Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 474
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chem Commun (Camb) ; 56(10): 1464-1480, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31967621

RESUMO

This review discusses the advantages of using luminescent d6-transition-metal complexes as cell probes for optical microscopy. In particular it focusses on the Thomas group's use of specific complexes as "building blocks" toward the construction of biomolecular binding substrates, with DNA being a particular target. Using this approach, a range of new imaging probes for conventional optical microscopy, nanoscopy and transmission electron microscopy have been identified. Through selection of specific metal centres and by substitution of coordinated ligands we illustrate how new chemotherapeutics, photo-therapeutics, and theranostics have been identified and developed from the original architectures.


Assuntos
Complexos de Coordenação/química , DNA/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Apoptose/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Meios de Contraste/química , Meios de Contraste/metabolismo , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , DNA/metabolismo , Humanos , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Nanomedicina Teranóstica
2.
Chemosphere ; 240: 124942, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31574434

RESUMO

Advanced oxidation processes (AOPs) can degrade heavy metal complexes in wastewater to improve the removal efficiency of metals. However, the influences of AOP treatments on toxicity induced by metal complexes are not well understood. This study compared the toxicity induced by EDTA-copper (Cu) after UV/persulfate (PS) and UV/H2O2 treatments on luminescent bacteria and human HepG2 cells. The results showed that EDTA-Cu complexes decreased Cu toxicity in luminescent bacteria but increased the cytotoxicity in HepG2 cells, indicating species-specific toxicity. The UV/PS and UV/H2O2 treatments under most pH values and [oxidant]/[EDTA-Cu] conditions decreased the toxicity of EDTA-Cu in HepG2 cells but increased the toxicity in luminescent bacteria. When the ratio of [oxidant] to [EDTA-Cu] was 10, low toxicity in treated solutions was observed in both UV treatment processes. The alkaline precipitation treatment had a significant influence on toxicity reduction after UV/PS treatment; however, it had minimal influence on the UV/H2O2 treatment system. The Cu and total organic carbon (TOC) removal efficiency cannot completely explain the results of toxicity assays. EDTA-Cu intermediates might play important roles in changing the toxicity of EDTA-Cu after both UV treatments. This study provides insights into evaluating the treatment efficiency of UV/PS and UV/H2O2 on EDTA-Cu decomplexation.


Assuntos
Complexos de Coordenação/toxicidade , Cobre/toxicidade , Ácido Edético/toxicidade , Peróxido de Hidrogênio/química , Photobacterium/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Transportadores de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Ácido Edético/química , Células Hep G2 , Humanos , Oxirredução , Raios Ultravioleta , Águas Residuárias/química
3.
Chem Commun (Camb) ; 56(5): 762-765, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31845680

RESUMO

A multifunctional photodynamic therapy (PDT) nanoplatform, characterized by red-shifted absorption and emission, was fabricated using an UiO-66-based metal-organic framework (MOF), a biscyclometalated iridium(iii) complex, and a pH/ROS-responsive polycationic polymer. Noticeably, this promising nanoplatform exhibited good biocompatibility in the dark and produced abundant ROS upon light irradiation, which could achieve apparent endo/lysosome escape and kill cancer cells effectively.


Assuntos
Resinas Acrílicas/farmacologia , Complexos de Coordenação/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Resinas Acrílicas/química , Resinas Acrílicas/toxicidade , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Desenho de Drogas , Células HeLa , Humanos , Irídio/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/toxicidade , Microscopia de Fluorescência/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/toxicidade , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Compostos de Amônio Quaternário/toxicidade , Espécies Reativas de Oxigênio/metabolismo
4.
Ecotoxicol Environ Saf ; 183: 109484, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398583

