purificação , Células RAW 264.7
10.
Org Biomol Chem ; 18(4): 642-645, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31916553

RESUMO

Photeroids A (1) and B (2), two structurally fascinating meroterpenoids, were isolated from the deep-sea-derived fungus Phomopsis tersa FS441. Their structures were sufficiently established by a comprehensive interpretation of the spectroscopic data, NMR spectra, and ECD calculation. Photeroids A and B represented the first phenolic sesquiterpene meroterpenoids featuring a highly fused 6/6/6/6 tetracyclic ring system derived through a rarely-occurring hetero-Diels-Alder reaction via an orthoquinone methide intermediate. Additionally, they were also evaluated for their cytotoxic activities against four human cancer cells, wherein compounds 1 and 2 exhibited moderate cytotoxic activities.


Assuntos
Ascomicetos/química , Fenóis/farmacologia , Sesquiterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Fenóis/química , Fenóis/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação
11.
PLoS One ; 15(1): e0226979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31952077

RESUMO

Libidibia ferrea (juca) is a plant belonging to the Fabaceae (Leguminosae) family, whose antioxidant activity has been widely described in the literature. We evaluated this parameter of Aqueous ethanol extract (AE), ethyl acetate (ACO), chloroform (CLO) and hexane (HEX) extracts of L. ferrea. We then tested the most active extract for its toxicity and ability to inhibit migratory activity in the ACP02 gastric adenocarcinoma cell line in vitro. The AE and ACO extracts both had antioxidant activity, the AE extract showing greater potential. This may reflect that both extracts contained phenolic compounds. Although AE extract showed no cytotoxic, mutagenic or genotoxic effect, it altered cell morphology and migration activity. Analysis of apoptosis/necrosis indicated that this parameter does not appear to account for the apparent ability of AE to inhibit cancer cell migration. We speculate that the morphological changes in AE-treated cells could be due to cytoskeleton alterations related to the presence of myo-inositol in AE extract. Together, our results demonstrate this extract of L. ferrea can act as an exogenous antioxidant and might prove useful in efforts to fight secondary tumors.


Assuntos
Antineoplásicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Caesalpinia/química , Movimento Celular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Etanol , Humanos , Solventes/química , Neoplasias Gástricas/patologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-31918307

RESUMO

The aim of this work is to develop an efficient and economical method for the enrichment of total flavonoids from Pteris ensiformis Burm. extracts. Resin screening, adsorption kinetics, adsorption isotherms and thermodynamics were successively researched prior to the dynamic adsorption and desorption tests. NKA-II resin was chosen as the best adsorbent, and the adsorption data were best described by the pseudo-second-order kinetics model and Langmuir isotherm model. The optimum enrichment conditions were as follows: for adsorption the total flavonoids concentration, flow rate and volume of sample were 1.84 mg/mL, 2 BV/h and 5 BV, respectively, and for desorption the flavonoids-loaded NKA-II resin column was desorbed by 7 BV of 50% ethanol at a rate of 2 BV/h. The product had a 6.63-fold higher total flavonoids content than crude extracts, and the recovery yield of total flavonoids was 80.65%. Furthermore, flavonoids-enriched extracts exhibited higher in vitro scavenging activity against superoxide anion radical and hydroxyl radical than crude extracts. In addition, higher antiproliferative activity of flavonoids-enriched extracts against MCF-7 and HepG-2 cell lines was also found as compared to the crude extracts. The developed method is appropriate for large-scale enrichment of total flavonoids from Pteris ensiformis Burm. extracts in the food and pharmaceutical industries.


Assuntos
Antioxidantes , Proliferação de Células/efeitos dos fármacos , Flavonoides , Pteris/química , Adsorção , Antineoplásicos/análise , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/análise , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/análise , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Células Hep G2 , Humanos , Células MCF-7 , Extratos Vegetais/química , Resinas Sintéticas/química
13.
Chem Biodivers ; 17(1): e1900547, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31916685

RESUMO

Four previously unreported chromones, 5-hydroxy-2-(hydroxymethyl)-8-methoxy-4H-chromen-4-one (1), (5R,7S)-5,7-dihydroxy-2-propyl-5,6,7,8-tetrahydro-4H-chromen-4-one (2), (5R,7S)-5,7-dihydroxy-2-methyl-5,6,7,8-tetrahydro-4H-chromen-4-one (3), and (5R,7S)-5,7-dihydroxy-2-[(E)-prop-1-en-1-yl]-5,6,7,8-tetrahydro-4H-chromen-4-one (4), as well as one known analogue 5-hydroxy-2-methyl-4H-chromen-4-one (5) were isolated from the fermentation broth of the endophytic fungus Colletotrichum gloeosporioides derived from the mangrove Ceriops tagal. Their structures were elucidated based on extensive spectroscopic analyses. The absolute configurations of 2-4 were determined by comparison the experimental and calculated electronic circular dichroism (ECD) spectra. Compound 2 showed cytotoxic activity against A549 cell line with the IC50 value of 0.094 mm.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Cromonas/isolamento & purificação , Cromonas/farmacologia , Colletotrichum/química , Células A549 , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Cromonas/química , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
14.
Chemosphere ; 243: 125456, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995895

RESUMO

In this paper degradation of cytarabine drug has been studied through electrochemical oxidation process by using graphite electrode. The performance of graphite electrode on the degradation of cytarabine was evaluated by investigating the effects of key parameters: pH (3-9), current density (5-20 mA cm-2) and initial pollutant concentration (5-50 mg L-1) with 0.05 M NaCl as supporting electrolyte. Highest removal efficiency (98%) for 20 mg L-1 of initial cytarabine solution was attained within 60 min electrolysis at 10 mA cm-2. The increase in degradation rate of cytarabine was possibly because of the active chlorine species originated at anode during the electrolysis. Further, efficiency of the graphite electrodes was compared with a metal electrode (copper) and results showed that the cytarabine degradation was facilitated by the in-situ generated OH radicals. However, only 82% of cytarabine was removed after 60 min of reaction time at 15 mA cm-2. The scum of Cu2+ ions deposited on the anode surface inhibit the mass transfer among the cytarabine molecules and generated hydroxyl radicals. The kinetic study also suggests faster reaction rate at graphite (0.12 min-1) than copper (0.05 min-1) electrode. The increase in electrolyte concentration enhanced the degradation rate and decreased the energy consumption from 3.66 to 0.66 kWh m-3. Cytosine was identified as the major transformation product from the UV-Vis spectral analysis and LC-MS analysis. Further, total organic carbon analysis depicts that only 60% of the parent molecule was mineralized. Hence, graphite was found to be an efficient anode material as compared to copper for cytarabine degradation.


Assuntos
Citarabina/isolamento & purificação , Eletrólise/métodos , Grafite/química , Poluentes Químicos da Água/isolamento & purificação , Antineoplásicos/isolamento & purificação , Cloro , Eletrodos , Cinética , Oxirredução , Poluentes Químicos da Água/química
15.
Phytother Res ; 34(4): 685-720, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31908068

RESUMO

Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T-cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.


Assuntos
Anti-Inflamatórios , Antineoplásicos , Ácido Elágico/farmacologia , Romã (Fruta)/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Células Cultivadas , Estudos Clínicos como Assunto/métodos , Estudos Clínicos como Assunto/estatística & dados numéricos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Ácido Elágico/isolamento & purificação , Ácido Elágico/uso terapêutico , Frutas/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
16.
Sci Rep ; 10(1): 1442, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996737

RESUMO

Discovering anticancer drugs that do not have adverse side effects has been a developing research field worldwide in recent decades. In this work, four previously undescribed cytotoxic diterpenoids were isolated from the aerial parts of Isodon excisoides. Interestingly, these four diterpenoids were two pairs of tautomers that were first reported in plants. Their structures were further elucidated using various spectroscopic methods. The tautomerization phenomenon and mechanism for these two pairs of tautomers were emphatically described. The theoretical simulation results indicated that the diterpene tautomerization is greatly related to certain factors, including the existence of a transition state, the change of bond length and the level of conversion energy; the tautomerization for the two pairs of tautomers is mainly caused by proton transfer. For bioassays, the cytotoxicities of the tautomers against five human cancer cell lines were also investigated. The results indicated that each of the four diterpenoids showed significant cytotoxicity in at least three cell lines and could serve as potential anticancer agents for further investigation.


Assuntos
Antineoplásicos/química , Neoplasias do Colo/tratamento farmacológico , Alcaloides Diterpenos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose , Alcaloides Diterpenos/isolamento & purificação , Alcaloides Diterpenos/farmacologia , Descoberta de Drogas , Células HCT116 , Humanos , Isodon , Estrutura Molecular , Análise Espectral
17.
Mar Drugs ; 18(1)2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940767

RESUMO

Marine algae represent a prolific source of filamentous fungi for bioprospecting. In continuation of our search for new anticancer leads from fungi derived from the brown alga Fucus vesiculosus, an endophytic Pyrenochaetopsis sp. FVE-001 was selected for an in-depth chemical analysis. The crude fungal extract inhibited several cancer cell lines in vitro, and the highest anticancer activity was tracked to its CHCl3-soluble portion. A bioactivity-based molecular networking approach was applied to C18-SPE fractions of the CHCl3 subextract to predict the bioactivity scores of metabolites in the fractions and to aid targeted purification of anticancer metabolites. This approach led to a rapid isolation of three new decalinoylspirotetramic acid derivatives, pyrenosetins A-C (1-3) and the known decalin tetramic acid phomasetin (4). The structures of the compounds were elucidated by extensive NMR, HR-ESIMS, FT-IR spectroscopy, [α]D and Mosher's ester method. Compounds 1 and 2 showed high anticancer activity against malignant melanoma cell line A-375 (IC50 values 2.8 and 6.3 µM, respectively), in line with the bioactivity predictions. This is the first study focusing on secondary metabolites of a marine-derived Pyrenochaetopsis sp. and the second investigation performed on the member of the genus Pyrenochaetopsis.


