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1.
Sci Rep ; 14(1): 10484, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714767

RESUMO

The current research aimed to study the green synthesis of silver oxide nanoparticles (AgONPs) using Rhynchosia capitata (RC) aqueous extract as a potent reducing and stabilizing agent. The obtained RC-AgONPs were characterized using UV, FT-IR, XRD, DLS, SEM, and EDX to investigate the morphology, size, and elemental composition. The size of the RC-AgONPs was found to be ~ 21.66 nm and an almost uniform distribution was executed by XRD analysis. In vitro studies were performed to reveal biological potential. The AgONPs exhibited efficient DPPH free radical scavenging potential (71.3%), reducing power (63.8 ± 1.77%), and total antioxidant capacity (88.5 ± 4.8%) to estimate their antioxidative power. Antibacterial and antifungal potentials were evaluated using the disc diffusion method against various bacterial and fungal strains, and the zones of inhibition (ZOI) were determined. A brine shrimp cytotoxicity assay was conducted to measure the cytotoxicity potential (LC50: 2.26 µg/mL). In addition, biocompatibility tests were performed to evaluate the biocompatible nature of RC-AgONPs using red blood cells, HEK, and VERO cell lines (< 200 µg/mL). An alpha-amylase inhibition assay was carried out with 67.6% inhibition. Moreover, In vitro, anticancer activity was performed against Hep-2 liver cancer cell lines, and an LC50 value of 45.94 µg/mL was achieved. Overall, the present study has demonstrated that the utilization of R. capitata extract for the biosynthesis of AgONPs offers a cost-effective, eco-friendly, and forthright alternative to traditional approaches for silver nanoparticle synthesis. The RC-AgONPs obtained exhibited significant bioactive properties, positioning them as promising candidates for diverse applications in the spheres of medicine and beyond.


Assuntos
Nanopartículas Metálicas , Compostos de Prata , Nanopartículas Metálicas/química , Animais , Humanos , Compostos de Prata/química , Compostos de Prata/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Artemia/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Química Verde/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Células Vero , Antifúngicos/farmacologia , Antifúngicos/química , Prata/química , Prata/farmacologia , Óxidos
2.
Chemosphere ; 357: 142092, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653396

RESUMO

Climate change further the world's human population increase is a mainstream political issue, and it's critical to search for solutions to produce enough food to feed everyone. Pesticides and fertilizers have been used as an easy solution to prevent pests and increase food production. Nevertheless, their overuse has dangerous effects on the ecosystems and communities. Oxyfluorfen (Oxy) and copper (Cu) based formulations are used as pesticides and widely applied on agricultural fields for crop protection. However, they have shown negative effects on non-target species. So, this work proposes to: a)determine the lethal concentration of Oxy and Cu to the zooplankton, Artemia franciscana, at different temperatures (15 °C, 20 °C and 25 °C); b)understand the biochemical impacts of these chemicals at the different temperatures scenarios, on A. franciscana and c)evaluate the impact of the climate changes, particularly the temperature increase, on this species sensitivity to the tested pesticides. Acute and sub-lethal bioassays with Oxy and Cu were performed at different temperatures to determine the lethal concentration of each chemical and to understand the effects of the compounds at different temperatures on the biochemical profiles of A. franciscana. Results showed an increase in chemicals toxicity with the temperature, and Oxy was revealed to be more noxious to A. franciscana than Cu; at a biochemical level, significant differences were observed among temperatures, with the biggest differences between the organisms exposed to 15 °C and 25 °C. Overall, a decrease in fatty acids (FA) and sugars was observed with the increase in Cu and oxyfluorfen concentrations. Different trends were observed with temperature increase, with FA increase in the organisms exposed to Cu and the opposite was observed in the ones exposed to oxyfluorfen. Sugar content decreases in the organisms exposed to oxyfluorfen with temperature increase and showed a non-linear behaviour in the ones exposed to Control and Cu treatments.


Assuntos
Artemia , Cobre , Éteres Difenil Halogenados , Praguicidas , Temperatura , Animais , Cobre/toxicidade , Éteres Difenil Halogenados/toxicidade , Artemia/efeitos dos fármacos , Praguicidas/toxicidade , Praguicidas/análise , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Mudança Climática
3.
Microsc Res Tech ; 87(7): 1479-1493, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38407375

RESUMO

For many years, the synthesis of graphene oxide (GO) had involved exfoliating graphite flakes, and the methods applied were expensive and time-consuming. Thus, an attempt had been made to create an inventive, less expensive method for the synthesis of GO using unrefined, raw carbon-containing material. Modified Hummer's method was used to prepare GO from banana peel. In addition, the metallic silver nanocomposite was also synthesized along with laoding of drug Rocephin where they interact with each other through electrostatic hydrogen bond interaction. The degree of crystallinity and the crystallite size were through x-ray diffraction (XRD) analysis and the crystallite size of AgNPs was found to be 40.40 nm. The scanning electron microscopy (SEM) analysis shows that the morphology of the GO gradually changes with the addition of AgNPs and Rocephin. A blue shift was seen in the absorbance maxima of the raw carbon upon the conjugation of Rocephin in UV analysis. The Fourier-transform infrared spectroscopy, and energy dispersive X-ray (EDX) spectroscopy were used to determine the chemical composition of the samples. Furthermore, a broad biological screening of the synthesized samples had been carried out following the total reducing power (TRP), total antioxidant capacity (TAC), antibacterial, antifungal, MTT (Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells) cell viability, brine shrimp lethality, and hemolytic protocols. Significant results were obtained, and the Rocephin-GO-AgNPs had depicted promising activity as compared with their counterparts. RESEARCH HIGHLIGHTS: The GO was prepared from the raw carbon extracted from banana peels and was used as a substrate for the synthesis Graphene oxide silver nanoparticles (GO-AgNPs) and Rocephin-loaded graphene oxide silver nanoparticles (Rocephin-GO-AgNPs) The structural and compositional analysis of the nanomaterial was carried out, and they were screened for several biomedical applications. The Rocephin-GO-AgNPs exhibit the highest activity as compared with their counterparts.


Assuntos
Grafite , Nanopartículas Metálicas , Nanocompostos , Prata , Grafite/química , Prata/química , Prata/farmacologia , Nanocompostos/química , Animais , Nanopartículas Metálicas/química , Humanos , Artemia/efeitos dos fármacos , Difração de Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Antioxidantes/farmacologia , Antioxidantes/química , Antibacterianos/farmacologia , Microscopia Eletrônica de Varredura , Musa/química , Anti-Infecciosos/farmacologia
4.
Mar Drugs ; 20(2)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35200611

RESUMO

Palytoxin (PLTX) is a highly toxic polyether identified in various marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. In addition to adverse effects in humans, negative impacts on different marine organisms have been often described during Ostreopsis blooms and the concomitant presence of PLTX and its analogues. Considering the increasing frequency of Ostreopsis blooms due to global warming, PLTX was investigated for its effects on Artemia franciscana, a crustacean commonly used as a model organism for ecotoxicological studies. At concentrations comparable to those detected in culture media of O. cf. ovata (1.0-10.0 nM), PLTX significantly reduced cysts hatching and induced significant mortality of the organisms, both at larval and adult stages. Adults appeared to be the most sensitive developmental stage to PLTX: significant mortality was recorded after only 12 h of exposure to PLTX concentrations > 1.0 nM, with a 50% lethal concentration (LC50) of 2.3 nM (95% confidence interval = 1.2-4.7 nM). The toxic effects of PLTX toward A. franciscana adults seem to involve oxidative stress induction. Indeed, the toxin significantly increased ROS levels and altered the activity of the major antioxidant enzymes, in particular catalase and peroxidase, and marginally glutathione-S-transferase and superoxide dismutase. On the whole, these results indicate that environmentally relevant concentrations of PLTX could have a negative effect on Artemia franciscana population, suggesting its potential ecotoxicological impact at the marine level.


Assuntos
Acrilamidas/toxicidade , Artemia/efeitos dos fármacos , Venenos de Cnidários/toxicidade , Toxinas Marinhas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Acrilamidas/administração & dosagem , Animais , Venenos de Cnidários/administração & dosagem , Relação Dose-Resposta a Droga , Ecotoxicologia , Dose Letal Mediana , Estágios do Ciclo de Vida , Toxinas Marinhas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
5.
Molecules ; 27(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35056790