RESUMO

This work evaluated the degradation of the Acid Blue 161 and Procion Red MX-5B dyes in a binary solution by the filamentous fungus Aspergillus terreus and the yeast Saccharomyces cerevisiae in systems with and without electrochemical oxidation as the pretreatment process. UV-Vis spectrophotometry, high-performance liquid chromatography with (HPLC), Fourier transform infrared (FT-IR) spectroscopy and Salmonella/microsome assay (Ames test) were applied towards the degradation analysis of the dyes. Adsorption tests with white clay immobilized on alginate were also conducted after the discoloration treatments to remove intermediate metabolites formed during the degradation of the dye molecules. The discoloration treatments led to the complete color removal of the solutions in all the systems tested. The clay demonstrated affinity for the metabolites formed after discoloration treatments, the removal rates were variable, but the all systems has proved efficient. The Salmonella/microsome assay (Ames test) with strains TA98 and TA100 in the absence and presence of exogenous metabolism (S9 microsomal system, Moltox) revealed that the initial molecules and by-products of the metabolism of the dyes were direct mutagens. The electrochemical/A. terreus/clay system was able to discolor the solutions and transform the direct mutagens into non-mutagenic compounds in addition to reducing the mutagenic potency of the pro-mutagens to the Salmonella strain TA100/S9, which demonstrates the high efficiency of this system with regard to discoloring and degrading azo dye molecules and their by-products. Therefore, this study showed that although not having standard treatment system for this type of pollutant, the combination of treatments can be considered promising. The use of electrochemical oxidation along with microbiological treatment may lead to the degradation and mineralization of these compounds, reducing or eliminating the environmental impact caused by the improper disposal of these dyes in aquatic environments.


Assuntos
Compostos Azo/metabolismo , Compostos Azo/toxicidade , Corantes/metabolismo , Corantes/toxicidade , Mutagênicos/metabolismo , Mutagênicos/toxicidade , Aspergillus/metabolismo , Cromatografia Líquida de Alta Pressão , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , Naftalenossulfonatos/metabolismo , Naftalenossulfonatos/toxicidade , Oxirredução , Estresse Oxidativo , Saccharomyces cerevisiae/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Dalton Trans ; 48(35): 13396-13405, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432885

RESUMO

In this study, five ruthenium arene complexes with fluorene-bearing N,N-(1) and N,O-(2) donor Schiff base ligands were synthesized and fully characterized. Cationic ruthenium complexes 3[X], ([Ru(η6-C6H6)(Cl)(fluorene-N[double bond, length as m-dash]CH-pyridine)][X] (where X = BF4, PF6, BPh4), were obtained by reacting ligand 1 with [Ru(η6-C6H6)Cl2]2 in the presence of NH4X salts, whereas neutral complex 4, Ru(η6-C6H6)(Cl)(fluorene-N[double bond, length as m-dash]CH-naphtholate), was isolated by reacting ligand 2 with the same precursor. It was possible to obtain a cationic version of the latter, 5[BF4], by reacting 4 with AgBF4 in the presence of pyridine. All compounds were fully characterized by NMR and HR-ESI-MS whereas some of them were also analyzed by single crystal X-ray analysis. Their in vitro antiproliferative activity was also assessed in human breast cancer cell lines, notably MCF-7 and T47D. Complex 4 and its cationic counterpart 5[BF4] were found to be the most cytotoxic compounds of the series (IC50 = 6.2-16.2 µM) and displayed higher antiproliferative activities than cisplatin in both cell lines. It was found that 5[BF4] undergoes a ligand exchange reaction and readily converts to 4 in the presence of 0.1 M NaCl, explaining the similarity in their observed cytotoxicities. Whereas 3[BF4] and 3[PF6] were found inactive at the tested concentrations, 3[BPh4] displayed a considerable cytotoxicity (IC50 = 16.7-27.8 µM). Notably, 3[BPh4], 4 (and 5[BF4]) were active against T47D, a cisplatin resistant cell line. Interestingly, 4 (16.4 µM) was found to be less cytotoxic than 3[BPh4] and cisplatin (6.6 and 7.9 µM, respectively) in breast healthy cells (MCF-12A). However, in comparison to 4 and cisplatin (at 10 µM), a lower in vivo toxicity was observed for complex 3[BPh4] on the development of zebrafish (Danio rerio) embryos.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Fluorenos/química , Rutênio/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular , Peixe-Zebra/embriologia
6.
Dalton Trans ; 48(41): 15613-15624, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31408065

RESUMO

The synthesis, structural and photophysical characterisation of four tricarbonyl rhenium(i) complexes bound to 1,10-phenanthroline and a tetrazolato ancillary ligand are reported. The complexes are differentiated by the nature (hydroxy or methoxy) and position (meta or para) of the substituent attached to the phenyl ring in conjugation to the tetrazole ring. The complexes exhibit phosphorescence emission from triplet charge transfer excited states, with the maxima around 600 nm, excited state lifetime decays in the 200-300 ns range, and quantum yield values of 4-6% in degassed acetonitrile solutions. The nature and position of the substituent does not significantly affect the photophysical properties, which remain unchanged even after deprotonation of the hydroxide group on the phenol ring. The interpretation of the photophysical data was further validated by resonance Raman spectroscopy and time-dependent density functional theory calculations. All the complexes are internalised within cells, albeit to variable degrees. As highlighted by a combination of flow cytometry and confocal microscopy, the species display diffuse cytoplasmic localisation except for the complex with the hydroxy functional group at the para position, which reveals lower accumulation in cells and more pronounced punctate staining. Overall, the complexes displayed low levels of cytotoxicity.


Assuntos
Complexos de Coordenação/química , Fenol/química , Rênio/química , Tetrazóis/química , Animais , Complexos de Coordenação/toxicidade , Ligantes , Camundongos , Modelos Moleculares , Conformação Molecular , Prótons , Teoria Quântica , Células RAW 264.7
7.
Chem Commun (Camb) ; 55(54): 7852-7855, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31215553
8.
Chem Commun (Camb) ; 55(60): 8860-8863, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31219109

RESUMO

We report the first dual-responsive 19F MRI and fluorescence imaging probe for cellular hypoxia. The Cu2+-based probe exhibits no 19F MR signal and reduced fluorescence signal due to paramagnetic quenching; however, the probe turns-on in both modes following reduction to Cu+. This bimodal agent can differentiate hypoxic and normoxic cells in both modalities.


Assuntos
Hipóxia Celular/fisiologia , Complexos de Coordenação/química , Fluoresceínas/química , Corantes Fluorescentes/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Cobre/química , Fluoresceínas/síntese química , Fluoresceínas/toxicidade , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Flúor , Imagem por Ressonância Magnética de Flúor-19/métodos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Microscopia de Fluorescência/métodos
9.
Inorg Chem ; 58(13): 8800-8819, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247881

RESUMO

Very few inorganic antineoplastic drugs have entered the clinic in the last decades, mainly because of toxicity issues. Because copper is an essential trace element of ubiquitous occurrence, decreased side effects could be expected in comparison with the widely used platinum anticancer compounds. In the present work, two novel hydrazonic binucleating ligands and their µ-hydroxo dicopper(II) complexes were prepared and fully characterized. They differ by the nature of the aromatic group present in their aroylhydrazone moieties: while H3L1 and its complex, 1, possess a thiophene ring, H3L2 and 2 contain the more polar furan heterocycle. X-ray diffraction indicates that both coordination compounds are very similar in structural terms and generate dimeric arrangements in the solid state. Positive-ion electrospray ionization mass spectrometry analyses confirmed that the main species present in a 10% dimethyl sulfoxide (DMSO)/water solution should be [Cu2(HL)(OH)]+ and the DMSO-substituted derivative [Cu2(L)(DMSO)]+. Scattering techniques [dynamic light scattering (DLS) and small-angle X-ray scattering] suggest that the complexes and their free ligands interact with bovine serum albumin (BSA) in a reversible manner. The binding constants to BSA were determined for the complexes through fluorescence spectroscopy. Moreover, to gain insight into the mechanism of action of the compounds, calf thymus DNA binding studies by UV-visible and DLS measurements using plasmid pBR322 DNA were also performed. For the complexes, DLS data seem to point to the occurrence of DNA cleavage to Form III (linear). Both ligands and their dicopper(II) complexes display potent antiproliferative activity in a panel of four cancer cell lines, occasionally even in the submicromolar range, with the complexes being more potent than the free ligands. Our data on cellular models correlate quite well with the DNA interaction experiments. The results presented herein show that aroylhydrazone-derived binucleating ligands, as well as their dinuclear µ-hydroxodicopper(II) complexes, may represent a promising structural starting point for the development of a new generation of highly active potential antitumor agents.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Hidrazonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Bovinos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Cobre/química , DNA/química , Clivagem do DNA/efeitos dos fármacos , Cães , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/toxicidade , Isomerismo , Ligantes , Células Madin Darby de Rim Canino , Camundongos , Plasmídeos/química , Multimerização Proteica/efeitos dos fármacos , Soroalbumina Bovina/metabolismo
10.
Eur J Med Chem ; 177: 350-361, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158749

RESUMO

The relationship between chemical structure and in vitro cytotoxic activities of a series of azastibocine-framework organoantimony(III) halide complexes against cancerous (HepG2, MDA-MB-231, MCF-7 and HeLa) and nonmalignant (HEK-293) cell lines was studied for the first time. A positive correlation between cytotoxic activity and the length of N→Sb coordinate bond on azastibocine framework of same nitrogen substituent was observed. By comparison, the organoantimony(III) complex 6-cyclohexyl-12-fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (C4) exhibited the highest selectivity index, giving a IC50(nonmalignant)/IC50(cancerous) ratio of up to 8.33. The results of cell cycle analysis indicated that the inhibitory effect of C4 on the cellular viability was caused by cell cycle arrest mainly at the S phase. The necrosis induced by C4 was confirmed by the Trypan blue dye exclusion test and the increase of lactic dehydrogenase (LDH) released in the culture medium. Furthermore, evaluation of the levels of intracellular reactive oxygen species (ROS) in MDA-MB-231 cells, by quantifying the relative fluorescence units (RFU) using spectrofluorometer, indicated that cytotoxic activity of C4 is dependent on the production of ROS. This work established the correlation between cytotoxic activity and N→Sb inter-coordination, a finding that provided theoretical and experimental basis for in-depth design of antimony-based organometallic complexes as potential anticancer agents.


Assuntos
Antimônio/química , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , L-Lactato Desidrogenase/metabolismo , Estrutura Molecular , Necrose/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Relação Estrutura-Atividade
11.
Eur J Med Chem ; 174: 216-225, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31042617

RESUMO

The identification of a valid therapeutic treatment for Alzheimer's disease (AD) represents nowadays an urgent and still unmet medical need, since currently available anti-AD drugs only relieve symptoms and show a modest efficacy. Recent evidence indicates that multi-target-directed ligands (MTDLs) can potentially provide an effective strategy to develop innovative therapies directed towards the onset and progression of this multifactorial neurodegenerative disorder. In this work we designed, synthesized and evaluated a new series of MTDLs bearing the rivastigmine skeleton (ChE-inhibitor) linked to known metal-chelating moieties with linkers of different length. For all the novel derivatives, AChE/BuChE inhibitory activity, ROS scavenging activity and potential cytotoxicity have been assessed. For the best compound (4), copper chelating properties and neuroprotective effects were also evaluated. Our data demonstrated that hybrid derivative 4 is able to effectively inhibit AChE and BuChE and to chelate copper, showing a protective action on neurons. These results, although preliminary, indicate that compound 4 can be considered as a possible hit molecule for the development of new anti-AD MTDLs.


Assuntos
Quelantes/farmacologia , Complexos de Coordenação/farmacologia , Cobre/química , Fármacos Neuroprotetores/farmacologia , Rivastigmina/análogos & derivados , Rivastigmina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Butirilcolinesterase/metabolismo , Linhagem Celular Transformada , Quelantes/síntese química , Quelantes/toxicidade , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/toxicidade , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Camundongos , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/toxicidade , Rivastigmina/síntese química , Rivastigmina/toxicidade
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 Drogas , 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.
Chem Biol Interact ; 307: 147-153, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31071334

RESUMO

The development of novel agrochemical compounds to reduce the use of pesticides with high ecological impact is urgently needed. A complex of Mg with two flavonoids hesperidin and phenanthroline [Mg(hesp)2(phen)], referred to as MgHP, results in high insecticidal activity against urban, agricultural and forest insect pests. In vitro cytotoxicity biomarkers were used to assess the mechanism of action MgHP on fish cells, as this insecticide can reach the aquatic environment and affect its biota. The cytotoxic effects of MgHP were evaluated at different concentrations (0, 0.1, 1, 10, 100 and 1000 ng mL-1) in a zebrafish hepatocyte cell line (ZF-L). Twenty-four hours of exposure to high concentrations (10 and 1000 ng mL-1) of MgHP affected cell confluence and morphology. Mitochondrial activity and lysosomal retention ability decreased as the MgHP concentration was increased. Cell membrane injury, apoptosis, and necrosis were not induced. These results suggested that toxicity to ZF-L cells was due loss of organellar activity caused by MgHP, which may also include activation of an alternative cell death mechanism. However, after 96 h of exposure, the toxic effects of MgHP may be mitigated, even at high concentrations, enabling cellular population recovery. These data provide important information on the mechanism of action of MgHP on hepatocyte fish cells and stimulate analyses to elucidate the cellular responses to MgHP.


Assuntos
Complexos de Coordenação/toxicidade , Inseticidas/toxicidade , Lisossomos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Inseticidas/química , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
14.
Artif Cells Nanomed Biotechnol ; 47(1): 1746-1757, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31062618

RESUMO

To evaluate the safety and efficacy of novel cobalt complex with sulindac (Co-SLD), the zebrafish and oral squamous cell carcinoma CAL27 were investigated in the present study. The developmental toxicity of Co-SLD ranging from 5 to 20 µM was determined by exposure to 3-144-h post-fertilization (hpf) zebrafish. Our data showed that Co-SLD did not cause to the appreciable toxicity at low concentration (5 and 10 µM). A remarkable toxicity was observed at high concentration (20 µM), including increased mortality and malformation, delayed hatchability, reduced heart rate as well as suppressed behaviour. With regard to the antitumor activity of Co-SLD, inhibited cell growth and migration capability were outstandingly observed in oral squamous cell carcinoma treated with 10 and 20 µM Co-SLD, which could be mainly attributed to the Co-SLD-elicited mitochondrial damage as marked by the depression of mitochondrial membrane potential, ROS accumulation and ATP depletion. Furthermore, administration of 10 µM Co-SLD was an optimal concentration not only to avoid the normal tissue toxicity, but also to enhance the killing of cancer cells via disrupting mitochondrial dysfunction. Taken together the above results demonstrated the desirable response of oral squamous cell carcinoma to Co-SLD.


Assuntos
Carcinoma de Células Escamosas/patologia , Cobalto/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias Bucais/patologia , Sulindaco/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/toxicidade , Relação Dose-Resposta a Droga , Humanos , Locomoção/efeitos dos fármacos , Mitocôndrias/patologia , Peixe-Zebra
15.
Inorg Chem ; 58(13): 8587-8595, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31117633

RESUMO

A new N,O-based BODIPY ligand was synthesized and further utilized to develop highly fluorescent and photostable Ru(II), Rh(III), and Ir(III) metal complexes. The complexes were fully characterized by different analytical techniques including single-crystal XRD studies. The photostabilities and live cell imaging capabilities of the complexes were investigated via confocal microscopy. The complexes localized specifically in the mitochondria of live cells and showed negligible cytotoxicities at a concentration used for imaging purposes. They also exhibited high photostabilities, with fluorescence intensities remaining above 50% after 1800 scans.


Assuntos
Compostos de Boro/metabolismo , Complexos de Coordenação/metabolismo , Corantes Fluorescentes/metabolismo , Mitocôndrias/metabolismo , Transporte Biológico , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Compostos de Boro/toxicidade , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Complexos de Coordenação/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Irídio/química , Ligantes , Microscopia Confocal , Fotodegradação , Ródio/química , Rutênio/química
16.
Int J Biol Macromol ; 132: 801-810, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30953722

RESUMO

Iron is essential in fundamental bioactivities, so it makes sense to improve the efficiency of iron on epithelial transport. In this work, a novel polysaccharide­iron(III) complex (FVP-Fe(III)) was prepared from Flammulina velutipes with a specific structure. The FVP-Fe(III) had a molecular weight of 15.13 kDa with a monosaccharide composition of mannose, galacturonic acid, glucose, galactose, xylose, fucose in a molar ratio 3.6:2.1:60.8:18.7:3.9:10.9. In the vitro digestion model, the complex could maintain better solubility and steady of iron than FeSO4. In the cell assay, FVP-Fe(III) showed lower cytotoxicity and better absorption. The transport amount of FVP-Fe(III) was 1.5-fold of FeSO4 at same concentration and 1.8-fold of FeSO4 at same time. The transport was mediated by the peptide transporter (pepT1) active transport pathway and the efflux of the sample was mainly mediated by multidrug-resistance proteins (MRP) transporter. The results of this study suggested that the polysaccharide obtained from F. velutipes could be developed a new kind of iron delivery for further study.


Assuntos
Absorção Fisico-Química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Flammulina/química , Ferro/química , Polissacarídeos/química , Transporte Biológico , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/toxicidade , Digestão , Epitélio/metabolismo , Humanos , Intestinos/fisiologia , Estômago/fisiologia
17.
ACS Appl Mater Interfaces ; 11(17): 15417-15425, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964627

RESUMO

The iridium(III)-cyanine complex (IrCy) was fabricated by conjugating an iridium(III) complex to a cyanine dye with an intense near-infrared (NIR) absorption. IrCy complex nanoparticles (NPs) with high water solubility and photostability were prepared by a solvent evaporation-induced self-assembly strategy. Considering their effective photacoustic (PA) imaging and generation of 1O2 property with 808 nm laser irradiation in aqueous solution, PA imaging guided NIR-driven photodynamic therapy in vivo was effectively conducted in the 4T1 xenograft model. We developed a real-time PA imaging methodology to investigate the pharmacokinetics, tumor targeting, and biodistribution of IrCy NPs. Taking advantage of the analysis of the PA signal of the common iliac vein, the blood circulation half-life of IrCy NPs in mice was calculated to be ∼18 h, and the enhanced permeability and retention effect of IrCy NPs offered the maximum targeting property in the tumor at about 24 h. The obvious change of PA imaging signal in kidney and bladder confirmed IrCy NPs should be excreted partially from the urine system, and the PA signal decreased from 12.5× to 2.8× in the liver, and from 28.8× to 9.4× in the spleen also confirmed the hepatic metabolic pathway.


Assuntos
Carbocianinas/química , Complexos de Coordenação/química , Irídio/química , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , Meia-Vida , Humanos , Lasers , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imagem Óptica/métodos , Técnicas Fotoacústicas , Fotoquimioterapia , Oxigênio Singlete/metabolismo , Distribuição Tecidual , Transplante Heterólogo
18.
Chemistry ; 25(35): 8353-8362, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-30939221

RESUMO

Accurate diagnosis of tumor characteristics, including its location and boundary, is of immense value to subsequent therapy. Activatable magnetic resonance imaging (MRI) contrast agents that respond to tumor-specific microenvironments, such as the redox state, pH, and enzyme activity, enable better mapping of tumor tissue. However, the practical application of most reported activatable agents is hampered by problems including potential toxicity, inefficient elimination, and slow activation. In this study, we developed a zwitterionic iron complex (Fe-ZDS) as a positive MRI contrast agent for tumor-specific imaging. Fe-ZDS could dissociate in weakly acidic solution rapidly, accompanied by clear longitudinal relaxivity (r1 ) enhancement, which enabled the complex to act as a pH-sensitive contrast agent for tumor-specific MR imaging. In vivo experiments showed that Fe-ZDS rapidly enhanced the tumor-to-normal contrast ratio by >40 %, which assisted in distinguishing the tumor boundary. Furthermore, Fe-ZDS circulated freely in the bloodstream and was excreted relatively safely via kidneys owing to its zwitterionic nature. Therefore, Fe-ZDS is an ideal candidate for a tumor-specific MRI contrast agent and holds considerable potential for clinical translation.


Assuntos
Materiais Biocompatíveis/química , Complexos de Coordenação/química , Neoplasias/diagnóstico por imagem , Animais , Materiais Biocompatíveis/farmacocinética , Materiais Biocompatíveis/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular , Complexos de Coordenação/farmacocinética , Complexos de Coordenação/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Ferro/química , Rim/efeitos dos fármacos , Imagem por Ressonância Magnética/métodos , Camundongos Endogâmicos BALB C , Distribuição Tecidual , Microambiente Tumoral
19.
Chemistry ; 25(38): 8970-8974, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-30901122

RESUMO

This communication reports novel luminescent rhenium(I)-polypyridine complexes appended with a perylene diimide (PDI) or benzoperylene monoimide (BPMI) moiety through a non-conjugated linker. The photophysical and photochemical properties originating from the interactions of the metal polypyridine and perylene units were exploited to afford new cellular reagents with thiol-sensing capability and excellent photocytotoxic activity.


Assuntos
Complexos de Coordenação/química , Substâncias Luminescentes/química , Perileno/análogos & derivados , Piridinas/química , Rênio/química , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/toxicidade , Transferência Ressonante de Energia de Fluorescência , Células HeLa , Humanos , Substâncias Luminescentes/toxicidade , Microscopia Confocal , Imagem Óptica , Piridinas/toxicidade , Rênio/toxicidade , Compostos de Sulfidrila/análise
20.
Dalton Trans ; 48(18): 6026-6039, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30724926

RESUMO

In this paper, four new ruthenium complexes, [Ru(N-S)(dppm)2]PF6 (1), [Ru(N-S)(dppe)2]PF6 (2), [Ru(N-S)2(dppp)] (3) and [Ru(N-S)2(PPh3)2] (4) [dppm = 1,1-bis(diphenylphosphino)methane, dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, PPh3 = triphenylphosphine and N-S = 2-mercaptopyrimidine anion] were synthesized and characterized using spectroscopy techniques, molar conductance, elemental analysis, electrochemical techniques and X-ray diffraction. The DNA binding studies were investigated using voltammetry and spectroscopy techniques. The results show that all complexes exhibit a weak interaction with DNA. HSA interaction with the complexes was studied using fluorescence emission spectroscopy, where the results indicate a spontaneous interaction between the species by a static quenching mechanism. The cytotoxicity of the complexes was evaluated against A549, MDA-MB-231 and HaCat cells by MTT assay. Complexes (1) and (2), which are very active against triple negative MDA-MB-231, were subjected to further biological tests with this cell line. The cytotoxic activity triggered by the complexes was confirmed by clonogenic assay. Cell cycle analyses demonstrated marked anti-proliferative effects, especially at the G0/G1 and S phases. The morphological detection of apoptosis and necrosis - HO/PI and Annexin V-FITC/PI assay, elucidated that the type of cell death triggered by these complexes was probably by apoptosis. The in vivo toxicological assessment performed on zebrafish embryos revealed that complexes (1) and (2) did not present embryotoxic or toxic effects during embryonic and larval development showing that they are promising new prototypes of safer and more effective drugs for triple negative breast cancer treatment.


Assuntos
Antineoplásicos/síntese química , Complexos de Coordenação/síntese química , Substâncias Intercalantes/síntese química , Pirimidinas/química , Rutênio/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/toxicidade , DNA/metabolismo , Desenho de Drogas , Técnicas Eletroquímicas/métodos , Humanos , Substâncias Intercalantes/farmacologia , Substâncias Intercalantes/toxicidade , Estrutura Molecular , Relação Estrutura-Atividade , Termodinâmica , Peixe-Zebra/embriologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA