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1.
Food Chem ; 312: 126089, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31896452

RESUMO

A fluorometric and colorimetric dual-mode sensing platform based on graphitic carbon nitrite quantum dots (g-CNQDs) and Fe (II)-bathophenanthroline complex (BPS-Fe2+) was designed to the sensitive detection of nitrite (NO2-) in sausage and water. In this system, the fluorescence of g-CNQDs was quenched by BPS-Fe2+ complex due to the inner filter effect (IFE). When NO2- was present, Fe2+ was oxidized by nitrite to form BPS-Fe3+ complex with BPS, leading to the recovery of the fluorescence from g-CNQDs. Therefore, we constructed a "turn-off-on" fluorescence probe for detection of NO2-. Moreover, with the increase of NO2- concentration, the color of the solution changed from red to colorless, so the UV-vis measurements and on-site visual detection were realized. The method is capable of detecting NO2- in the concentration range of 2.32-34.8 µM with good selectivity and high sensitivity. In addition, the method has the potential to determine NO2- in water samples and sausage samples.


Assuntos
Carbono/química , Grafite/química , Produtos da Carne/análise , Nitritos/química , Fenantrolinas/química , Pontos Quânticos , Água/química , Colorimetria , Fluorescência , Corantes Fluorescentes , Fluorometria , Compostos de Ferro/química
2.
Chem Asian J ; 15(1): 85-90, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31729130

RESUMO

We recently found that [Eu(pda)2 ]- (pda: 1,10-phenanthroline-2,9-dicarboxylic acid), which has an achiral structure in crystals, exhibits circularly polarized luminescence (CPL) in aqueous solutions containing chiral amino acids such as arginine and histidine. CPL measurements were performed for agar gel, which includes an aqueous solution of [Eu(pda)2 ]- and chiral arginine or histidine. The spectral shape, concentration, and pH dependences on CPL intensity in the agar gels were very close to those in aqueous solutions, indicating that the CPL of the EuIII complex in the agar gels was induced by mechanism similar to that in aqueous solutions. We performed spatially resolved CPL measurements using a laboratory-built microscopic CPL spectroscopic system for agar-gel samples, where d- and l- amino acids were separately dispersed. We successfully recorded CPL imaging maps showing spatial dispersions of d- and l-amino acid in the agar gels.


Assuntos
Ágar/química , Arginina/análise , Complexos de Coordenação/química , Európio/química , Histidina/análise , Fenantrolinas/química , Géis/química , Concentração de Íons de Hidrogênio , Medições Luminescentes/instrumentação , Estrutura Molecular
3.
Talanta ; 206: 120250, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514846

RESUMO

The development of a simple and economical spectrophotometric system based on the use of a device created by 3D printing and the electronics necessary to control the intensity of the radiation source was described. The measurements are made with a low-cost digital webcam. The entire system is only powered through the USB outputs of a computer, which makes the portable and really practical system for the measurements in the field. This method was applied to determine iron (II) in waters using o-phenanthroline as chromogenic reagent giving a red complex, and also to hypochlorite determination using tetramethylbenzidine as the reagent providing a yellow color. The calibration curves were built using a mathematical algorithm making a RGB deconvolution. The intense of colors obtained from a webcam in each concentration of analyte had a relationship with the absorbance values. In order to confirm the accuracy and precision of this method, a traditional spectrophotometer was used for validation.


Assuntos
Computadores , Fotografação/instrumentação , Impressão Tridimensional , Espectrofotometria/instrumentação , Benzidinas/química , Calibragem , Ácido Hipocloroso/análise , Ferro/análise , Limite de Detecção , Fenantrolinas/química , Espectrofotometria/métodos
4.
Neurochem Res ; 44(9): 2156-2169, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31414344

RESUMO

Copper oxide nanoparticles (CuO-NPs) dispersions are known for their high cell toxic potential but contaminating copper ions in such dispersions are a major hurdle in the investigation of specific nanoparticle-mediated toxicity. In order to distinguish between the adverse effects exhibited by CuO-NPs and/or by contaminating ionic copper, the membrane-impermeable copper chelator bathocuproine disulfonate (BCS) was added in a low molar ratio (20% of the total copper applied) in order to chelate the copper ions that had been released extracellularly from the CuO-NPs before or during the incubation. Physicochemical characterization of synthesized CuO-NPs revealed that the presence of this low concentration of BCS did not alter the size or zeta potential of the CuO-NPs. Application of CuO-NPs to C6 glioma cells and primary astrocytes induced a concentration- and temperature-dependent copper accumulation which was accompanied by a severe loss in cell viability. The adverse consequences of the CuO-NP application were not affected by the presence of 20% BCS, while the copper accumulation and cell toxicity observed after application of ionic copper were significantly lowered in the presence of BCS. These results demonstrate that for the experimental conditions applied the adverse consequences of an exposure of cultured glial cells to dispersions of CuO-NPs are mediated by accumulated NPs and not caused by the uptake of contaminating copper ions.


Assuntos
Cobre/toxicidade , Nanopartículas Metálicas/toxicidade , Neuroglia/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Quelantes/química , Cobre/química , Fenantrolinas/química , Ratos , Succímero/química
5.
Food Chem ; 298: 125049, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260998

RESUMO

Heavy traces metals may be present in honey being their detection very important for the quality control and it also serves as an indicator of environmental pollution. A new methodology for lead traces determination has been developed based on the quenching effect of the metal on fluorescent emission of 8-hydroxyquinoline and o-phenanthroline at λem = 360 nm (λexc = 250 nm). Experimental variables that influence on fluorimetric sensitivity were optimized by uni-variation assays. The calibration graph using zeroth order regression was linear from 0.105 µg L-1 to 51.8 µg L-1, with correlation coefficient better than 0.998. Under the optimal conditions, the limits of detection and quantification were of 0.035 µg L-1 and 0.105 µg L-1, respectively. The trueness of the methodology was assessed trough parallel samples analysis by ICP-MS. The proposed method showed good sensitivity, adequate selectivity with good tolerance to foreign ions, and was applied to the determination of lead trace amounts in honey from San Luis city (Argentina) with satisfactory results.


Assuntos
Fluorometria/métodos , Chumbo/análise , Estudos Transversais , Mel/análise , Concentração de Íons de Hidrogênio , Limite de Detecção , Oxiquinolina/química , Fenantrolinas/química , Reprodutibilidade dos Testes
6.
Talanta ; 204: 613-625, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357343

RESUMO

A modified CUPRAC (cupric reducing antioxidant capacity) method was developed for the simultaneous estimation of protein oxidation and counteracting antioxidant defense, and the results were compared with those of a modified 2,4-dinitrophenylhydrazine (DNPH) carbonyl assay. The alkaline carbonyl method was cleared off interferences by solvent extraction using a cationic surfactant. Both solution and Nafion membrane sensor CUPRAC methods were used to measure the oxidative hazard in protein solutions. Bovine serum albumin, fetal bovine serum and egg white were used as protein probes, exposed to oxidation by Fe(II)-induced Fenton reaction in the absence and presence of selected antioxidants (ascorbic acid, cysteine, gallic acid, glutathione, and N-acetyl cysteine). Protein probes were initially unreactive toward the CUPRAC and DNPH reagents, but produced colored products upon Fenton oxidation which were bleached by antioxidants, enabling an indirect measurement of antioxidant activity (AOA) by difference. Spearman's rank test for antioxidants demonstrated that there was a strong correlation (+0.7 to +0.9) between the modified CUPRAC and carbonyl assays. There was also a strong correlation between the results of the solution phase and optical sensing CUPRAC methods (R2 > 0.95). As opposed to conventional antioxidant assays not using biologically relevant probes, this work utilizes protein probes for AOA assessment.


Assuntos
Proteínas Sanguíneas/análise , Proteínas do Ovo/análise , Carbonilação Proteica , Soroalbumina Bovina/análise , Animais , Antioxidantes/química , Proteínas Sanguíneas/química , Bovinos , Citrus sinensis , Colorimetria/métodos , Cobre/química , Proteínas do Ovo/química , Sucos de Frutas e Vegetais , Hidrazinas/química , Fenantrolinas/química , Aves Domésticas , Soroalbumina Bovina/química
7.
Dalton Trans ; 48(32): 12257-12271, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31339136

RESUMO

Of late, cancer has become a terrible disease affecting people throughout the world. Keeping this in mind, we tried to design drugs that are more lipophilic, target-specific, water-soluble, cytoselective and fluorescent. In this regard, we reported novel ruthenium(ii)-p-cymene imidazophenanthroline scaffolds as effective DNA targeting agents. The planarity of imidazophenanthroline ligands caused the Ru(ii) complex to be a good intercalator. An extended π-electronic conjugation was introduced in the imidazophenanthroline moieties through the Suzuki and Sonogashira coupling reactions. Here, we synthesized nine Ru(ii) complexes (16a-b, 17a-d, and 19a-c). Among these, [(η6-p-cymene)RuCl(K2-N,N-2-(4'-methyl-[1,1'-BIphenyl]-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline)]·PF6 (16b) exhibited the best potency and selectivity with excellent cellular uptake; [(η6-p-cymene)RuCl(K2-N,N-2-(4-(phenylethynyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline)]·PF6 (17a) acted as a cytoselective probe for live cell imaging.


Assuntos
Antineoplásicos/análise , Complexos de Coordenação/análise , Substâncias Luminescentes/análise , Imagem Óptica , Fenantrolinas/análise , Rutênio/análise , Antineoplásicos/síntese química , Antineoplásicos/química , Sobrevivência Celular , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Ligantes , Substâncias Luminescentes/síntese química , Substâncias Luminescentes/química , Estrutura Molecular , Fenantrolinas/química , Rutênio/química , Relação Estrutura-Atividade
8.
Molecules ; 24(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195716

RESUMO

We describe the screening of a set of cryptopleurine derivatives, namely thienoquinolizidine derivatives and (epi-)benzo analogs with bioactive phenanthroquinolizidine alkaloids that induce cytotoxic effects in the mouse lymphocytic leukemia cell line L1210. We used three variants of L1210 cells: i) parental cells (S) negative for P-glycoprotein (P-gp) expression; ii) P-glycoprotein positive cells (R), obtained by selection with vincristine; iii) P-glycoprotein positive cells (T), obtained by stable transfection with a human gene encoding P-glycoprotein. We identified the most effective derivative 11 with a median lethal concentration of ≈13 µM in all three L1210 cell variants. The analysis of the apoptosis/necrosis induced by derivative 11 revealed that cell death was the result of apoptosis with late apoptosis characteristics. Derivative 11 did not induce a strong alteration in the proportion of cells in the G1, S or G2/M phase of the cell cycle, but a strong increase in the number of S, R and T cells in the subG1 phase was detected. These findings indicated that we identified the most effective inducer of cell death, derivative 11, and this derivative effectively induced cell death in S, R and T cells at similar inhibitory concentrations independent of P-gp expression.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Leucemia/metabolismo , Leucemia/patologia , Fenantrolinas/análise , Fenantrolinas/farmacologia , Quinolizinas/análise , Quinolizinas/farmacologia , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ativação Enzimática , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Fenantrolinas/química , Quinolizinas/química , Coloração e Rotulagem , Proteína X Associada a bcl-2/metabolismo
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 221: 117196, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31170603

RESUMO

A novel class of unexpected 1,10-phenanthrolinederivatives were synthesized from 2,3-dihydroacridin-4(1H)-ones with 3-aminonaphthalen-2-carboxylic acid in presence of phosphorus oxychloride at 130°C and simple perceptive emission intensity increasing assay was developed effectively to detect the very low concentrations of Zn2+ and Cd2+ ions. Emission intensity of compounds 3(a-c) directly related to the concentrations of Zn2+ and Cd2+ ions was due to metal chelating enhanced fluorescence (CHEF) effect and also its further validated by fluorescence lifetime measurement. Furthermore, the sensing mechanism for compounds 3(a-c) of Zn2+ and Cd2+ were sustained by theoretical calculations. Computational analysis results reveals that compounds 3(a-c) are more interested in Zn2+ ions than that of Cd2+ ions, while, compound 3c is more interested with Zn2+ and Cd2+ ions than those of the rest of the compounds. In addition, this proposed detection analysis has the direct application for monitoring Zn2+ and Cd2+ concentrations in tap and drinking water samples.


Assuntos
Cádmio/análise , Corantes Fluorescentes/química , Fenantrolinas/química , Zinco/análise , Calibragem , Corantes Fluorescentes/síntese química , Limite de Detecção , Espectroscopia de Ressonância Magnética , Modelos Químicos , Compostos de Fósforo/química , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
10.
Biometals ; 32(4): 671-682, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31230149

RESUMO

Hydrazide ligand, (Z)-N'-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)isonicotinohydrazide, 1 forms from a 1:1 Schiff base condensation reaction between isoniazid (INH) and 1,10-phenanthroline-5,6-dione (phendione). Ag+ and Mn2+ complexes with 1:2 metal:ligand stoichiometry are prepared: [Ag(1)2]NO3, [Ag(1)2]BF4 and [Mn(1)2](NO3)2. Polymeric {[Ag(1)(NO3)]}n has 1:1 stoichiometry and forms upon infusion of CH2Cl2 into a DMSO solution of [Ag(1)2]NO3. {[Ag(1)(NO3)]}n was structurally characterized using X-ray crystallography. Metal-free 1 and its 1:2 complexes exhibit very good, broad-spectrum antimicrobial activity and are not excessively toxic to mammalian cells (A549 lineage).


Assuntos
Anti-Infecciosos/química , Complexos de Coordenação/química , Isoniazida/química , Manganês/química , Fenantrolinas/química , Prata/química , Células A549 , Anti-Infecciosos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana
11.
Inorg Chem ; 58(14): 9452-9459, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31247836

RESUMO

The biexponential excited-state emission decay characteristic of DNA intercalated tris-bidentate dppz-based ruthenium complexes of the general form Ru(L)2dppz2+ has previously been explained by a binding model with two distinct geometry orientations of the bound ligands, with a distinct lifetime associated with each orientation. However, it has been found that upon DNA binding of Ru(phen)2dppz2+ the fractions of short and long lifetimes are strongly dependent on environmental factors such as salt concentration and, in particular, temperature. Analyzing isothermal titration calorimetry for competitive binding of Ru(phen)2dppz2+ enantiomers to poly(dAdT)2, we find that a consistent binding model must assume that the short and long lifetimes states of intercalated complexes are in equilibrium and that this equilibrium is altered when neighboring bound ligands affect each other. The degree of intercomplex binding is found to be a subtle manifestation of several attractive and repulsive factors that are highly likely to directly reflect the strong diastereomeric difference in the binding enthalpy and entropy values. In addition, as the titration progresses and the binding sites on the DNA lattice become increasingly occupied, a general resistance for the saturation of the binding sites is observed, suggesting diastereomeric crowding of the neighboring bound ligands.


Assuntos
Complexos de Coordenação/química , DNA/química , Substâncias Intercalantes/química , Modelos Moleculares , Estrutura Molecular , Fenantrolinas/química , Rutênio/química
12.
Eur J Med Chem ; 176: 492-512, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31132480

RESUMO

We report the design, synthesis and biological studies on a group of mixed ligand Fe(III) complexes as anti-cancer drug candidates, namely their interaction with DNA, cytotoxicity and mechanism(s) of action. The aim is to obtain stable, efficient and selective Fe-complexes to be used as anti-cancer agents with less damaging side effects than previously reported compounds. Five ternary Fe(III) complexes bearing a tripodal aminophenolate ligand L2-, H2L = N,N-bis(2-hydroxy-3,5-dimethylbenzyl)-N-(2-pyridylmethyl)amine, and different aromatic bases NN = 2,2'-bipyridine [Fe(L)(bipy)]PF6 (1), 1,10-phenanthroline [Fe(L)(phen)]PF6 (2), or a phenanthroline derivative co-ligand: [Fe(L)(amphen)]NO3 (3), [Fe(L)(amphen)]PF6 (3a), [Fe(L)(Clphen)]PF6 (4), [Fe(L)(epoxyphen)]PF6 (5) (where amphen = 1,10-phenanthroline-5-amine, epoxyphen = 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, Clphen = 5-chloro-1,10-phenanthroline) and the [Fe(L)(EtOH)]NO3 (6) complex are synthesized. The compounds are characterized in the solid state and in solution by elemental analysis, ESI-MS, magnetic susceptibility measurements and FTIR, UV-Vis, 1H and 13C NMR and fluorescence spectroscopies. [Fe(phen)Cl3] and [Fe(amphen)Cl3] were also prepared for comparison purposes. Spectroscopic binding studies indicate groove binding as the main interaction for most complexes with DNA, and for those containing amphen a B- to Z-DNA conformational change is proposed to occur. As determined via MTT analysis all compounds 1-6 are cytotoxic against a panel of three different cell lines (HeLa, H1299, MDA-MB-231). For selected compounds with promising cytotoxic activity, apoptosis was evaluated using cell and DNA morphology, TUNEL, Annexin V/7AAD staining and caspase3/7 activity. The compounds induce oxidative DNA damage on plasmid DNA and in cell culture as assessed by 8-oxo-Guanine and γH2AX staining. Comet assay confirmed the presence of genomic damage. There is also increased reactive oxygen species formation following drug treatment, which may be the relevant mechanism of action, thus differing from that normally assumed for cisplatin. The Fe(III)-complexes were also tested against strains of M. Tuberculosis (MTb), complex 2 depicting higher anti-MTb activity than several known second line drugs. Hence, these initial studies show prospective anti-cancer and anti-MTb activity granting promise for further studies.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ferro/química , Fenantrolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/farmacologia , Antituberculosos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , DNA/química , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Desenho de Fármacos , Estabilidade de Medicamentos , Humanos , Ligantes , Mycobacterium tuberculosis/efeitos dos fármacos , Fenantrolinas/síntese química , Fenantrolinas/química , Fenantrolinas/toxicidade , Estudos Prospectivos , Espécies Reativas de Oxigênio/metabolismo
13.
Mikrochim Acta ; 186(5): 325, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31049723

RESUMO

Protein p300 is a transcriptional co-activator that participates in many physiological processes including cell cycle control, differentiation and apoptosis. It serves (a) as a protein bridge that links specific transcription factors to the fundamental transcription machinery, (b) as a scaffold to complete multiple transcription cofactors, and (c) as an enzyme for acetylating histone and non-histone proteins. An ultrasensitive electrochemiluminescence (ECL) immunosensor is described here that is based on the use of a magnetic glassy carbon electrode modified with tetrahedral DNA with hollow structure, graphene oxide (GO) and gold nanocrystals. The use of a GO monolayer allows for greater carrying capacity and warrants a wider outer Helmholtz plane. Strong and stable ECL signals were achieved due to antigen-antibody interaction by using the ECL probe Ru(phen)32+. This immunosensor has a response that covers the 0.005 to 80 nM p300 concentration range and has a 1 pM detection limit. It was exploited for the determination of p300 in HeLa cell lysate and (spiked) serum. Graphical abstract Schematic presentation of an ultrasensitive Faraday-cage electrochemiluminescence immunosensor toward the transcriptional co-activator p300 analysis is presented based on a graphene oxide monolayer and tetrahedral DNA-mediated signal amplification.


Assuntos
Proteína p300 Associada a E1A/análise , Ouro/química , Grafite/química , Nanopartículas Metálicas/química , Nanocompostos/química , Técnicas Biossensoriais/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Eletrodos , Corantes Fluorescentes/química , Células HeLa , Humanos , Imunoensaio/métodos , Limite de Detecção , Medições Luminescentes/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Compostos Organometálicos/química , Fenantrolinas/química
14.
Chem Commun (Camb) ; 55(60): 8764-8767, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31139806

RESUMO

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


Assuntos
DNA/química , Substâncias Intercalantes/química , Compostos Organometálicos/química , Fenantrenos/química , Adutos de DNA/síntese química , Guanina/química , Substâncias Intercalantes/efeitos da radiação , Ligantes , Luz , Conformação de Ácido Nucleico , Compostos Organometálicos/efeitos da radiação , Fenantrenos/efeitos da radiação , Fenantrolinas/química , Fenantrolinas/efeitos da radiação , Rutênio/química
15.
Colloids Surf B Biointerfaces ; 180: 289-297, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31071568

RESUMO

A new strategy to encapsulating the drug curcumin into the hydrophobic core of the iron-phenanthroline nanocomplex (NIP) and eventually its release is signified. NIP was prepared via coordinate interaction between Fe2+ and the lone pairs present on the N atoms of the bidentate phenanthroline ligand (spherical morphology, diameter 18.8 nm, mesoporous with pore size 2.443 nm, amorphous). Thereafter, curcumin was successfully encapsulated (NCIP) in NIP, resulting in its enhanced stability (spherical morphology, diameter 46.8 nm). The nanocomplex NIP was used for drug delivery applications. We evaluated the anti-HIV effects of NCIP in vitro on cultures of HIV infected human microglia. The treatment of HIV-1 infected microglia with NCIP significantly decreased the expression of HIV-p24 by 41% and pro-inflammatory mediators TNF-α, IL-8 and NO by 61.2%, 41% and 50.2%, respectively, compared to NIP. Flow cytometry data also support the decrease in TNF-α and IL-8 expression in case of NCIP. NCIP induced antioxidative effects by increasing the gene expression of catalase (CAT) and simulatenously decreasing hemeoxygenase-1 (HMOX-1) gene expression, thereby maintaining homeostasis which reduces neuroinflammation. These results support our premise that NCIP may be a significant adjuvant when used with traditional anti-retroviral regimens and may ameliorate HIV-1 associated neurotoxicity.


Assuntos
Fármacos Anti-HIV/farmacologia , Curcumina/farmacologia , Composição de Medicamentos , Ferro/química , Nanopartículas/química , Fenantrolinas/química , Adsorção , Biomarcadores/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Microglia/citologia , Microglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Porosidade , Temperatura
16.
Artigo em Inglês | MEDLINE | ID: mdl-31081456

RESUMO

Three new Ru(II) polypyridyl complexes [Ru(phen)2CIIP]2+ (1) {CIIP = 2-(5-Chloro-3a H-Isoindol-3-yl)-1H-Imidazo[4,5-f][1, 10]phenantholine} (phen = 1, 10 phenanthroline), [Ru(bpy)2CIIP]2+ (2) (bpy = 2, 2' bipyridine) and [Ru(dmb)2CIIP]2+ (3) (dmb = 4, 4'-dimethyl 2, 2' bipyridine) were synthesized and characterized by different spectral methods. The DNA-binding behavior of these complexes was investigated by absorption, emission spectroscopic titration and viscosity measurements, indicating that these three complexes bind to CT-DNA in an intercalative mode, but binding affinities of these complexes were different. The DNA-binding constants Kb of complexes 1, 2 and 3 were calculated in the order of 106. All three complexes cleave pBR322 DNA in photoactivated cleavage studies and exhibit good antimicrobial activity. Anticancer activity of these Ru(II) complexes was evaluated in MCF7 cells. Cytotoxicity by MTT assay showed growth inhibition in a dose dependent manner. Cell cycle analysis by flow cytometry data showed an increase in Sub G1 population. Annexin V FITC/PI staining confirms that these complexes cause cell death by the induction of apoptosis.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Complexos de Coordenação/química , Substâncias Intercalantes/química , Isoindóis/química , Fenantrolinas/química , Piridinas/química , Rutênio/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , DNA/metabolismo , Clivagem do DNA , Escherichia coli/efeitos dos fármacos , Humanos , Substâncias Intercalantes/farmacologia , Isoindóis/farmacologia , Células MCF-7 , Fenantrolinas/farmacologia , Processos Fotoquímicos , Piridinas/farmacologia , Termodinâmica
17.
Anticancer Res ; 39(4): 1859-1867, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30952726

RESUMO

BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS: 1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 µM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Neoplasias da Mama/metabolismo , Portadores de Fármacos , Endocitose , Mucina-1/metabolismo , Fenantrolinas/metabolismo , Radiossensibilizantes/metabolismo , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Viabilidade , Feminino , Compostos Ferrosos/química , Humanos , Células MCF-7 , Mucina-1/genética , Fenantrolinas/química , Fenantrolinas/farmacologia , Radiossensibilizantes/farmacologia
18.
Dalton Trans ; 48(24): 8578-8593, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30946409

RESUMO

Immunocompromised cancer patients are often at high risk of developing infections. Standard infection control measures are required to prevent the onset of infection but, under some circumstances, antimicrobial prophylaxis is necessary. We have developed a family of innovative metallo-antibiotics of general formula [Cu(N,N)(CipA)Cl] where N,N represents a phenanthrene ligand and CipA stands for a derivative of the clinically used fluoroquinolone antibiotic ciprofloxacin. The X-ray crystal structure of one member from this family, [Cu(phen)(CipA)Cl] (where phen is 1,10-phenanthroline), is also reported. These complexes combine into one drug entity a Cu-N,N-framework with DNA binding and DNA oxidant properties and an antibiotic derivative with known anti-proliferative and anti-microbial activities. The complexes were all found to exhibit excellent DNA recognition with binding affinity of lead agents in the order of ∼107 M(bp)-1. Biophysical studies involving calf thymus DNA indicate the complexes intercalate or semi-intercalate DNA via the minor groove. All complexes exhibited excellent nuclease activity with DNA strand scission being mediated predominantly via superoxide and hydroxyl radicals. The complexes were found to have promising anti-proliferative effects against a human breast adenocarcinoma cell line (MCF-7) and a human prostate carcinoma cell line (DU145) with low micromolar and, in some cases, nanomolar cytotoxicities observed. Selective targeting of Gram positive bacteria was also identified by this complex class with one lead compound having an order of magnitude greater potency against Methicillin-resistant S. aureus (MRSA) as compared to the CipA ligand. Importantly, from a clinical stand point, these complexes were also found to be well tolerated in an in vivo Galleria mellonella larvae model, which has both functional and structural similarities to that of the innate immune system of mammals.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Ciprofloxacino/química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Antibacterianos/metabolismo , Antineoplásicos/metabolismo , Cobre/química , DNA/metabolismo , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Humanos , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/metabolismo , Fenantrolinas/química
19.
Artigo em Inglês | MEDLINE | ID: mdl-30942140

RESUMO

A new copper(II) complex, [Cu(pse)(phen)Cl2]; in which phen = 1,10-phenanthroline and pse = pseudoephedrine hydrochloride drug; was synthesized and characterized by FT-IR, Mass and UV-Vis spectroscopy in combination with computational methods. Binding interaction of this complex with calf thymus DNA (ct-DNA) has been investigated by absorption, emission, circular dichroism, molecular docking and viscosity measurements. The complex displays significant binding properties of ct-DNA. The results of fluorescence and UV-Vis absorption spectroscopy indicated that, this complex interacted with ct-DNA in a groove-binding mode, and the binding constant was 8 × 104 L mol-1. Competitive fluorimetric studies with Hoechst 33258 have shown that Cu(II) complex exhibit the ability to displace the DNA-bound Hoechst 33258 indicating that it binds to DNA in strong competition with Hoechst 33258 for the groove binding. Furthermore, the complex induces detectable changes in the CD spectrum of ct-DNA and does not induce any changes in DNA viscosity which verified the groove-binding mode. The molecular modeling results illustrated that the complex strongly binds to groove of DNA by relative binding energy of docked structure (-27.61 kJ mol-1).


Assuntos
Complexos de Coordenação/química , Cobre/química , DNA/química , Fenantrolinas/química , Pseudoefedrina/química , Substâncias Intercalantes/química , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Termodinâmica , Viscosidade
20.
Dalton Trans ; 48(18): 6132-6152, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30990506

RESUMO

A ligand skeleton combining a 1,10-phenanthroline (phen) binding site and one or two heptadentate N3O4 aminocarboxylate binding sites, connected via alkyne spacers to the phen C3 or C3/C8 positions, has been used to prepare a range of heteronuclear Ru·M and Ru·M2 complexes which have been evaluated for their cell imaging, relaxivity, and photophysical properties. In all cases the phen unit is bound to a {Ru(bipy)2}2+ unit to give a phosphorescent {Ru(bipy)2(phen)}2+ luminophore, and the pendant aminocarboxylate sites are occupied by a secondary metal ion M which is either a lanthanide [Gd(iii), Nd(iii), Yb(iii)] or another d-block ion [Zn(ii), Mn(ii)]. When M = Gd(iii) or Mn(ii) these ions provide the complexes with a high relaxivity for water; in the case of Ru·Gd and Ru·Gd2 the combination of high water relaxivity and 3MLCT phosphorescence from the Ru(ii) unit provides the possibility of two different types of imaging modality in a single molecular probe. In the case of Ru·Mn and Ru·Mn2 the Ru(ii)-based phosphorescence is substantially reduced compared to the control complexes Ru·Zn and Ru·Zn2 due to the quenching effect of the Mn(ii) centres. Ultrafast transient absorption spectroscopy studies on Ru·Mn (and Ru·Zn as a non-quenched control) reveal the occurrence of fast (<1 ns) PET in Ru·Mn, from the Mn(ii) ion to the Ru(ii)-based 3MLCT state, i.e. MnII-(phen˙-)-RuIII → MnIII-(phen˙-)-RuII; the resulting MnIII-(phen˙-) state decays with τ ≈ 5 ns and is non-luminescent. This occurs in conformers when an ET pathway is facilitated by a planar, conjugated bridging ligand conformation connecting the two units across the alkyne bridge but does not occur in conformers where the two units are electronically decoupled by a twisted conformation of the bridging ligand. Computational studies (DFT) on Ru·Mn confirmed both the occurrence of the PET quenching pathway and its dependence on molecular conformation. In the complexes Ru·Ln and Ru·Ln2 (Ln = Nd, Yb), sensitised near-infrared luminescence from Nd(iii) or Yb(iii) is observed following photoinduced energy-transfer from the Ru(ii) core, with Ru → Nd energy-transfer being faster than Ru → Yb energy-transfer due to the higher density of energy-accepting states on Nd(iii).


Assuntos
Aminas/química , Ácidos Carboxílicos/química , Complexos de Coordenação/química , Metais/química , Fenantrolinas/química , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , Transferência de Energia , Corantes Fluorescentes/química , Células HeLa , Humanos , Cinética , Ligantes , Modelos Moleculares , Estrutura Molecular , Imagem Óptica/métodos , Processos Fotoquímicos , Espectrometria de Fluorescência/métodos , Relação Estrutura-Atividade
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