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1.
Molecules ; 26(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917290

RESUMO

This paper reports on the synthesis and characterization of two new polypyridyl-hydrazone Schiff bases, (E)-N'-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)thiophene-2-carbohydrazide (L1) and (E)-N'-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)furan-2-carbohydrazide (L2), and their two Ru(II) complexes of the general formula [RuCl(DMSO)(phen)(Ln)](PF6). Considering that hydrazides are a structural part of severa l drugs and metal complexes containing phenanthroline derivatives are known to interact with DNA and to exhibit antitumor activity, more potent anticancer agents can be obtained by covalently linking the thiophene acid hydrazide or the furoic acid hydrazide to a 1,10-phenanthroline moiety. These ligands and the Ru(II) complexes were characterized by elemental analyses, electronic, vibrational, 1H NMR, and ESI-MS spectroscopies. Ru is bound to two different N-heterocyclic ligands. One chloride and one S-bonded DMSO in cis-configuration to each other complete the octahedral coordination sphere around the metal ion. The ligands are very effective in inhibiting cellular growth in a chronic myelogenous leukemia cell line, K562. Both complexes are able to interact with DNA and present moderate cytotoxic activity, but 5 min of UV-light exposure increases cytotoxicity by three times.


Assuntos
Complexos de Coordenação/farmacologia , Hidrazonas/farmacologia , Luz , Fenantrolinas/farmacologia , Rutênio/farmacologia , Animais , Bovinos , Morte Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , DNA/metabolismo , Dimetil Sulfóxido/química , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Células K562 , Ligantes , Fenantrolinas/síntese química , Fenantrolinas/química , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray
2.
Molecules ; 26(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807680

RESUMO

N,N'-chelate organoboron compounds have been successfully applied in bioimaging, organic light-emitting diodes (OLEDs), functional polymer, photocatalyst, electroluminescent (EL) devices, and other science and technology areas. However, the concise and efficient synthetic methods become more and more significant for material science, biomedical research, or other practical science. Here, we summarized the organoboron-N,N'-chelate derivatives and showed the different routes of their syntheses. Traditional methods to synthesize N,N'-chelate organoboron compounds were mainly using bidentate ligand containing nitrogen reacting with trivalent boron reagents. In this review, we described a series of bidentate ligands, such as bipyridine, 2-(pyridin-2-yl)-1H-indole, 2-(5-methyl-1H-pyrrol-2-yl)quinoline, N-(quinolin-8-yl)acetamide, 1,10-phenanthroline, and diketopyrrolopyrrole (DPP).


Assuntos
Compostos de Boro/síntese química , Indóis/química , Piridinas/química , Quinolinas/química , Isocianatos/química , Ligantes , Fenantrolinas/química
3.
Inorg Chem ; 60(2): 1248-1256, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33400522

RESUMO

Cu, Zn, and amyloid-ß (Aß) peptides play an important role in the etiology of Alzheimer's disease (AD). Their interaction indeed modifies the self-assembly propensity of the peptide that is at the origin of the deposition of insoluble peptide aggregates in the amyloid plaque, a hallmark found in AD brains. Another even more important fallout of the Cu binding to Aß peptide is the formation of reactive oxygen species (ROS) that contributes to the overall oxidative stress detected in the disease and is due to the redox ability of the Cu ions. Many therapeutic approaches are currently developed to aid fighting against AD, one of them targeting the redox-active Cu ions. Along this research line, we report in the present article the use of a phenanthroline-based peptide-like ligand (L), which is able to withdraw Cu from Aß and redox-silence it in a very stable 4N Cu(II) binding site even in the presence of Zn(II). In addition and in contrast to what is usually observed, the presence of excess of L lessens the searched effect of ROS production prevention, but it is counterbalanced by the co-presence of Zn(II). To explain such unprecedented trends, we proposed a mechanism that involves the redox reaction between Cu(II)L and Cu(I)L2. We thus illustrated (i) how speciation and redox chemistry can weaken the effect of a ligand that would have appeared perfectly suitable if only tested in a 1:1 ratio and on CuAß and (ii) how Zn overcomes the undesired lessening of ROS arrest due to excess of ligand. In brief, we have shown how working in biologically relevant conditions is important for the understanding of all of the reactions at play and this must be taken into consideration for the further rational design of ligands aiming to become drug candidates.


Assuntos
Peptídeos beta-Amiloides/química , Cobre/isolamento & purificação , Zinco/química , Peptídeos beta-Amiloides/metabolismo , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/metabolismo , Ligantes , Conformação Molecular , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Fenantrolinas/química , Fenantrolinas/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Zinco/metabolismo
4.
Phys Chem Chem Phys ; 23(5): 3361-3376, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33502401

RESUMO

The stability of c-KIT G-quadruplex DNA via ligands has been a significant concern in the growing field of cancer therapy. Thus, it is very important to understand the mechanism behind the high binding affinity of the small drug molecules on the c-KIT G-quadruplex DNA. In this study, we have investigated the binding mode and pathway of the APTO-253 ligand on the c-KIT G-quadruplex DNA employing a total of 10 µs all atom molecular dynamics simulations and further 8.82 µs simulations via the umbrella sampling method using both OL15 and BSC1 latest force fields for DNA structures. From the cluster structure analysis, mainly three binding pathways i.e., top, bottom and side loop stacking modes are identified. Moreover, RMSD, RMSF and 2D-RMSD values indicate that the c-KIT G-quadruplex DNA and APTO-253 molecules are stable throughout the simulation run. Furthermore, the number of hydrogen bonds in each tetrad and the distance between the two central K+ cations confirm that the c-KIT G-quadruplex DNA maintains its conformation in the process of complex formation with the APTO-253 ligand. The binding free energies and the minimum values in the potential of mean forces suggest that the binding processes are energetically favorable. Furthermore, we have found that the bottom stacking mode is the most favorable binding mode among all the three modes for the OL15 force field. However, for the BSC1 force field, both the top and bottom binding modes of the APTO-253 ligand in c-KIT G-quadruplex DNA are comparable to each other. To investigate the driving force for the complex formation, we have noticed that the van der Waals (vdW) and π-π stacking interactions are mainly responsible. Our detailed studies provide useful information for the discovery of novel drugs in the field of stabilization of G-quadruplex DNAs.


Assuntos
DNA/metabolismo , Quadruplex G , Imidazóis/metabolismo , Fenantrolinas/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Sítios de Ligação , DNA/química , DNA/genética , Humanos , Ligação de Hidrogênio , Imidazóis/química , Simulação de Dinâmica Molecular , Fenantrolinas/química , Eletricidade Estática
5.
Eur J Med Chem ; 213: 113172, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33516984

RESUMO

The synthesis and biological evaluation of a series of phenanthroline-based visible-light-activated manganese(I) carbon-monoxide-releasing molecules (PhotoCORMs) against ESKAPE bacteria and bacterial biofilms is reported. Four carbonyl compounds of general formula fac-[Mn(N∧N)(CO)3(L)] have been synthesized and characterized. Despite being thermally stable in the absence of light, these PhotoCORMs readily release CO upon blue (435-450 nm) LED light irradiation as confirmed by spectrophotometric CO releasing experiments (Mb Assay). The antibacterial activity of the four PhotoCORMs has been investigated against a panel of ESKAPE bacteria. The compounds 1-3 were found to be effective antibacterials at low concentrations against multidrug-resistant Klebsiella pneumoniae and Acinetobacter baumannii when photoactivated with blue-light. In addition, the PhotoCORMs 1-2 were found to inhibit the formation of Klebsiella pneumoniae and Acinetobacter baumannii bacterial biofilms at low concentrations (MIC = 4-8 µg/mL), turning out to be promising candidates to combat antimicrobial resistance. The antibacterial and biofilm inhibitory effect of the PhotoCORMs is plausibly due to the release of CO as well as the formation of phenanthroline photo-by-products as revealed by spectroscopy and microbiology experiments.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Desenvolvimento de Medicamentos , Klebsiella pneumoniae/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Monóxido de Carbono/química , Monóxido de Carbono/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Manganês/química , Manganês/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenantrolinas/química , Fenantrolinas/farmacologia , Processos Fotoquímicos , Relação Estrutura-Atividade
6.
ACS Appl Mater Interfaces ; 13(1): 298-305, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33382593

RESUMO

Most DNA-based electrochemiluminescence (ECL) biosensors are established through the self-assembly of thiolated single-stranded DNA (ssDNA) probes on the Au electrode surface. Because of this random assembly process, a significant discrepancy exists in the distribution of a modified DNA film on different electrodes, which greatly affects the reproducibility of a biosensor. In this study, a porous bovine serum albumin (BSA) layer was first modified on the electrode surface, which can improve the position distribution and spatial orientation of the self-assembly ssDNA probe. It was then coupled with hyperbranched rolling circle amplification to develop the high-reproducibility-and-sensitivity ECL biosensor for human papillomavirus 16 E6 and E7 oncogene detection. In the presence of the target DNA, the surface of the electrode accumulates abundant amplified products through reaction, which contain double-stranded DNA (dsDNA) fragments of different lengths, followed by plentiful dichlorotris (1,10-phenanthroline) ruthenium(II) hydrate (Ru(phen)32+, acting as an ECL indicator) insertion into grooves of dsDNA fragments, and a strong signal can be detected. There is a linear relationship between the signal and the target concentration range from 10 fM to 15 pM, and the detection limit is 7.6 fM (S/N = 3). After the BSA modification step, the relative standard deviation was reduced from 9.20 to 3.96%, thereby achieving good reproducibility. The proposed ECL strategy provides a new method for constructing high-reproducibility-and-sensitivity ECL biosensors.


Assuntos
Técnicas Biossensoriais/métodos , Papillomavirus Humano 16/isolamento & purificação , Proteínas Oncogênicas Virais/análise , Proteínas E7 de Papillomavirus/análise , Proteínas Repressoras/análise , Soroalbumina Bovina/química , Animais , Bovinos , Colo do Útero/virologia , Sondas de DNA/química , Sondas de DNA/genética , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Técnicas Eletroquímicas/métodos , Feminino , Papillomavirus Humano 16/química , Humanos , Limite de Detecção , Substâncias Luminescentes , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico , Proteínas Oncogênicas Virais/genética , Compostos Organometálicos/química , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/diagnóstico , Fenantrolinas/química , Proteínas Repressoras/genética , Reprodutibilidade dos Testes , Rutênio/química
7.
Food Chem ; 338: 127800, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798815

RESUMO

For the first time, a method is proposed for colorimetric determination of reducing sugars in cachaça employing digital image and a smartphone as detector. The method was based on the reduction of Cu(II) to Cu(I) by sugars and followed by the formation of a colored Cu(I)-Neocuproine complex. A calibration curve was linear from 0.1 to 15 g L-1 for glucose and fructose with limits of detection of 0.012 g L-1 and 0.010 g L-1, respectively. It was observed that the non-aged cachaças, known for having inferior flavors and aromas, had a reducing sugar content three times higher than the aged cachaças, once a common practice among producers is to add sugar to adjust sensory deficits in the final product. Furthermore, the method is simple, does not require complex technical knowledge and it could be used as a tool to check possible fraud, adulteration or non-compliance to the law.


Assuntos
Bebidas Alcoólicas/análise , Análise de Alimentos/instrumentação , Análise de Alimentos/métodos , Smartphone , Açúcares/análise , Colorimetria/instrumentação , Colorimetria/métodos , Cobre/química , Desenho de Equipamento , Contaminação de Alimentos/análise , Frutose/análise , Glucose/análise , Fenantrolinas/química , Saccharum
8.
Biotechnol Appl Biochem ; 67(4): 536-540, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376255

RESUMO

Protein dimerization often occurs in many biological systems as to provide structural and functional advantages. A tris(5-iodoacetamido-1,10-phenanthroline)Ruthenium(II) complex was shown to promote the covalent dimerization of a P450 BM3 heme domain mutant containing a surface exposed non-native single cysteine residue. The formation of homodimeric species was confirmed by protein gel electrophoresis, mass spectrometry and UV-Vis spectroscopy. The dimeric species could be separated from the monomer and aggregates by size-exclusion chromatography. Docking simulation reveals a plausible structure with two proteins covalently conjugated to the inorganic compound.


Assuntos
Complexos de Coordenação/química , Sistema Enzimático do Citocromo P-450/química , Heme/química , Fenantrolinas/química , Multimerização Proteica , Rutênio/química , Substituição de Aminoácidos , Sistema Enzimático do Citocromo P-450/genética , Mutação de Sentido Incorreto , Domínios Proteicos
9.
Food Chem ; 328: 127099, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474238

RESUMO

In this study, we developed a competitive colorimetric immunoassay for qualitative detection of DAN based on oxidation of iron (Ⅱ) (Fe2+) in the presence of glucose oxidase (GOx) and color change induced by Fe2+-phenanthroline (Phen) chromogenic system. Streptavidin (SA) acted as a linker between biotinylated anti-DAN-monoantibody (bio-mAb) and biotinylated GOx (bio-GOx) to form the immunocomplexes bio-mAb-SA-bio-GOx. In the absence of DAN, the immunocomplexes bio-mAb-SA-bio-GOx combining with coated DAN-ovalbumin (DAN-OVA) will be immobilized and catalyze glucose to produce H2O2. Fe2+ is oxidized to Fe3+ by H2O2, giving rise to a colorless result. In the presence of DAN, Fe2+ produces a chelation reaction with Phen, leading to orange-red color. Under optimal conditions, the detection limit (LOD) by naked eyes was 2.5 ng mL-1 in milk, chicken, beef, and pork samples. Low LOD, no matrix effect, and no signal reader requirement make it possibly applied to quickly screen DAN on site.


Assuntos
Técnicas Biossensoriais/métodos , Colorimetria/métodos , Fluoroquinolonas/análise , Glucose Oxidase/metabolismo , Imunoensaio/métodos , Quelantes de Ferro/química , Fenantrolinas/química , Biocatálise , Catálise , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Fluoroquinolonas/química , Glucose/química , Glucose Oxidase/química , Peróxido de Hidrogênio/química , Limite de Detecção
10.
Dalton Trans ; 49(16): 5264-5275, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32242564

RESUMO

New silver(i) compounds containing 2-formylpyridine-N(4)-R-thiosemicarbazones and 1,10-phenanthroline (phen) were synthesized and characterized by spectroscopic techniques (IR and NMR), elemental analysis, ESI-MS and molar conductance measurements. In these complexes, both phen and thiosemicarbazone ligands are coordinated in a chelating bidentate fashion. Compounds 1-3 not only showed good in vitro antiproliferative activity against human lung (A549) and breast tumor cells (MDA-MB-231 and MCF-7), with IC50 values ranging from 1.49 to 20.90 µM, but were also demonstrated to be less toxic towards human breast non-tumor cells (MCF-10A). Cellular uptake studies indicated that compounds 1-3 were taken up by the MDA-MB-231 cells in 6 hours. Cell death assays in the MDA-MB-231 cells were conducted with compound 1 aiming to evaluate its effects on cell morphology, induction of apoptosis, the cell cycle, reactive oxygen species (ROS) formation and mitochondrial membrane potential (Δψm). Compound 1 caused morphological changes, such as cell shrinkage and rounding, increased the sub-G1 phase population, and induced apoptotic cell death, ROS formation and loss of mitochondrial membrane potential (Δψm). DNA binding results revealed that 1 interacted with the ct-DNA minor groove. Complexes 1-3 also exhibited good in vitro activity against M. tuberculosis H37Rv, with MIC values ranging from 3.37 to 4.65 µM.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Fenantrolinas/farmacologia , Prata/farmacologia , Tiossemicarbazonas/farmacologia , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estrutura Molecular , Fenantrolinas/química , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Relação Estrutura-Atividade , Tiossemicarbazonas/química
11.
Inorg Chem ; 59(7): 4527-4535, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32181663

RESUMO

The in-gel detection of proteins for various proteomic experiments is commonly done with the fluorescent RuII tris(bathophenanthroline disulfonate) complex (Ru(BPS)3), which is more cost-effective compared to commercial Ru-based formulations but requires tedious procedures for its preparation and strongly acidic staining conditions. Herein, we report the synthesis and characterization of heteroleptic RuII complexes Ru(BPS)2(BP) and Ru(BPS)(BP)2 containing bathophenanthroline (BP) and bathophenanthroline disulfonate disodium salt (BPS) in comparison with Ru(BPS)3. It was shown by fluorescent and UV-vis measurements that novel RuII complexes were excitable in both UV and visible light, close to emission bands of classical lasers, which is important for successful in-gel protein detection. Novel fluorescent dyes demonstrated improved protein detection in comparison with commercially available SYPRO Ruby staining solution. In addition, unlike commonly used staining protocols, staining with Ru(BPS)(BP)2 can be performed at nearly neutral pH, thereby reducing artificial post-translational modifications (PTMs).


Assuntos
Complexos de Coordenação/química , Corantes Fluorescentes/química , Fenantrolinas/química , Coloração e Rotulagem/métodos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Eletroforese em Gel de Poliacrilamida/métodos , Corantes Fluorescentes/síntese química , Humanos , Fenantrolinas/síntese química , Proteínas/análise , Proteínas/química , Rutênio/química
12.
Chem Commun (Camb) ; 56(27): 3863-3866, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32134088

RESUMO

Two DNA conjugates modified with ethylenediaminetetraacetic acid and 1,10-phenanthroline were prepared as a pair of split probes. They were designed to form a duplex with their auxiliary groups facing each other, providing a microenvironment to accommodate lanthanide ions. The luminescent signal was amplified by catalytic duplex formation based on an entropy-driven DNA circuit.


Assuntos
DNA/química , Ácido Edético/química , Európio/química , Substâncias Luminescentes/química , Fenantrolinas/química , Térbio/química , Catálise , Entropia , Luminescência
13.
Chem Commun (Camb) ; 56(23): 3421-3424, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32096501

RESUMO

A self-catalytic ampicillin-metal (Fe3+)-organic gels (AMP-MOGs (Fe))-H2O2 CL system, which is not influenced by transition metal ions, was studied. A method for CL detection of Staphylococcus aureus (S. aureus) based on the AMP-MOGs (Fe)-H2O2 CL system was achieved. A superior detection limit of 31 CFU mL-1 toward S. aureus was obtained with near-zero background noise.


Assuntos
Ampicilina/química , Géis/química , Peróxido de Hidrogênio/química , Ferro/química , Staphylococcus aureus/isolamento & purificação , Anticorpos/imunologia , Catálise , Imunoensaio/métodos , Limite de Detecção , Luminescência , Medições Luminescentes/métodos , Fenantrolinas/química , Staphylococcus aureus/imunologia
14.
Molecules ; 25(3)2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32046362

RESUMO

A series of water-soluble copper(II) complexes based on 2,9-dimethyl-1,10-phenanthroline (dmphen) and mixed-ligands, containing PTA=O (1,3,5-triaza-7-phosphaadamantane-7-oxide) have been synthesized and fully characterized. Two types of complexes have been obtained, monocationic [Cu(NO3)(O-PTA=O)(dmphen)][PF6] (1), [Cu(Cl)(dmphen)2][PF6] (2), and neutral [Cu(NO3)2(dmphen)] (3). The solid-state structures of all complexes have been determined by single-crystal X-ray diffraction. Magnetic studies for the complex 1-3 indicated a very weak antiferromagnetic interaction between copper(II) ions in crystal lattice. Complexes were successfully evaluated for their cytotoxic activities on the normal human dermal fibroblast (NHDF) cell line and the antitumor activity using the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa), colon (LoVo), and breast adenocarcinoma (MCF-7) cell lines. Complexes 1 and 3 revealed lower toxicity to NHDF than A549 and HeLa cells, meanwhile compound 2 appeared to be more toxic to NHDF cell line in comparison to all cancer lines. Additionally, interactions between the complexes and human apo-transferrin (apo-Tf) using fluorescence and circular dichroism (CD) spectroscopy were also investigated. All compounds interacted with apo-transferrin, causing same changes of the protein conformation. Electrostatic interactions dominate in the 1/2 - apo- Tf systems and hydrophobic and ionic interactions in the case of 3.


Assuntos
Adamantano/química , Antineoplásicos/síntese química , Apoproteínas/química , Complexos de Coordenação/síntese química , Cobre/química , Fenantrolinas/química , Transferrina/química , Células A549 , Adamantano/análogos & derivados , Antineoplásicos/farmacologia , Apoproteínas/metabolismo , Cátions Bivalentes , Cátions Monovalentes , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Concentração Inibidora 50 , Cinética , Células MCF-7 , Óxidos/química , Ligação Proteica , Termodinâmica , Transferrina/metabolismo
15.
ACS Appl Mater Interfaces ; 12(3): 3465-3473, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31913004

RESUMO

The high-resolution technique transmission electron microscopy (TEM), with OsO4 as the traditional fixative, is an essential tool for cell biology and medicine. Although OsO4 has been extensively used, it is far from perfect because of its high volatility and toxicity. Os(II) polypyridyl complexes like [Os(phen)2(dppz)]2+ (phen = 1,10-phenanthroline; dppz = dipyridophenazine) are not only the well-known molecular DNA "light-switches" but also the potential ideal candidates for TEM studies. Here, we report that the cell-impermeable cationic [Os(phen)2(dppz)]2+ can be preferentially delivered into the live-cell nucleus through ion-pairing with chlorophenolate counter-anions, where it functions as an unparalleled enantioselective nuclear DNA imaging reagent especially suitable for correlative light and electron microscopy (CLEM) studies in both living and fixed cells, which can clearly visualize chromosome aggregation and decondensation during mitosis simultaneously. We propose that the chiral Os(II) polypyridyl complexes can be used as a distinctive group of enantioselective high-resolution CLEM imaging probes for live-cell nuclear DNA studies.


Assuntos
Núcleo Celular/química , DNA/química , Tetróxido de Ósmio/química , Fenantrolinas/química , Animais , Linhagem Celular Tumoral , Núcleo Celular/genética , DNA/genética , Humanos , Microscopia , Microscopia Eletrônica de Transmissão , Mitose , Estereoisomerismo
16.
Molecules ; 25(3)2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991806

RESUMO

Three series of fused pyrrolophenanthroline derivatives were designed as analogues of phenstatin and synthesized in two steps starting with 1,7-phenanthroline, 4,7-phenanthroline and 1,10-phenanthroline, respectively. Two (Compounds 8a and 11c) of the four compounds tested against a panel of sixty human cancer cell lines of the National Cancer Institute (NCI) exhibited significant growth inhibition activity on several cell lines. Compound 11c showed a broad spectrum in terms of antiproliferative efficacy with GI50 values in the range of 0.296 to 250 µM. Molecular docking studies indicated that Compounds 8a and 11c are accommodated in the colchicine binding site of tubulin in two different ways.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Técnicas de Química Sintética , Desenho de Fármacos , Modelos Moleculares , Fenantrolinas/química , Fenantrolinas/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Fenantrolinas/síntese química , Relação Estrutura-Atividade
17.
Molecules ; 25(2)2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940835

RESUMO

Two novel pinene-type ligands have been synthesized and their tautomeric and self-associating behavior studied in solution and in the solid state. The first ligand, an acetylated derivative of 5,6-pinene-bipyridine, displays keto-enol tautomerism in solution. This tautomeric equilibrium was studied by NMR and UV-Vis spectroscopy in various solvents, and the results were compared with the ones obtained through DFT calculations. The second ligand was obtained by an unusual oxidation of the phenanthroline unit of a pinene-phenanthroline derivative. This compound exists as a single tautomer in solution and aggregates both in solution (as observed by NMR) and in the solid state through H-bonding as observed by X-ray structure determination and confirmed by DFT studies.


Assuntos
2,2'-Dipiridil/química , Monoterpenos Bicíclicos/química , Fenantrolinas/química , 2,2'-Dipiridil/síntese química , Cristalografia por Raios X , Dimerização , Dimetil Sulfóxido/química , Ligação de Hidrogênio , Conformação Molecular , Fenantrolinas/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Soluções/química , Estereoisomerismo , Temperatura
18.
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
19.
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
20.
Metallomics ; 12(1): 65-78, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31720645

RESUMO

Herein we report an in-depth study on the cytotoxic mechanism of action of four developmental cytotoxic copper(ii) complexes: [Cu(phen)2]2+ (Cu-Phen); [Cu(DPQ)(Phen)]2+ (Cu-DPQ-Phen); [Cu(DPPZ)(Phen)]2+; and [Cu(DPPN)(Phen)]2+ (where Phen = 1,10-phenanthroline, DPQ = dipyrido[3,2-f:2',3'-h]quinoxaline, DPPZ = dipyrido[3,2-a:2',3'-c]phenazine, and DPPN = benzo[i]dipyrido[3,2-a:2',3'-c]phenazine). This complex class is known for its DNA intercalative properties and recent evidence-derived from an in vivo proteomic study-supports the potential targeting of mitochondrial function. Therefore, we focused on mitochondrial-mediated apoptosis related to cytotoxic activity and the potential impact these agents have on mitochondrial function. The Cu(ii) complexes demonstrated superior activity regardless of aromatic extension within the phenazine ligand to the previously demonstrated activity of cisplatin. Unique toxicity mechanisms were also identified in prior demonstrated cisplatin sensitive and resistant cell lines. Double strand breaks in genomic DNA, quantified by γH2AX foci formation, were then coupled with apoptotic gene expression to elucidate the mechanisms of cell death. These results indicate that while DNA damage-induced apoptosis by BAX, XIAP and caspase-9 and -3 expression is moderate for the Cu(ii) complexes when compared to cisplatin, protein targets independent of DNA exert a multimodal mechanistic effect. Significantly, mitochondrial gene expression of oxidative stress, protease expression, and fission/fusion processes-upregulated HMOX, DRP1 and LON, respectively-indicated an increased oxidative damage associated with compromised mitochondrial health upon exposure to these agents. These data support a unique mode of action by these complexes and provide valuable evidence of the developmental potential of these therapeutic inorganic complexes.


Assuntos
Cobre/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fenantrolinas/química , Fenantrolinas/farmacologia , Fenazinas/química , Fenazinas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Citometria de Fluxo , Humanos , Células MCF-7 , Microscopia Confocal , Oxirredução/efeitos dos fármacos
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