RESUMO

The present study was designed to evaluate polarity-dependent extraction efficiency and pharmacological profiling of Polygonum glabrum Willd. Crude extracts of leaves, roots, stems, and seeds, prepared from solvents of varying polarities, were subjected to phytochemical, antioxidant, antibacterial, antifungal, antidiabetic, and cytotoxicity assays. Maximum extraction yield (20.0% w/w) was observed in the case of an acetone:methanol (AC:M) root extract. Distilled water:methanol (W:M) leaves extract showed maximum phenolic contents. Maximum flavonoid content and free radical scavenging potential were found in methanolic (M) seed extract. HPLC-DAD quantification displayed the manifestation of substantial quantities of quercetin, rutin, gallic acid, quercetin, catechin, and kaempferol in various extracts. The highest ascorbic acid equivalent total antioxidant capacity and reducing power potential was found in distilled water roots and W:M leaf extracts, respectively. Chloroform (C) seeds extract produced a maximum zone of inhibition against Salmonella typhimurium. Promising protein kinase inhibition and antifungal activity against Mucor sp. were demonstrated by C leaf extract. AC:M leaves extract exhibited significant cytotoxic capability against brine shrimp larvae and α-amylase inhibition. Present results suggest that the nature of pharmacological responses depends upon the polarity of extraction solvents and parts of the plant used. P. glabrum can be considered as a potential candidate for the isolation of bioactive compounds with profound therapeutic importance.


Assuntos
Fracionamento Químico/métodos , Cromatografia Líquida de Alta Pressão/métodos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Polygonum/química , Animais , Anti-Infecciosos/análise , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/farmacologia , Artemia/efeitos dos fármacos , Ensaios Enzimáticos , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/análise , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/análise , Polifenóis/química , Polifenóis/farmacologia , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia
6.
Chem Biol Interact ; 351: 109714, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34710376

RESUMO

The use of schiff base complex against microbial agentes a has recently received more attention as a strategy to combat infections caused by multidrug-resistant bacteria and leishmania. This study aimed to evaluate the toxicity, antibacterial and leishmanicidal activities of the nickel (II) chloride schiff base complex ([Ni(L2)] against Leishmania amazonensis promastigote, multi-resistant bacterial strains and evaluate to modulate antibiotic activity against multi-resistant bacterial. The schiff base complex was characterized by the techniques of elemental analysis, Fourier transform infrared spectroscopy (FTIR), UV-vis absorption spectroscopy and thermal analysis (TGA/DTG/DSC). The [Ni(L2)] complex presented moderate toxicity in saline artemia (LC50 = 150.8 µg/mL). In leishmanicidal assay, the NiL2 complex showed values of IC50 of (6.079 µg/mL ± 0.05656 at the 24 h), (0.854 µg/mL ± 0.02474, 48 h) and (1.076 µg/mL ± 0.04039, 72 h). In antibacterial assay, the [Ni(L2)] complex presented significant inhibited the bacterial growth of P. aeruginosa (MIC = 256 µg/mL). However, [Ni(L2)] complex did not present clinically relevant minimum inhibitory concentration (MIC ≥1024 µg/mL) against S. aureus and E. coli. The combination of [Ni(L2)] complex and antibacterial drugs resulted in the increased antibiotic activity of gentamicin and amikacin against S. aureus and E.coli multi-resistant strains. Thus, our results showed that [Ni(L2)] complex is a promising molecule for the development of new therapies associated with aminoglycoside antibiotics and in disease control related to resistant bacteria and leishmaniasis.


Assuntos
Antibacterianos/farmacologia , Complexos de Coordenação/farmacologia , Bases de Schiff/farmacologia , Tripanossomicidas/farmacologia , Amicacina/farmacologia , Animais , Antibacterianos/química , Artemia/efeitos dos fármacos , Complexos de Coordenação/química , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Gentamicinas/farmacologia , Leishmania infantum/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Níquel/química , Testes de Sensibilidade Parasitária , Pseudomonas aeruginosa/efeitos dos fármacos , Bases de Schiff/química , Staphylococcus aureus/efeitos dos fármacos , Tripanossomicidas/química
7.
Dalton Trans ; 51(1): 185-196, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34877947

RESUMO

In this paper, Cu(II), Mn(II) and Zn(II) complexes with N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL1Cl) were synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis and DFT calculations. In all three complexes, a ligand (L1) is coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Cu(II) and Zn(II) form mononuclear penta-coordinated complexes [CuL1(N3)(CH3OH)]BF4 and [ZnL1(N3)2], respectively, while Mn(II) forms a binuclear [Mn2L12(µ-1,1-N3)2(N3)2]·2CH3OH complex, with unusual distorted trigonal-prismatic geometry around the metal centers. The antimicrobial activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two yeasts and one fungal strain. The binuclear Mn(II) complex showed antifungal activity of similar intensity to amphotericin B. Based on the results of the brine shrimp test and DPPH radical scavenging activity, the most active Cu(II) and Mn(II) complexes were selected for evaluation of cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and one normal cell line HaCaT. Both complexes showed significant activity. It should be pointed out that the activity of the Mn(II) complex against the MCF7 breast cancer cell line is only slightly weaker than that of cisplatin, but with selectivity to the tumor cell line in comparison to normal HaCaT cells, which is non-existent in the case of cisplatin.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Complexos de Coordenação/farmacologia , Teoria da Densidade Funcional , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Artemia/efeitos dos fármacos , Compostos de Bifenilo/antagonistas & inibidores , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Cobre/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Hidrazonas/química , Hidrazonas/farmacologia , Manganês/química , Manganês/farmacologia , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Picratos/antagonistas & inibidores , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Zinco/química , Zinco/farmacologia
8.
Molecules ; 26(23)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34885940

RESUMO

Peperomia Ruiz and Pav, the second largest genus of the Piperaceae, has over the years shown potential biological activities. In this sense, the present work aimed to carry out a seasonal and circadian study on the chemical composition of Peperomia circinata essential oils and aromas, as well as to evaluate the preliminary toxicity in Artemia salina Leach and carry out an in silico study on the interaction mechanism. The chemical composition was characterized by gas chromatography (GC/MS and GC-FID). In the seasonal study the essential oil yields had a variation of 1.2-7.9%, and in the circadian study the variation was 1.5-5.6%. The major compounds in the seasonal study were ß-phellandrene and elemicin, in the circadian they were ß-phellandrene and myrcene, and the aroma was characterized by the presence of ß-phellandrene. The multivariate analysis showed that the period and time of collection influenced the essential oil and aroma chemical composition. The highest toxicity value was observed for the essential oil obtained from the dry material, collected in July with a value of 14.45 ± 0.25 µg·mL-1, the in silico study showed that the major compounds may be related to potential biological activity demonstrated by the present study.


Assuntos
Artemia/efeitos dos fármacos , Óleos Voláteis/análise , Óleos Voláteis/toxicidade , Peperomia/química , Monoterpenos Acíclicos/análise , Monoterpenos Acíclicos/toxicidade , Alcenos/análise , Alcenos/toxicidade , Animais , Monoterpenos Cicloexânicos/análise , Monoterpenos Cicloexânicos/toxicidade , Pirogalol/análogos & derivados , Pirogalol/análise , Pirogalol/toxicidade , Estações do Ano
9.
Molecules ; 26(24)2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34946755

RESUMO

Annona muricata (Am) is a plant used in traditional Mexican medicine to treat cancer. In this study, ethanol extracts of Am collected in Acapulco and Tecpan from Guerrero state were evaluated orally on Balb/c mice inoculated with 4T1 cells, for cytotoxic activity (CA) on 4T1 cells, in brine shrimp lethality assay (BSLA), and for acute oral toxicity in mice. In addition, ethanol extracts were subjected to high-performance liquid chromatography (HPLC) with diode array detection. Results showed that the extracts collected in December in Acapulco (AcDe) and Tecpan (TeDe) exhibited the most significant antitumor and cytotoxic activity. In the BSLA, the most important effect was observed in the extracts from Acapulco and Tecpan collected in June (AcJu) and August (TeAg), respectively. The samples from Acapulco (AcJu, and AcAg) and Tecpan (TeJu and TeAg) showed the highest toxicity. The analysis of the extracts, AcDe and TeDe, by HPLC revealed that flavonoids, rutin, narcissin, and nicotinflorin were the major components. These findings suggest that extracts from Am collected in Acapulco and Tecpan in the month of December may be an important source to obtain flavonoid glycosides with anticancer potential specifically against breast cancer. This also supports the use of Am to treat cancer in Mexican traditional medicine.


Assuntos
Annona/química , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Artemia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Medicina Tradicional , México , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células Tumorais Cultivadas
10.
Int J Mol Sci ; 22(20)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34681952

RESUMO

A nano-revolution based on the green synthesis of nanomaterials could affect all areas of human life, and nanotechnology represents a propitious platform for various biomedical applications. During the synthesis of nanoparticles, various factors can control their physiognomies and clinical activities. Light is one of the major physical factors that can play an important role in tuning/refining the properties of nanoparticles. In this study, biocompatible monometallic (AgNPs and ZnONPs) and bimetallic Ag-ZnONPs (0.1/0.1 and 0.1/0.5) were synthesized under UV-C light irradiation from the leaf extract of Morus macroura, which possesses enriched TPC (4.238 ± 0.26 mg GAE/g DW) and TFC (1.073 ± 0.18 mg QE/g DW), as well as strong FRSA (82.39%). These green synthesized NPs were evaluated for their anti-diabetic, anti-glycation, and biocompatibility activities. Furthermore, their anti-cancerous activity against HepG2 cell lines was assessed in terms of cell viability, production of reactive oxygen/nitrogen species, mitochondrial membrane potential, and apoptotic caspase-3/7 expression and activity. Synthesized NPs were characterized by techniques including ultraviolet-visible spectroscopy, SEM, EDX, FTIR, and XRD. UV-C mediated monometallic and bimetallic NPs showed well-defined characteristic shapes with a more disperse particle distribution, definite crystalline structures, and reduced sizes as compared to their respective controls. In the case of clinical activities, the highest anti-diabetic activity (67.77 ± 3.29% against α-amylase and 35.83 ± 2.40% against α-glucosidase) and anti-glycation activity (37.68 ± 3.34% against pentosidine-like AGEs and 67.87 ± 2.99% against vesperlysine-like AGEs) was shown by UV-C mediated AgNPs. The highest biocompatibility (IC50 = 14.23 ± 1.68 µg/mL against brine shrimp and 2.48 ± 0.32% hemolysis of human red blood cells) was shown by UV-C mediated ZnONPs. In the case of anti-cancerous activities, the lowest viability (23.45 ± 1.40%) with enhanced ROS/NOS production led to a significant disruption of mitochondrial membrane potential and greater caspase-3/7 gene expression and activity by UV-C mediated bimetallic Ag-ZnONPs (0.1/0.5). The present work highlights the positive effects of UV-C light on physico-chemical physiognomies as well as the clinical activities of NPs.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas Metálicas/administração & dosagem , Morus/química , Extratos Vegetais/farmacologia , Prata/química , Óxido de Zinco/química , Animais , Apoptose , Artemia/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Glicólise , Hemólise/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Fisiognomia , Raios Ultravioleta , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/química
11.
Mar Drugs ; 19(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34677447

RESUMO

Three new cyanobactins, trikoramides B (1)-D (3), have been isolated from the marine cyanobacterium, Symploca hydnoides, following a preliminary bioassay-guided isolation of the two most active polar fractions based on the brine shrimp toxicity assay. These new cyanobactins are new analogues of the previously reported cytotoxic trikoramide A (4) with differences mainly in the C-prenylated cyclotryptophan unit. Their planar structures were elucidated from their 1D and 2D NMR spectral data in combination with the HRMS/MS data. Marfey's method, 2D NOESY NMR spectroscopic and ECD spectra analyses were used to determine the absolute stereochemistry of trikoramides B (1)-D (3). Trikoramides B (1) and D (3) exhibited cytotoxicity against MOLT-4 acute lymphoblastic leukemia cell line with IC50 values of 5.2 µM and 4.7 µM, respectively. Compounds 1 and 3 were also evaluated for their quorum-sensing inhibitory assay based on the Pseudomonas aeruginosa PAO1 lasB-gfp and rhlA-gfp bioreporter strains. Although trikoramide B (1) exhibited weak quorum-sensing inhibitory activity, the Br-containing trikoramide D (3) exhibited moderate to significant dose-dependent quorum-sensing inhibitory activities against PAO1 lasB-gpf and rhlA-gfp bioreporter strains with IC50 values of 19.6 µM and 7.3 µM, respectively.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Cianobactérias , Peptídeos Cíclicos/farmacologia , Animais , Antibacterianos/química , Antineoplásicos/química , Organismos Aquáticos , Artemia/efeitos dos fármacos , Linhagem Celular Tumoral , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Peptídeos Cíclicos/química , Pseudomonas aeruginosa/efeitos dos fármacos
12.
J Nat Prod ; 84(8): 2121-2128, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34445875

RESUMO

Peptide toxins find use in medicine, biotechnology, and agriculture. They are exploited as pharmaceutical tools, particularly for the investigation of ion channels. Here, we report the synthesis and activity of a novel family of peptide toxins: the cystine-knotted α nemertides. Following the prototypic α-1 and -2 (1 and 2), six more nemertides were discovered by mining of available nemertean transcriptomes. Here, we describe their synthesis using solid phase peptide chemistry and their oxidative folding by using an improved protocol. Nemertides α-2 to α-7 (2-7) were produced to characterize their effect on voltage-gated sodium channels (Blatella germanica BgNaV1 and mammalian NaVs1.1-1.8). In addition, ion channel activities were matched to in vivo tests using an Artemia microwell assay. Although nemertides demonstrate high sequence similarity, they display variability in activity on the tested NaVs. The nemertides are all highly toxic to Artemia, with EC50 values in the sub-low micromolar range, and all manifest preference for the insect BgNaV1 channel. Structure-activity relationship analysis revealed key residues for NaV-subtype selectivity. Combined with low EC50 values (e.g., NaV1.1: 7.9 nM (α-6); NaV1.3: 9.4 nM (α-5); NaV1.4: 14.6 nM (α-4)) this underscores the potential utility of α-nemertides for rational optimization to improve selectivity.


Assuntos
Peptídeos/farmacologia , Toxinas Biológicas/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Sequência de Aminoácidos , Animais , Artemia/efeitos dos fármacos , Baratas , Invertebrados/química , Dobramento de Proteína , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Canais de Sódio Disparados por Voltagem
13.
Acta Trop ; 223: 106102, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34416188

RESUMO

This research investigated the effect of the Croton rudolphianus leaf essential oil (EO) on Biomphalaria glabrata embryos (at different development stages) and adults, Schistosoma mansoni cercariae, and Artemia salina (non-target organism). It was possible to identify 31 compounds in the C. rudolphianus EO through GC-MS analysis. The major compounds from this oil were (E)-caryophyllene (17.33%), an unknown compound (16.87%), bicyclogermacrene (7.1%), δ-cadinene (6.62%) and germacrene D (5.38%). After incubation for 24 h, the EO of C. rudolphianus induced the occurrence of non-viable embryos (dead and malformed), with an LC50 value of 126.54, 133.51, 143.53 and 161.95 µg/mL and an LC90 value of 202.61, 216.48, 232.98 and 271.16 µg/mL to blastula, gastrula, trochophore and veliger embryonic stages, respectively. The EO was more effective against B. glabrata adults (LC50 and LC90 = 47.89 and 78.86 µg/mL, respectively), and S. mansoni cercariae (LC50 and LC90 = 14.81 and 22.15 after 120 mins of exposure, respectively) than against B. glabrata embryos. Concerning the micronucleus assay, the mean frequency of apoptosis, binucleation and micronucleus were 45.33 ± 3.51, 19.33 ± 1.53 and 0.67 ± 0.58 per 1000 cells at 25 µg/mL, which is the highest concentration tested. The oil killed A. salina with LC50 and LC90 values (68.33 and 111.5 µg/mL, respectively) higher than those determined for adult snails and S. mansoni cercariae. In conclusion, C. rudolphianus EO had a toxic effect against B. glabrata adults and embryos, and S. mansoni cercariae. Furthermore, this oil showed to be cytotoxic to hemocytes of B. glabrata. Concerning the non-target organism assay, C. rudolphianus EO was less toxic to A. salina then to adult snails and S. mansoni cercariae. Due to this, the EO from C. rudolphianus leaves is a potential alternative for schistosomiasis control.


Assuntos
Biomphalaria , Óleo de Cróton/farmacologia , Croton , Moluscocidas , Óleos Voláteis , Schistosoma mansoni/efeitos dos fármacos , Animais , Artemia/efeitos dos fármacos , Biomphalaria/efeitos dos fármacos , Croton/química , Óleos Voláteis/farmacologia , Folhas de Planta/química
14.
Chem Biodivers ; 18(9): e2100424, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216094

RESUMO

The present article investigates the chemical composition of volatiles of essential oil (EO) and headspace (HS) fraction, as well as biological activities of EO obtained from needles with twigs of Pseudotsuga menziesii var. menziesii cultivated in Serbia. The major class of compounds was monoterpene hydrocarbons with α-terpinolene, sabinene and ß-pinene (EO), and sabinene, α-terpinolene and ß-pinene (HS) as the dominant volatiles. Tested EO exhibited mostly low antimicrobial potential against investigated strains (ATCC and respiratory isolates), where MICs ranged 1.25-20.00 mg/mL. Nevertheless, based on presented results, where antimicrobial testing was done for the first time on human respiratory system isolates, there is a potential of this EO to be used as an adjuvant in the treatment of human respiratory infections, especially those caused by Pseudomonas aeruginosa or Candida albicans strains. Regarding toxicological evaluation, EO showed moderate toxicity in Artemia salina toxicity bioassay (LC50 =347.41, after 24 h) as well as week toxicity against Drosophila melanogaster with the ability only to moderately delay larval and pupal development.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Pseudotsuga/química , Compostos Orgânicos Voláteis/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Artemia/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Brotos de Planta/química , Pseudomonas aeruginosa/efeitos dos fármacos , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/isolamento & purificação
15.
Sci Rep ; 11(1): 13178, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162964

RESUMO

Among natural products, essential oils from aromatic plants have been reported to possess potent anticancer properties. In this work, we aimed to perform the cytotoxic concentration range screening and antiproliferative activity screening of chemically characterized Thymus vulgaris L. essential oil. In vivo bioassay was conducted using the brine shrimp lethality test (BSLT). In vitro evaluation of antiproliferative activity was carried out on three human tumor cell lines: breast adenocarcinoma MCF-7, lung carcinoma H460 and acute lymphoblastic leukemia MOLT-4 using MTT assay. Essential oil components thymol (36.7%), p-cymene (30.0%), γ-terpinene (9.0%) and carvacrol (3.6%) were identified by gas chromatography/mass spectrometry. Analyzed essential oil should be considered as toxic/highly toxic with LC50 60.38 µg/mL in BSLT and moderate/weakly cytotoxic with IC50 range 52.65-228.78 µg/mL in vitro, according to evaluated cytotoxic criteria. Essential oil induced a dose-dependent inhibition of cell proliferation in all tested tumor cell lines and showed different sensitivity. Dose dependent toxicity observed in bioassay as well as the in vitro assay confirmed that brine shrimp lethality test is an adequate method for preliminary toxicity testing of Thymus vulgaris L. essential oil in tumor cell lines.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Artemia/efeitos dos fármacos , Óleos Voláteis/toxicidade , Óleos de Plantas/toxicidade , Thymus (Planta)/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Artemia/crescimento & desenvolvimento , Bioensaio , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Cimenos/farmacologia , Cimenos/toxicidade , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Concentração Inibidora 50 , Larva/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Timol/farmacologia , Timol/toxicidade
16.
PLoS One ; 16(4): e0250118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33930032

RESUMO

Many phytochemicals can affect the growth and development of plants and insects which can be used as biological control agents. In this study, different concentrations of crude, hexane, chloroform, butanol, and aqueous extracts of Euphorbia nivulia Buch.-Ham., an endemic plant of the Cholistan desert in South Punjab of Pakistan, were analysed for their chemical constituents. Their various concentrations were also tested for their phytotoxic and insecticidal potential against duckweed, Lemna minor L., and the dusky cotton bug, Oxycarenus hyalinipennis Costa. various polyphenols, i.e., quercetin, gallic acid, caffeic acid, syringic acid, coumaric acid, ferulic acid, and cinnamic acid were detected in different concentrations with different solvents during the phytochemical screening of E. nivulia. In the phytotoxicity test, except for 100 µg/mL of the butanol extract gave 4.5% growth regulation, no phytotoxic lethality could be found at 10 and 100 µg/mL of all the extracts. The highest concentration, 1000 µg/mL, of the chloroform, crude, and butanol extracts showed 100, 63.1, and 27.1% of growth inhibition in duckweed, respectively. In the insecticidal bioassay, the highest O. hyalinipennis mortalities (87 and 75%) were recorded at 15% concentration of the chloroform and butanol extracts of E. nivulia. In contrast, the lower concentrations of the E. nivulia extracts caused the lower mortalities. Altogether, these findings revealed that E. nivulia chloroform extracts showed significant phytotoxicity while all the extracts showed insecticidal potential. This potential can be, further, refined to be developed for bio-control agents.


Assuntos
Euphorbia/química , Euphorbia/metabolismo , Extratos Vegetais/farmacologia , Alcaloides , Animais , Araceae/efeitos dos fármacos , Araceae/metabolismo , Artemia/efeitos dos fármacos , Euphorbia/fisiologia , Hemípteros/efeitos dos fármacos , Heterópteros/efeitos dos fármacos , Hexanos , Inseticidas/farmacologia , Paquistão , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo
17.
Bioorg Med Chem Lett ; 38: 127860, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33636301

RESUMO

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate. Furthermore, the toxicity of the more potent compounds in the Artemia salina model and their cell viability using murine RAW 264.7 cells is reported. The fluorinated compound 10k becomes a reliable candidate since it reduced the TPA-induced edema to 92%, lacked cytotoxicity against murine macrophages, and had minimal toxicity in Artemia salina.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Artemia/efeitos dos fármacos , Difenilamina/farmacologia , Edema/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Sobrevivência Celular/efeitos dos fármacos , Difenilamina/síntese química , Difenilamina/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Interações Hidrofóbicas e Hidrofílicas , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Células RAW 264.7 , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol/análogos & derivados
18.
Chem Biodivers ; 18(4): e2000982, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33587821

RESUMO

Bignonia nocturna (Bignoniaceae) is a plant used for medicinal purposes by the Amazonian indigenous peoples. To date, there have been no reported studies on its toxicity. The present study aimed to evaluate the chemical composition of essential oils obtained from Bignonia nocturna by different extraction techniques. In addition, an in silico study of the molecular interactions was performed using molecular docking and molecular dynamics. The extractions were carried out by hydrodistillation, simultaneous distillation-extraction, and steam distillation, using samples collected from the Amazon in summer and winter. The chemical composition was analyzed by GC/FID and GC/MS, and the cytotoxic activity in Artemia salina Leach was evaluated. The maximum yield (1.38 % w/w) was obtained by hydrodistillation. The results indicated that benzaldehyde predominated in all the fractions of both the volatile concentrate and the essential oils. In addition, the oil proved to be highly toxic to Artemia salina. The computer simulation results indicated that benzaldehyde strongly interacts with acetylcholinesterase, which is the likely interaction mechanism responsible for the cytotoxicity.


Assuntos
Artemia/efeitos dos fármacos , Bignoniaceae/química , Óleos Voláteis/toxicidade , Extratos Vegetais/toxicidade , Animais , Relação Dose-Resposta a Droga , Medicina Tradicional , Modelos Moleculares , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química
19.
PLoS One ; 16(2): e0247160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606769

RESUMO

Treatment with hydrogen peroxide (H2O2) raises the hatching rate through the development and diapause termination of Artemia cysts. To comprehend the upstream genetic regulation of diapause termination activated by exterior H2O2 elements, an Illumina RNA-seq analysis was performed to recognize and assess comparative transcript amounts to explore the genetic regulation of H2O2 in starting the diapause termination of cysts in Artemia salina. We examined three groupings treated with no H2O2 (control), 180 µM H2O2 (low) and 1800 µM H2O2 (high). The results showed a total of 114,057 unigenes were identified, 41.22% of which were functionally annotated in at least one particular database. When compared to control group, 34 and 98 differentially expressed genes (DEGs) were upregulated in 180 µM and 1800 µM H2O2 treatments, respectively. On the other hand, 162 and 30 DEGs were downregulated in the 180 µM and 1800 µM H2O2 treatments, respectively. Cluster analysis of DEGs demonstrated significant patterns among these types of 3 groups. GO and KEGG enrichment analysis showed the DEGs involved in the regulation of blood coagulation (GO: 0030193; GO: 0050818), regulation of wound healing (GO:0061041), regulation of hemostasis (GO: 1900046), antigen processing and presentation (KO04612), the Hippo signaling pathway (KO04391), as well as the MAPK signaling pathway (KO04010). This research helped to define the diapause-related transcriptomes of Artemia cysts using RNA-seq technology, which might fill up a gap in the prevailing body of knowledge.


Assuntos
Artemia/genética , Diapausa/genética , Embrião não Mamífero/metabolismo , Perfilação da Expressão Gênica , Peróxido de Hidrogênio/toxicidade , Animais , Artemia/efeitos dos fármacos , Diapausa/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Ontologia Genética , Anotação de Sequência Molecular , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
20.
Anticancer Agents Med Chem ; 21(18): 2603-2609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390141

RESUMO

BACKGROUND: Chemical synthesis methods are adverse in the medicinal field as they produce toxins on the surface area whereas green synthesis provide advancement are cost effective, environment friendly, can be easily scaled up for large scale synthesis. Silver and silver nanoparticles have an important application in the medical industry, such as tropical ointments which are used to prevent infection against burn and open wounds. There is no report on the green synthesis from Phlebodium aureum (L.) J. Smith. OBJECTIVE: The present study was aimed to synthesize silver nano-particles using Phlebodium aureum (L.) J. Smith extracts by green approach and to screen their cytotoxicity. METHODS: The synthesized AgNPs of P. aureum were characterized by FT-IR, SEM and XRD. The cytotoxicity of the aqueous extracts and AgNPs of P. aureum was determined. RESULTS: The silver nanoparticle synthesis was confirmed by color change from yellow to dark brown and absorption peak at 460 nm. FT-IR analysis confirmed the capping by proteins and other metabolites. XRD analysis confirmed the existence of silver nanaoparticles with a peak at 46.253°. The dose dependent cytotoxicity was observed in the aqueous and silver nanoparticles of P.aureum. CONCLUSION: The present study gave a simple and cheap route to synthesize the AgNPs using aqueous extracts of P. aureum. The studied extracts of P. aureum can be considered as a promising candidate for a plant-derived anti-tumour compound.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Polypodiaceae/química , Prata/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Artemia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Prata/química , Prata/isolamento & purificação , Células Tumorais Cultivadas
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