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1.
Nat Prod Res ; : 1-5, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867712

RESUMO

Two new alkenyl phenol derivatives, namely pestalol F (1) and pestalol G (2), along with two known compounds, pestalachloride A (3) and pestalotiopsin J (4), were isolated from the culture of the fungus Pestalotiopsis clavata JSQ 12. The structures of these compounds were primarily elucidated by MS, NMR and specific rotation data analysises. These secondary metabolites of Pestalotiopsis clavata were reported for the first time. Compound 2 displayed interesting cytotoxic activity against MCF-7 cell line with the IC50 value of 29.16 µM, whereas compound 3 exhibited moderate activity towards A549 cell line with the IC50 value of 35.71 µM. The positive control 5-FU showed cytotoxic effects on MCF-7 and A549 cell lines with the respective IC50 values of 26.70 and 26.07 µM. Compounds 1 and 2 displayed mild antibacterial activities against Staphylococcus aureus with MIC values of 128 and 64 µg/mL (MIC of positive control, penicillin, was 0.016 µg/mL), respectively.

2.
Int J Mol Sci ; 24(14)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37511122

RESUMO

In this study, we have found two peptides of Tag7 (PGLYRP1) protein-17.1A (HRDVQRT) and 17.1B (RSNYVLKG), that have different affinities to the TNFR1 receptor and the Hsp70 protein. Peptide 17.1A is able to inhibit signal transduction through the TNFR1 receptor, and peptide 17.1B can activate this receptor in a complex with Hsp70. Thus, it is possible to modulate the activity of the TNFR1 receptor and further perform its specific inhibition or activation in the treatment of various autoimmune or oncological diseases.


Assuntos
Citocinas , Neoplasias , Receptores Tipo I de Fatores de Necrose Tumoral , Humanos , Apoptose , Citocinas/metabolismo , Imunidade Inata , Peptídeos/farmacologia , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa
3.
J Environ Health Sci Eng ; 21(1): 73-83, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37159741

RESUMO

The final and most crucial step in obtaining clean water is disinfection. More innovative methods of water disinfection have recently been sought. Water disinfection is a promising application for nanoparticles as disinfectants. As a contribution to the literature, biofilm and metal-containing nanoparticles as antiadhesion inhibitors were used in conjunction with ultrasound in this study. The microbroth dilution test was used to reveal the microbiological antibacterial activities of different concentrations of AgNO3 and CuCl2 containing nanoparticles against the Escherichia coli ATCC 25,922 strain, which is an indicator bacterium in water systems. Antibiofilm activities were then investigated using biofilm attachment and biofilm inhibition tests. The inhibitory effect of nanoparticle ultrasonic waves on biofilm contamination was determined using a novel approach. Human keratinocyte cells (HaCaT cell line) were used in cell culture studies after water disinfection, and their cytotoxic effects were demonstrated using the MTT assay. The findings suggest that the nanoparticles utilized might be a viable choice for water disinfection applications. Furthermore, employing ultrasound at low doses with nanoparticles resulted in greater results. One feasible option is to employ nanoparticles to cleanse water without producing cytotoxicity.

4.
J Ethnopharmacol ; 312: 116493, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37054823

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lemon myrtle (Backhousia citriodora F.Muell.) leaves, whether fresh or dried, are used traditionally in folk medicine to treat wounds, cancers, skin infections, and other infectious conditions. However, the targets and mechanisms related to anti-cancer effect of lemon myrtle are unavailable. In our study, we found that the essential oil of lemon myrtle (LMEO) showed anti-cancer activity in vitro, and we initially explored its mechanism of action. MATERIALS AND METHODS: We analyzed the chemical compositions of LMEO by GC-MS. We tested the cytotoxicity of LMEO on various cancer cell lines using the MTT assay. Network pharmacology was used also to analyze the targets of LMEO. Moreover, the mechanisms of LMEO were investigated through scratch assay, flow cytometry analysis, and western blot in the HepG2 liver cancer cell line. RESULTS: LMEO showed cytotoxicity on various cancer cell lines with values of IC50 40.90 ± 2.23 (liver cancer HepG2 cell line), 58.60 ± 6.76 (human neuroblastoma SH-SY5Y cell line), 68.91 ± 4.62 (human colon cancer HT-29 cell line) and 57.57 ± 7.61 µg/mL (human non-small cell lung cancer A549 cell line), respectively. The major cytotoxic chemical constituent in LMEO was identified as citrals, which accounted for 74.9% of the content. Network pharmacological analysis suggested that apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1), androgen receptor (AR), cyclin-dependent kinases 1 (CDK1), nuclear factor erythroid 2-related factor 2 (Nrf-2), fatty acid synthase (FASN), epithelial growth factor receptor (EGFR), estrogen receptor 1 (ERα) and cyclin-dependent kinases 4 (CDK4) are potential cytotoxic targets of LMEO. These targets are closely related to cell migration, cycle and apoptosis. Notley, the p53 protein had the highest confidence to co-associate with the eight common targets, which was further confirmed by scratch assay, flow cytometry analysis, and western blot in the HepG2 liver cancer cell line. LMEO significantly inhibited the migration of HepG2 cells in time-dependent and dose-dependent manner. Moreover, LMEO caused a S-phase blocking on HepG2 cells and promoted apoptosis in the meanwhile. Western blot results indicated that p53 protein, Cyclin A2 and Bax proteins were up-regulated, while Cyclin E1 and Bcl-2 proteins were down-regulated. CONCLUSION: LMEO showed cytotoxicity in various cancer cell lines in vitro. Pharmacological networks showed LMEO to have multi-component and multi-targeting effects that are related to inhibit migration of HepG2 cells, and affect cell cycle S-phase arrest and apoptosis through modulation of p53 protein.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Hepáticas , Neoplasias Pulmonares , Myrtaceae , Myrtus , Neuroblastoma , Óleos Voláteis , Humanos , Células Hep G2 , Proteína Supressora de Tumor p53/metabolismo , Óleos Voláteis/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Apoptose , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/farmacologia , Ciclinas/metabolismo , Ciclinas/farmacologia , Ciclinas/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células
5.
Molecules ; 27(6)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35335127

RESUMO

In an attempt to explore the bioactive metabolites of the soft coral Sarcophyton cinereum, three new cembranolides, cinerenolides A-C (1-3), and 16 known compounds were isolated and identified from the EtOAc extract. The structures of the new cembranolides were elucidated on the basis of spectroscopic analysis, and the NOE analysis of cinerenolide A (1) was performed with the assistance of the calculated lowest-energy molecular model. The relative configuration of cinerenolide C (3) was determined by the quantum chemical NMR calculation, followed by applying DP4+ analysis. In addition, the cytotoxic assays disclosed that some compounds exhibited moderate to potent activities in the proliferation of P388, DLD-1, HuCCT-1, and CCD966SK cell lines.


Assuntos
Antozoários , Antineoplásicos , Diterpenos , Animais , Antozoários/química , Antineoplásicos/química , Diterpenos/química , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular
6.
Artigo em Inglês | MEDLINE | ID: mdl-35094645

RESUMO

Novel 3'-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3'-deoxythymidine analogues (7a-l) were developed by the Cu alkyne-azide cycloaddition (CuAAC) reaction. The obtained lead compounds were confirmed by using 1H NMR, 13C NMR, 2 D NMR, HRMS and their anticancer activities were screened against Huh-7 liver cancer cells and U87MG human glioblastoma cells. Among the synthesized fluorinated 1,2,3-triazolyl nucleosides, three compounds (7i, 7a-b) demonstrated promising anti-proliferative against Huh-7 and U87MG cell lines. Significantly, compound 7i has displayed remarkable promising anticancer activity with IC50 value in the micromole range (22.41-24.92 µM) and (18.12-21.36 µM) against Huh-7 cancer cells and U87MG glioblastoma cells, respectively.


Assuntos
Antineoplásicos , Glioblastoma , Timidina , Triazóis , Antineoplásicos/química , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Humanos , Relação Estrutura-Atividade , Timidina/análogos & derivados , Timidina/química , Triazóis/química
7.
Fitoterapia ; 156: 105089, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34800595

RESUMO

Eight previously undescribed compounds, two quinones (1-2), one sesquiterpene (3), and five phenol compounds (4-8), including three enantiomers (6a, 7a, and 8a), along with three corresponding known enantiomers (6b-8b) were isolated from the aerial parts of Morinda umbellata L. Their structures were elucidated by 1D and 2D NMR spectroscopy, X-ray diffraction, and experimental and calculated ECD spectra, respectively. Compound 5 was found to have weak cytotoxity, which inhibited the growth of seven human cancer cell lines (A2780, HeLa, MCF-7, BGC-823, H7420, Ketr3 and SW 1990) with IC50 values from 13.3 to 15.1 µM.


Assuntos
Citotoxinas/toxicidade , Morinda/química , Fenóis/toxicidade , Quinonas/toxicidade , Sesquiterpenos/toxicidade , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Citotoxinas/isolamento & purificação , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Fenóis/isolamento & purificação , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Quinonas/isolamento & purificação , Sesquiterpenos/isolamento & purificação
8.
Macromol Biosci ; 22(6): e2100318, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34773451

RESUMO

Cellulose nanocrystal (CNC) is the rod-like nano-object derived from natural cellulose with the features of low toxicity and good biocompatibility, widely used as the functional additive and nanomaterial in the biomedicine. Two negatively charged cellulose nanocrystals, CNC and TO-CNC (surface oxidized CNC), are prepared by the sulfuric acid hydrolysis and further surface oxidization. Based on electrostatic adsorption, five trace metal elements (TMEs) including cobalt (Co), nickel (Ni), manganese (Mn), lead (Pb), and cadmium (Cd) are loaded on the surface of two nanocrystals as the biocompatible nanocarriers. The adsorbed contents of TMEs on two nanocrystals are affected by their surface charge densities and the complexes can keep stability under three varied pH conditions. Two cell lines, viz. human nasopharyngeal cancer cell and normal human bronchial epithelial cell, are selected for the investigation of cytotoxity of these TME-loaded nanocrystals at the concentration range of 0.1-500 µg mL-1 . The high concentrations of TME-loaded nanocrystals will induce the inhibition of cells activity and proliferation, particularly for Pb2+ - and Cd2+ -loaded nanocrystals. The cancer cell generally exhibits more sensitivity of cytotoxity to these metal elements than the normal cell, which may be potentially used as the activity inhibitor for specific cells in the future study.


Assuntos
Nanopartículas , Neoplasias Nasofaríngeas , Adsorção , Cádmio , Celulose/química , Humanos , Chumbo , Nanopartículas/química , Eletricidade Estática
9.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299072

RESUMO

Five new compounds, eupatodibenzofuran A (1), eupatodibenzofuran B (2), 6-acetyl-8-methoxy-2,2-dimethylchroman-4-one (3), eupatofortunone (4), and eupatodithiecine (5), have been isolated from the aerial part of Eupatorium fortunei, together with 11 known compounds (6‒16). Compounds 1 and 2 featured a new carbon skeleton with an unprecedented 1-(9-(4-methylphenyl)-6-methyldibe nzo[b,d]furan-2-yl)ethenone. Among the isolates, compound 1 exhibited potent inhibitory activity with IC50 values of 5.95 ± 0.89 and 5.55 ± 0.23 µM, respectively, against A549 and MCF-7 cells. The colony-formation assay demonstrated that compound 1 (5 µM) obviously decreased A549 and MCF-7 cell proliferation, and Western blot test confirmed that compound 1 markedly induced apoptosis of A549 and MCF-7 cells through mitochondrial- and caspase-3-dependent pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Eupatorium/química , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Acetofenonas/química , Antineoplásicos Fitogênicos/química , Apoptose , Benzofuranos/química , Proliferação de Células , Cromonas/química , Humanos , Estrutura Molecular , Neoplasias/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas
10.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068559

RESUMO

Cu-catalyzed 1,3-dipolar cycloaddition of methyl 2-azidoacetate to iodobuta-1,3-diynes and subsequent Suzuki-Miyaura cross-coupling were used to synthesize new triazoles derivatives: 5-aryl-4-arylethynyl-1H-1,2,3-triazoles. Investigation of their optical properties by using UV absorption and fluorescence emission spectroscopies revealed that all molecules possess fluorescence properties with the values of the Stokes shift more than 100 nm. The photophysical behavior of the two most promising triazoles in polar and non-polar solvents was also studied.


Assuntos
Luz , Fenômenos Físicos , Triazóis/síntese química , Triazóis/farmacologia , Células HEK293 , Células HeLa , Humanos , Conformação Molecular , Solventes , Espectrometria de Fluorescência , Triazóis/química
11.
Phytochemistry ; 187: 112705, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33957541

RESUMO

Phytochemical study on the ethanolic extract of the dried roots of Ferula samarkandica Korovin led to the isolation of nine undiscribed sesquiterpene coumarins, samarcandicins A-I, along with thirteen known sesquiterpene coumarins. Their structures were characterized by detailed spectroscopic analysis including NMR and HR-ESI-MS. Mogoltacin and nevskin exhibited high inhibitory activity against MV-4-11 cell with IC50 values of 3.94 ±â€¯0.06 µM and 3.87 ±â€¯0.10 µM, respectively, and nevskin and feshurin showed high inhibitory activity against mino cell with IC50 values of 1.48 ±â€¯0.06 µM and 7.88 ±â€¯0.60 µM, respectively.


Assuntos
Ferula , Sesquiterpenos , Cumarínicos/farmacologia , Estrutura Molecular , Raízes de Plantas , Sesquiterpenos/farmacologia
12.
Nat Prod Res ; 35(21): 3535-3539, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31979990

RESUMO

As part of our search for compounds with cytotoxicity from endophytes of traditional Chinese medicines, two novel nor-sesquiterpenoids (1-2) with a new skeleton containing a tetrahydrofuran moiety were isolated form a rice medium of Fusarium tricinctum, an endophytic fungus isolated from the root of Ligusticum chuanxiong. The structures of these two previously undescribed compounds were elucidated by interpretation of the spectroscopic evidences including NMR correlations as well as MS data. The absolute configurations of these two compounds were confirmed by TD-DFT-ECD calculations. An MTT assay indicated that compound 1 exhibited moderate cytotoxic activity against MV4-11 with an IC50 value of 22.29 µM.


Assuntos
Fusarium , Ligusticum , Sesquiterpenos , Endófitos , Fungos
13.
Artigo em Chinês | MEDLINE | ID: mdl-32746567

RESUMO

Objective: To study the toxicity of dioctyl phthalate (DOP) on adrenal pheochromocytoma (PC12) cells and its effect on processing of amyloid precursor protein (APP) -enzymolysis. Methods: In vitro experiments, PC12 cells were divided into blank control (CT) , low DOP (DOP1) , medium DOP (DOP2) , high DOP (DOP3) , low DOP+Aß(25-35) (DOP1+Aß) , medium DOP+Aß(25-35) (DOP2+Aß) , high DOP+Aß(25-35) (DOP3+Aß) , Aß(25-35) (Aß) , a total of 8 groups, each with 4 samples. The cell viability was measured by MTT assay, the contents of lactate dehydrogenase (LDH) , malondialdehyde (MDA) and nitric oxide (NO) were measured, and cysteine protease 3 (Caspase-3) was determined by Western blot. In the transfection experiment, the hamster ovary (CHO) cells were transfected with APP695 and treated with different concentrations of DOP. They were divided into V-Flag control (V-Flag) , APP695-Flag (APP695) , low DOP (DOP1+APP695) , medium DOP (DOP2+APP695) , high DOP (DOP3+APP695) , a total of 5 groups, each with 4 samples. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of Aß(1-40) and the activity of γ-secretase. In vivo experiment, 50 male Kunming mice of SPF grade, weighing (20±2) g, were selected and randomly divided into control, lead (Pb) , low DOP (DOP1') , medium DOP (DOP2') , high DOP (DOP3') consisted of 5 groups, each with 10 mice, continuously gavage for 6 weeks. Morris water maze method was used to detect the effect of different concentrations of DOP on learning and memory in mice, and ELISA method was used to detect ß-secretase, γ-secretase activity and Aß(1-40) content in brain tissue. Results: Compared with the CT group, the cell viabilities of the DOP2 and DOP3 groups were decreased, and the contents of LDH, MDA, and NO were increased, and the differences were statistically significant (P<0.05) . Compared with the CT group, the cell viabilities of DOP1+Aß, DOP2+Aß and DOP3+Aß groups were decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant (P<0.05) . Compared with the Aß group, the cell viability of DOP3+Aß group was decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant (P<0.05) . Compared with the Aß group, the contents of LDH and NO in the DOP2+Aß group were increased, and the differences were statistically significant (P<0.05) . Compared with the CT group, the expression levels of Caspase-3 in the DOP2 and DOP3 groups were increased, and the differences were statistically significant (P<0.05) . Compared with the Aß group, the expression levels of Caspase-3 in the DOP2+Aß and DOP3+Aß groups were increased, and the differences were statistically significant (P<0.05) . Compared with the APP695 group, the contents of Aß(1-40) and the activities of γ-secretase of the DOP2+APP695 and DOP3+APP695 groups were increased (P<0.05) . Compared with the control group, the activities of ß-secretase, γ-secretase and the content of Aß(1-40) in the brain tissue of DOP3'group were increased, and the differences were statistically significant (P<0.05) . Compared with the Pb group, the activities of ß-secretase, γ-secretase and the content of Aß(1-40) of the DOP3'group were increased, and the differences were statistically significant (P<0.05) . Compared with the control group, the target quadrant stay time and the number of crossings in the DOP2'and DOP3'groups were reduced, and the differences were statistically significant (P<0.05) . Conclusion: DOP has a certain toxic effect on PC12 cells, causing learning and memory impairment in mice, and may promote the pathological progression of Alzheimer's disease.


Assuntos
Precursor de Proteína beta-Amiloide , Dietilexilftalato/toxicidade , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides , Animais , Cricetinae , Masculino , Memória , Camundongos , Células PC12 , Ratos
14.
Bioprocess Biosyst Eng ; 43(10): 1791-1800, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32424693

RESUMO

Abiotic iron monosulfide (FeS) has attracted growing interests in dechlorinating trichloroethylene (TCE) in anoxic groundwater, but it is still unclear how biogenic FeS affects the dechlorination and thus the cytotoxity of TCE. In this work, a biogenic FeS was synthesized by Shewanella oneidensis MR-1 with addition of ferrihydrite and S0, and it was used for dechlorination of TCE in alkaline environment and the de-cytotoxicity was evaluated by the growth of Synechocystis sp. PCC6803. The results show that the biogenic FeS was of mackinawite, with a loose flower-like mosaic structure. The dechlorination of TCE by the biogenic FeS was accelerated by 6 times than that by abiotic FeS. TCE was dechlorinated mainly by hydrogenolysis to form dichloroethane (C2H2Cl2), vinyl chloride (C2H3Cl), and finally ethylene, accompanied with transformation of both Fe2+ to Fe3+ and monosulfide to disulfide and polysulfide on the biogenic FeS surface. The concentration for 50% of maximal inhibition effect (EC50) of TCE to Synechocystis was 486 mg/L and the inhibition to Synechocystis under the EC50 was relieved more significantly on addition of the biogenic FeS than that of abiotic FeS. These results indicate that the biogenic FeS promoted the dechlorination and thus de-cytotoxity of TCE.


Assuntos
Compostos Ferrosos/metabolismo , Shewanella/metabolismo , Tricloroetileno/metabolismo , Poluentes Químicos da Água/metabolismo
15.
Fitoterapia ; 145: 104573, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32222428

RESUMO

Three undescribed azaphilones, phomopsones A-C (1-3) and two known azaphilones (4-5) were isolated from the culture of endophytic fungus Phomopsis sp. CGMCC No.5416 from the stems of Achyranthes bidentata. Their structures were determined by spectroscopic analysis (HRESIMS, 1D and 2D NMR), and the absolute configurations were determined by CD spectroscopy. Compounds 2 and 3 showed significant inhibitory activities against HIV-1 with against HIV-1 with IC50 values of 7.6 and 0.5 µmol/L, respectively. Compounds 2 and 3 also displayed moderate cytotoxicity with CC50 values of 3.2-303 µmol/L against A549, MDA-MB-231 and PANC-1 cell lines. Moreover, compound 3 can induce the early apoptosis of PANC-1 cancer cells with the apoptosis rate of 28.54%.


Assuntos
Fármacos Anti-HIV/farmacologia , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Phomopsis/química , Pigmentos Biológicos/farmacologia , Achyranthes/microbiologia , Fármacos Anti-HIV/isolamento & purificação , Antineoplásicos/isolamento & purificação , Apoptose , Benzopiranos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , China , Endófitos/química , HIV-1/efeitos dos fármacos , Humanos , Estrutura Molecular , Pigmentos Biológicos/isolamento & purificação , Caules de Planta/microbiologia
16.
Molecules ; 24(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618846

RESUMO

KTTKS is a matrikine that originates from the proteolytic hydrolysis of collagen. This peptide stimulates ECM production and types I and III collagen expression in vitro. A more stable form of KTTKS is pal-KTTKS, known as Matrixyl® or palmitoyl pentapeptide-3. A series of novel pentapeptides, analogues of KTTKS with the general formula X-KTTKS-OH(NH2), where X = acetyl, lipoyl, palmitoyl residues, was designed and synthesized. Their effect on amidolytic activity of urokinase, thrombin, trypsin, plasmin, t-PA, and kallikrein were tested. Cytotoxic tests on fibroblasts, as well as collagen and DNA biosynthesis tests for selected peptides, were also carried out. The test results showed that the most active plasmin inhibitors were palmitoyl peptides, whether in acid or amide form. No biological effects of lysine modification to arginine in the synthesized peptides were found. None of the synthesized peptides was not cytotoxic on fibroblasts, and three of them showed cell growth. These three compounds showed no concentration-activity relationship in the collagen and DNA biosynthesis assays.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Células Cultivadas , Colágeno/biossíntese , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Concentração Inibidora 50 , Peptídeos/química , Peptídeos/farmacologia , Proteólise/efeitos dos fármacos
17.
Clin Immunol ; 202: 40-48, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30914281

RESUMO

γδ T cells are a unique population of lymphocytes that have regulatory roles in patients with chronic hepatitis B (CHB); however, their role in acute hepatitis B (AHB) infection remains unclear. Phenotype and function of γδ T cells were analyzed in 29 AHB patients, 28 CHB patients, and 30 healthy controls (HCs) using immunofunctional assays. Compared with HCs and CHB patients, decreased peripheral and increased hepatic γδ T cells were found in AHB patients. Increased hepatic γδ T cells in AHB patients were attributed to elevated hepatic chemokine levels. Peripheral γδ T cells exhibited highly activated and terminally differentiated memory phenotype in AHB patients. Consistently, peripheral γδ T cells in AHB patients showed increased cytotoxic capacity and enhanced antiviral activity which was further proved in longitudinal study. Activated γδ T cells in AHB patients exhibited increased cytotoxicity and capacity for viral clearance associated with liver injury and the control of infection.


Assuntos
Hepatite B/imunologia , Linfócitos Intraepiteliais/imunologia , Doença Aguda , Adolescente , Adulto , Quimiocinas/imunologia , Doença Crônica , DNA Viral/análise , Feminino , Hepatite B/virologia , Vírus da Hepatite B/genética , Humanos , Fígado/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Phytomedicine ; 57: 262-270, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802712

RESUMO

BACKGROUND: Leishmaniasis is a disease caused by protozoan parasites of the Leishmania genus whose current treatment has high cost, highly toxic, and difficult administration, which makes it very important to find alternative natural compounds of high efficiency and low cost. PURPOSE: This study assessed the in vitro effect of caffeic acid (CA) on promastigotes and L. amazonensis-infected macrophages. METHODS: Evaluation of the in vitro leishmanicidal activity of CA against promastigotes and L. amazonensis infected peritoneal macrophages, as well its microbicide mechanisms. RESULTS: CA 12.5-100 µg/ml were able to inhibit promastigotes proliferation at all tested periods. The IC50, 12.5 µg/ml, also altered promastigote cell morphology and cell volume accompanied by loss of mitochondrial integrity, increase in reactive oxygen species (ROS) production, phosphatidylserine exposure, and loss of plasma membrane integrity - characterizing the apoptosis-like process. Moreover, CA reduced the percentage of infected macrophages and the number of amastigotes per macrophages increasing TNF-α, ROS, NO and reducing IL-10 levels as well as iron availability. CONCLUSION: CA showed in vitro antipromastigote and antiamostigote by increasing oxidant and inflammatory response important to eliminate the parasite.


Assuntos
Antiprotozoários/farmacologia , Ácidos Cafeicos/farmacologia , Leishmania/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Ferro/metabolismo , Leishmania/patogenicidade , Leishmania/fisiologia , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Fosfatidilserinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
J Nat Med ; 73(1): 131-145, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30327993

RESUMO

A search for cytotoxic cholestane glycosides from Ornithogalum saundersiae bulbs resulted in the isolation of three new OSW-1 analogues (1-3), a new cholestane bisdesmoside (4), a 5ß-cholestane diglycoside (5), and four new 24(23 → 22)-abeo-cholestane glycosides (6-9), together with 11 known cholestane glycosides (10-20), including OSW-1 (11). The structures of 1-9 were determined based on conventional spectroscopic analysis and chemical evidence. As expected, based on previous data, 1-3 exhibited potent cytotoxic activity against HL-60 human promyelocytic leukemia cells and A549 human lung adenocarcinoma cells. Furthermore, the ability of OSW-1 to induce apoptosis in HL-60 cells was examined. Aggregation of nuclear chromatin, accumulation of the sub-G1 cells, DNA fragmentation, and caspase-3 activation were assessed in HL-60 cells treated with OSW-1, providing evidence for OSW-1-induced apoptosis in HL-60 cells. No mitochondrial membrane potential or release of cytochrome c into the cytoplasm were observed in the OSW-1-treated apoptotic HL-60 cells, indicating that a mitochondria-independent signaling pathway is involved in apoptotic cell death.


Assuntos
Colestanos/química , Colestenonas/metabolismo , Glicosídeos/química , Células HL-60/metabolismo , Mitocôndrias/metabolismo , Ornithogalum/química , Saponinas/metabolismo , Apoptose , Humanos , Transdução de Sinais
20.
Invest New Drugs ; 37(4): 602-615, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30155717

RESUMO

Cervical cancer is the third most commonly diagnosed tumor type and the fourth cause of cancer-related death in females. Therapeutic options for cervical cancer patients remain very limited. Annona crassiflora Mart. is used in traditional medicine as antimicrobial and antineoplastic agent. However, little is known about its antitumoral properties. In this study the antineoplastic effect of crude extract and derived partitions from A. crassiflora Mart in cervical cancer cell lines was evaluated. The crude extract significantly alters cell viability of cervical cancer cell lines as well as proliferation and migration, and induces cell death in SiHa cells. Yet, the combination of the crude extract with cisplatin leads to antagonistic effect. Importantly, the hexane partition derived from the crude extract presented cytotoxic effect both in vitro and in vivo, and initiates cell responses, such as DNA damage (H2AX activity), apoptosis via intrinsic pathway (cleavage of caspase-9, caspase-3, poly (ADP-ribose) polymerase (PARP) and mitochondrial membrane depolarization) and decreased p21 expression by ubiquitin proteasome pathway. Concluding, this work shows that hexane partition triggers several biological responses such as DNA damage and apoptosis, by intrinsic pathways, and was also able to promote a direct decrease in tumor perimeter in vivo providing a basis for further investigation on its antineoplastic activity on cervical cancer.


Assuntos
Annona , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Dano ao DNA , Feminino , Hexanos/química , Humanos , Neovascularização Patológica/tratamento farmacológico , Folhas de Planta , Solventes/química , Neoplasias do Colo do Útero/patologia
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