Assuntos
Antineoplásicos/farmacologia , Ascomicetos/química , Bioensaio/métodos , Descoberta de Drogas/métodos , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fucus/microbiologia , Humanos , Concentração Inibidora 50
18.
Molecules ; 25(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936488

RESUMO

Activin-like kinase 5 (ALK-5) is involved in the physiopathology of several conditions, such as pancreatic carcinoma, cervical cancer and liver hepatoma. Cellular events that are landmarks of tumorigenesis, such as loss of cell polarity and acquisition of motile properties and mesenchymal phenotype, are associated to deregulated ALK-5 signaling. ALK-5 inhibitors, such as SB505154, GW6604, SD208, and LY2157299, have recently been reported to inhibit ALK-5 autophosphorylation and induce the transcription of matrix genes. Due to their ability to impair cell migration, invasion and metastasis, ALK-5 inhibitors have been explored as worthwhile hits as anticancer agents. This work reports the development of a structure-based virtual screening (SBVS) protocol aimed to prospect promising hits for further studies as novel ALK-5 inhibitors. From a lead-like subset of purchasable compounds, five molecules were identified as putative ALK-5 inhibitors. In addition, molecular dynamics and binding free energy calculations combined with pharmacokinetics and toxicity profiling demonstrated the suitability of these compounds to be further investigated as novel ALK-5 inhibitors.


Assuntos
Antineoplásicos/química , Conformação Proteica/efeitos dos fármacos , Inibidores de Proteínas Quinases/química , Receptor do Fator de Crescimento Transformador beta Tipo I/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Sítios de Ligação , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica/efeitos dos fármacos , Inibidores de Proteínas Quinases/isolamento & purificação , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/química , Quinolinas/química , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/ultraestrutura , Interface Usuário-Computador
19.
Prep Biochem Biotechnol ; 50(3): 260-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31762381

RESUMO

Anti-leukemic enzyme L-asparaginase despite having significant applicability in medicine, holds side effects attributed to glutaminase activity and endotoxin content. Glutaminase activity proves to be toxic to non-tumor cells as glutamine is an essential amino acid. Endotoxin illicit the production of vasoactive amines and induce septic shock. Hence there is a need for glutaminase free L-asparaginase with minimum endotoxin level. The report aims at the development of a downstream process for purification of glutaminase free L-asparaginase and subsequent endotoxin removal. Producing bacteria were isolated from various soil samples and screened initially for asparaginase and glutaminase activity. The glutaminase free L-asparaginase producing bacteria were identified as Bacillus altitudinis. Production of L-asparaginase was optimized. The optimum medium comprised of comprising Lactose (1.5 g/L), NaCl (1.2 g/L), Yeast extract (5 g/L), L-asparagine (20 g/L) with pH 7.0 and incubation time of 18 h. Kinetic parameters Km and Vmax were computed to be 9.09x10-2M and 0.09 M/S. L-asparaginase Purification was achieved with a specific activity of 800 U/mg of enzyme. Molecular weight of the purified L-asparaginase was determined to be around 35 KDa using SDS-PAGE. The developed process also brought down the endotoxin content below the FDA recommended level. The endotoxin content of the purified enzyme was determined to be 0.015EU/mL.


Assuntos
Antineoplásicos , Asparaginase , Bacillus/enzimologia , Endotoxinas/análise , Microbiologia do Solo , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Asparaginase/química , Asparaginase/isolamento & purificação
20.
Chem Biodivers ; 17(1): e1900560, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31769919

RESUMO

Borrelidins M-O (1-3), along with four previously known family members (4-7), were isolated from marine pulmonated mollusks Onchidium sp. associated Streptomyces olivaceus SCSIO LO13. The structures of 1-3 were elucidated by extensive spectral analyses of HR-ESI-MS, 1D and 2D NMR data. In addition, the cytotoxic and antibacterial activities of 1-7 were evaluated enabling us to propose some tentative structure-activity relationships (SARs), especially those involving modifications at C(22) and the moieties at C(7) and C(8) of the borrelidin scaffold.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Streptomyces/química , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA