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1.
Int J Mol Sci ; 21(15)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32717853

RESUMO

As SARS-CoV-2 is spreading rapidly around the globe, adopting proper actions for confronting and protecting against this virus is an essential and unmet task. Reactive oxygen species (ROS) promoting molecules such as peroxides are detrimental to many viruses, including coronaviruses. In this paper, metal decorated single-wall carbon nanotubes (SWCNTs) were evaluated for hydrogen peroxide (H2O2) adsorption for potential use for designing viral inactivation surfaces. We employed first-principles methods based on the density functional theory (DFT) to investigate the capture of an individual H2O2 molecule on pristine and metal (Pt, Pd, Ni, Cu, Rh, or Ru) decorated SWCNTs. Although the single H2O2 molecule is weakly physisorbed on pristine SWCNT, a significant improvement on its adsorption energy was found by utilizing metal functionalized SWCNT as the adsorbent. It was revealed that Rh-SWCNT and Ru-SWCNT systems demonstrate outstanding performance for H2O2 adsorption. Furthermore, we discovered through calculations that Pt- and Cu-decorated SWNCT-H2O2 systems show high potential for filters for virus removal and inactivation with a very long shelf-life (2.2 × 1012 and 1.9 × 108 years, respectively). The strong adsorption of metal decorated SWCNTs and the long shelf-life of these nanomaterials suggest they are exceptional candidates for designing personal protection equipment against viruses.


Assuntos
Betacoronavirus/efeitos dos fármacos , Desinfetantes/farmacologia , Peróxido de Hidrogênio/análise , Nanotubos de Carbono/química , Adsorção , Infecções por Coronavirus/prevenção & controle , Teoria da Densidade Funcional , Desinfetantes/química , Estabilidade de Medicamentos , Humanos , Ferro/química , Ferro/farmacologia , Pandemias/prevenção & controle , Equipamento de Proteção Individual , Platina/química , Platina/farmacologia , Pneumonia Viral/prevenção & controle , Ródio/química , Ródio/farmacologia , Rutênio/química , Rutênio/farmacologia , Inativação de Vírus
2.
Nat Commun ; 11(1): 3262, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591538

RESUMO

The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E')-4,4'-bisstyryl-2,2'-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.


Assuntos
Complexos de Coordenação/uso terapêutico , Desenho de Fármacos , Fotoquimioterapia , Fótons , Rutênio/química , Animais , Proliferação de Células , Sobrevivência Celular , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Feminino , Células HeLa , Humanos , Camundongos Nus , Oxigênio Singlete/química , Análise Espectral , Esferoides Celulares/patologia
3.
Chemosphere ; 256: 127077, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32438124

RESUMO

The ultra-deep adsorptive desulfurization (ppb level) of benzene remains a challenging subject with the need to construct efficient adsorbent systems. Herein, a kind of ruthenium-based adsorbent functionalized with bimetallic Ru-Al was rationally designed using Al2O3 as support (denoted as 0.8%Ru-1.2%Al/Al2O3). It was found that the co-anchoring of Ru and Al species endows the Ru-based adsorbent unique adsorption capability, which is able to completely eliminate sulfur compounds in benzene, and exhibiting a much higher breakthrough sulfur capacity than that of the 0.8%Ru/Al2O3. Remarkably, under the industrial experiment conditions, 0.8%Ru-1.2%Al/Al2O3 exhibited excellent long-term stability for more than 1200 h, showing the potential for industrial application. Various characterization techniques, including BET, XRD, SEM, TEM, TPD-MS, TPR and XPS, were used to investigate the correlation between the adsorption performance and the microstructure of the adsorbents. Over 0.8%Ru-1.2%Al/Al2O3, the ultra-thin aluminum additive is beneficial to improve the dispersion of Ru species, which therefore exhibits desirable desulfurization efficiency. Moreover, the enhanced performance is also correlated to the presence of the suitable Ru active centers generated from the selective coverage by Al species. It leads to an optimal exposure of the Ru active centers, which would facilitate the interaction of S-Ru and the improvement of the desulfurization activity.


Assuntos
Benzeno/análise , Rutênio/química , Adsorção , Alumínio , Óxido de Alumínio/química , Espaços Confinados , Enxofre , Compostos de Enxofre
4.
J Med Chem ; 63(10): 5568-5584, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32319768

RESUMO

Chemotherapy remains one of the dominant treatments to cure cancer. However, due to the many inherent drawbacks, there is a search for new chemotherapeutic drugs. Many classes of compounds have been investigated over the years to discover new targets and synergistic mechanisms of action including multicellular targets. In this work, we designed a new chemotherapeutic drug candidate against cancer, namely, [Ru(DIP)2(sq)](PF6) (Ru-sq) (DIP = 4,7-diphenyl-1,10-phenanthroline; sq = semiquinonate ligand). The aim was to combine the great potential expressed by Ru(II) polypyridyl complexes and the singular redox and biological properties associated with the catecholate moiety. Experimental evidence (e.g., X-ray crystallography, electron paramagnetic resonance, electrochemistry) demonstrates that the semiquinonate is the preferred oxidation state of the dioxo ligand in this complex. The biological activity of Ru-sq was then scrutinized in vitro and in vivo, and the results highlight the promising potential of this complex as a chemotherapeutic agent against cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/metabolismo , Quinonas/química , Quinonas/metabolismo , Rutênio/química , Rutênio/metabolismo , Animais , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Feminino , Células HeLa , Humanos , Ligantes , Camundongos , Camundongos Nus , Oxirredução/efeitos dos fármacos , Quinonas/farmacologia , Rutênio/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
5.
Chem Commun (Camb) ; 56(20): 3019-3022, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32048647

RESUMO

Nucleus-targeting NPs based on RuO2 (RuO2NPs) were developed by controlling the size and the surface charge of nanoparticles (NPs). This study not only demonstrates a facile approach for the fabrication of ultrasmall CS-RuO2NPs with good biocompatibility and excellent photothermal properties but also their unique potential for the nucleus-targeted low-temperature PTT.


Assuntos
Nanopartículas/química , Imagem Óptica , Óxidos/química , Técnicas Fotoacústicas , Rutênio/química , Temperatura , Núcleo Celular/efeitos dos fármacos , Humanos , Raios Infravermelhos , Células MCF-7 , Óxidos/farmacologia , Tamanho da Partícula , Fototerapia , Rutênio/farmacologia , Propriedades de Superfície
6.
Chem Commun (Camb) ; 56(20): 3069-3072, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32049075

RESUMO

Niacin-ligated platinum(iv)-ruthenium(ii) chimeric complexes (PtRu 1-4) have been synthesized and evaluated for their antitumor performance. Using the optimal complex, PtRu-1, we show that this water-soluble chimeric prodrug not only potently inhibits the metastasis and proliferation of tumor cells but also has an unexpectedly higher safety margin in animals compared with the traditionally-used, clinically approved drug cisplatin.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Niacina/farmacologia , Platina/farmacologia , Rutênio/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Cisplatino/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Niacina/química , Platina/química , Rutênio/química , Relação Estrutura-Atividade
7.
Chemistry ; 26(20): 4489-4495, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32073730

RESUMO

It is challenging to design metal catalysts for in situ transformation of endogenous biomolecules with good performance inside living cells. Herein, we report a multifunctional metal catalyst, ruthenium-coordinated oligo(p-phenylenevinylene) (OPV-Ru), for intracellular catalysis of transfer hydrogenation of nicotinamide adenine dinucleotide (NAD+ ) to its reduced format (NADH). Owing to its amphiphilic characteristic, OPV-Ru possesses good self-assembly capability in water to form nanoparticles through hydrophobic interaction and π-π stacking, and numerous positive charges on the surface of nanoparticles displayed a strong electrostatic interaction with negatively charged substrate molecules, creating a local microenvironment for enhancing the catalysis efficiency in comparison to dispersed catalytic center molecule (TOF value was enhanced by about 15 fold). OPV-Ru could selectively accumulate in the mitochondria of living cells. Benefiting from its inherent fluorescence, the dynamic distribution in cells and uptake behavior of OPV-Ru could be visualized under fluorescence microscopy. This work represents the first demonstration of a multifunctional organometallic complex catalyzing natural hydrogenation transformation in specific subcellular compartments of living cells with excellent performance, fluorescent imaging ability, specific mitochondria targeting and good chemoselectivity with high catalysis efficiency.


Assuntos
Complexos de Coordenação/química , Mitocôndrias/química , Polivinil/química , Rutênio/química , Catálise , Hidrogenação , Interações Hidrofóbicas e Hidrofílicas , Mitocôndrias/metabolismo , Nanopartículas , Água
8.
Chemistry ; 26(22): 4997-5009, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32065454

RESUMO

Cancer is one of the main causes of death worldwide. Chemotherapy, despite its severe side effects, is to date one of the leading strategies against cancer. Metal-based drugs present several potential advantages when compared to organic compounds and they have gained trust from the scientific community after the approval on the market of the drug cisplatin. Recently, we reported the ruthenium complex ([Ru(DIP)2 (sq)](PF6 ) (where DIP is 4,7-diphenyl-1,10-phenantroline and sq is semiquinonate) with a remarkable potential as chemotherapeutic agent against cancer, both in vitro and in vivo. In this work, we analyse a structurally similar compound, namely [Ru(DIP)2 (mal)](PF6 ), carrying the flavour-enhancing agent approved by the FDA, maltol (mal). To possess an FDA approved ligand is crucial for a complex, whose mechanism of action might include ligand exchange. Herein, we describe the synthesis and characterisation of [Ru(DIP)2 (mal)](PF6 ), its stability in solutions and under conditions that resemble the physiological ones, and its in-depth biological investigation. Cytotoxicity tests on different cell lines in 2D model and on HeLa MultiCellular Tumour Spheroids (MCTS) demonstrated that our compound has higher activity than cisplatin, inspiring further tests. [Ru(DIP)2 (mal)](PF6 ) was efficiently internalised by HeLa cells through a passive transport mechanism and severely affected the mitochondrial metabolism.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Complexos de Coordenação/farmacologia , Pironas/farmacologia , Rutênio/química , Antineoplásicos/química , Cisplatino/química , Complexos de Coordenação/química , Células HeLa , Humanos , Ligantes , Estrutura Molecular , Pironas/química , Rutênio/farmacologia
9.
Dalton Trans ; 49(10): 3243-3252, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32096513

RESUMO

A series of cationic Ru(ii)(η6-p-cymene) complexes with thioether-functionalised N-heterocyclic carbene ligands have been prepared and fully characterized. Steric and electronic influence of the R thioether substituent on the coordination of the sulfur atom was investigated. The molecular structure of three of them has been determined by means of X-ray diffractrometry and confirmed the bidentate (κ2-C,S) coordination mode of the ligand. Interestingly, only a single diastereomer, as an enantiomeric couple, was observed in the solid state for complexes 1c, 1i and 1j. DFT calculations established a low energy inversion barrier between the two diastereomers through a sulfur pyramidal inversion pathway with R donating group while a dissociative/associative mechanism is more likely with R substituents that contain electron withdrawing group, thus suggesting that the only species observed by the 1H-NMR correspond to an average resonance position of a fluxional mixtures of isomers. All these complexes were found to catalyse the oxydant-free double dehydrogenation of primary amine into nitrile. Ru complex bearing NHC-functionalised S-tBu group was further investigated in a wide range of amines and was found more selective for alkyl amine substrates than for benzylamine derivatives. Finally, preliminary results of the biological effects on various human cancer cells of four selected Ru complexes are reported.


Assuntos
Complexos de Coordenação/química , Rutênio/química , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Humanos , Ligantes , Rutênio/farmacologia , Sulfetos/química
10.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936104

RESUMO

Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5'-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Diaminas/química , Compostos Organometálicos/farmacologia , Rutênio/química , Sulfonamidas/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Quelantes/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Cristalografia por Raios X , Diaminas/farmacologia , Etilenodiaminas/química , Etilenodiaminas/farmacologia , Guanosina Monofosfato/metabolismo , Células HT29 , Humanos , Concentração de Íons de Hidrogênio , Cinética , Ligantes , Modelos Moleculares , Compostos Organometálicos/química , Rutênio/farmacologia , Sulfonamidas/farmacologia
11.
Chem Commun (Camb) ; 56(14): 2087-2090, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31967623

RESUMO

A dual-emissive tris-heteroleptic ruthenium complex is designed, synthesized and applied for the ratiometric photoluminescent detection of amyloid-ß (Aß) aggregation in both steady and transient states. The Aß aggregation is supported by transmission electron microscopy and confocal laser scanning microscopy analysis. In addition, molecular docking calculations have been performed to gain insights into the interaction mode between the ruthenium complex and Aß fibrils.


Assuntos
Peptídeos beta-Amiloides/análise , Complexos de Coordenação/química , Rutênio/química , Complexos de Coordenação/síntese química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Agregados Proteicos
12.
Nat Commun ; 11(1): 41, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900396

RESUMO

The development of programmable microscale materials with cell-like functions, dynamics and collective behaviour is an important milestone in systems chemistry, soft matter bioengineering and synthetic protobiology. Here, polymer/nucleotide coacervate micro-droplets are reconfigured into membrane-bounded polyoxometalate coacervate vesicles (PCVs) in the presence of a bio-inspired Ru-based polyoxometalate catalyst to produce synzyme protocells (Ru4PCVs) with catalase-like activity. We exploit the synthetic protocells for the implementation of multi-compartmentalized cell-like models capable of collective synzyme-mediated buoyancy, parallel catalytic processing in individual horseradish peroxidase-containing Ru4PCVs, and chemical signalling in distributed or encapsulated multi-catalytic protocell communities. Our results highlight a new type of catalytic micro-compartment with multi-functional activity and provide a step towards the development of protocell reaction networks.


Assuntos
Células Artificiais/química , Catalase/química , Rutênio/química , Compostos de Tungstênio/química , Catalase/síntese química , Catálise , Peroxidase do Rábano Silvestre/química
13.
Nat Commun ; 11(1): 408, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964865

RESUMO

Biological systems are known to spontaneously adjust the functioning of neurotransmitters, ion channels, and the immune system, being promoted or regulated through allosteric effects or inhibitors, affording non-linear responses to external stimuli. Here we report that an insulated conjugated bimetallopolymer, in which Ru(II) and Pt(II) complexes are mutually connected with insulated conjugations, exhibits phosphorescence in response to CO gas. The net profile corresponds to a sigmoidal response with a dual self-controlling system, where drastic changes were exhibited at two threshold concentrations. The first threshold for activation of the system is triggered by the depolymerization of the non-radiative conjugated polymer to luminescent monomers, while the second one for regulation is triggered by the switch in the rate-determining step of the Ru complex. Such a molecular design with cooperative multiple transition metals would provide routes for the development of higher-ordered artificial molecular systems bearing bioinspired responses with autonomous modulation.


Assuntos
Materiais Biomiméticos/química , Complexos de Coordenação/química , Polímeros/química , Materiais Inteligentes/química , Monóxido de Carbono/análise , Luminescência , Platina/química , Rutênio/química , alfa-Ciclodextrinas/química
14.
Dalton Trans ; 49(4): 972-976, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31894797

RESUMO

An HCBP1 peptide-ruthenium conjugate (Ru-ß-Ala-FQHPSFI) as a potential candidate for targeted therapy of hepatoma was synthesized. Ru-ß-Ala-FQHPSFI shows drastically enhanced cytotoxicity and high selectivity for hepatoma cells versus noncancer liver cells. Raman imaging shows that this peptide-based drug can be taken up well by the hepatoma cells compared with the bare ruthenium complex (Ru) and the opposite sequence peptide-ruthenium conjugate (Ru-ß-Ala-IFSPHQF). This study presents a new strategy for the construction of tumor-targeting metal-based anticancer therapeutics.


Assuntos
Carcinoma Hepatocelular/patologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Neoplasias Hepáticas/patologia , Oligopeptídeos/química , Rutênio/química , Sequência de Aminoácidos , Células Hep G2 , Humanos
15.
Dalton Trans ; 49(4): 1143-1156, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31894801

RESUMO

A series of 2-phenyl and 2-pyridyl tris-benzimidazole ligands was reacted with the [Ru(p-cymene)Cl2]2 dimer to yield the corresponding neutral cyclometallated and cationic organoruthenium(ii) complexes. All of the synthesized compounds were characterized using an array of spectroscopic and analytical techniques, including 1H, 13C nuclear magnetic resonance (NMR), infrared spectroscopy and mass spectrometry. The trinuclear compounds were screened for their cytotoxicy against the MCF-7 breast cancer cell line and the triple negative MDA-MB-231 breast cancer cell line at concentrations of 10 and 20 µM. Overall, the 2-pyridyl ligands 10 and 11, and their corresponding trinuclear complexes [16][PF6]3 and [17][PF6]3, show the most promising activity as these compounds significantly reduce the percentage cell survival of MCF-7 and MDA-MB-231 breast cancer cell lines at the aforementioned fixed concentrations. It was observed that 10 and [16][PF6]3 show potency greater than that of cisplatin against the MCF-7 breast cancer cell line, and [17][PF6]3 shows potency comparable to that of cisplatin against the MCF-7 cell line. Additionally, the synthesized compounds were observed to have relatively low cytotoxicty towards MCF-12A breast epithelial cells and relatively higher selectivity towards MCF-7 breast cancer cells compared to cisplatin.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzimidazóis/química , Quelantes/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Rutênio/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Complexos de Coordenação/síntese química , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular
16.
Dalton Trans ; 49(4): 1207-1219, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31903475

RESUMO

Two types of ruthenium(ii) complexes containing 1,2,4-triazolo[1,5-a]pyrimidines of the general formulas [RuCl2(dmso)3(L)] ((1)-(3)) and [RuCl2(dmso)2(L)2] ((4)-(6)), where L represents 1,2,4-triazolo[1,5-a]pyrimidine (tp for (1)), 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp for (2)), 7-isobutyl-5-methyl-1,2,4-trizolo[1,5-a]pyrimidine (ibmtp for (3)), 5,7-diethyl-1,2,4-triazolo[1,5-a]pyrimidine (detp for (4)), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp for (5)) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp for (6)), have been synthesized and characterized by elemental analysis, infrared, multinuclear magnetic resonance spectroscopic techniques (1H, 13C, and 15N), and X-ray (for (3), (4), and (5)). All these complexes have been thoroughly screened for their in vitro cytotoxicity against melanoma cell lines A375 and Hs294T, indicating cis,cis,cis-[RuCl2(dbtp)2(dmso)2] (5) as the most active representative, in addition to being non-toxic to normal human fibroblasts (NHDF) and not inducing hemolysis of human erythrocytes. In order to develop an intravenous formulation for (5), liposomes composed of soybean phosphatidylcholine (SPC), cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) were prepared and subsequently characterized. (5)-Loaded liposomes, with spherical morphology, assessed by transmission electron microscope (TEM), exhibited satisfactory encapsulation efficiency and stability. In in vitro experiments, PEG-modified (5)-loaded liposomes were more effective (10-fold) than free (5) for growth inhibition of both human melanoma cell lines. Furthermore, such an approach resulted in the reduction of cancer cell viability that was even 10-fold greater than that observed for free cisplatin.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Lipossomos/química , Melanoma/patologia , Nanoestruturas/química , Pirimidinas/química , Rutênio/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Cápsulas , Linhagem Celular Tumoral , Complexos de Coordenação/administração & dosagem , Humanos , Interações Hidrofóbicas e Hidrofílicas , Triazóis/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-31925629

RESUMO

Worldwide there is a large research investment in developing solar fuel systems as clean and sustainable sources of energy. The fundamental mechanisms of natural photosynthesis can provide a source of inspiration for these studies. Photosynthetic reaction center (RC) proteins capture and convert light energy into chemical energy that is ultimately used to drive oxygenic water-splitting and carbon fixation. For the light energy to be used, the RC communicates with other donor/acceptor components via a sophisticated electron transfer scheme that includes electron transfer reactions between soluble and membrane bound proteins. Herein, we reengineer an inherent interprotein electron transfer pathway in a natural photosynthetic system to make it photocatalytic for aqueous H2 production. The native electron shuttle protein ferredoxin (Fd) is used as a scaffold for binding of a ruthenium photosensitizer and H2 catalytic function is imparted to its partner protein, ferredoxin-NADP+-reductase (FNR), by attachment of cobaloxime molecules. We find that this 2-protein biohybrid system produces H2 in aqueous solutions via light-induced interprotein electron transfer reactions (TON > 2500 H2/FNR), providing insight about using native protein-protein interactions as a method for fuel generation.


Assuntos
Hidrogênio/metabolismo , Luz , Anabaena/enzimologia , Catálise/efeitos da radiação , Domínio Catalítico , Transporte de Elétrons/efeitos da radiação , Ferredoxina-NADP Redutase/química , Ferredoxina-NADP Redutase/metabolismo , NADP/metabolismo , Concentração Osmolar , Fármacos Fotossensibilizantes/química , Rutênio/química , Fatores de Tempo
18.
Molecules ; 25(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936496

RESUMO

Since the discovery of the anticancer potential of ruthenium-based complexes, several species were reported as promising candidates for the treatment of breast cancer, which accounts for the greatest number of new cases in women every year worldwide. Among these ruthenium complexes, species containing bioactive ligand(s) have attracted increasing attention due to their potential multitargeting properties, leading to anticancer drug candidates with a broader range of cellular targets/modes of action. This review of the literature aims at providing an overview of the rationally designed ruthenium-based complexes that have been reported to date for which ligands were carefully selected for the treatment of hormone receptor positive breast cancers (estrogen receptor (ER+) or progesterone receptor (PR+)). In addition, this brief survey highlights some of the most successful examples of ruthenium complexes reported for the treatment of triple negative breast cancer (TNBC), a highly aggressive type of cancer, regardless of if their ligands are known to have the ability to achieve a specific biological function.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Rutênio/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Feminino , Humanos , Ligantes , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Rutênio/uso terapêutico , Neoplasias de Mama Triplo Negativas/genética
19.
Molecules ; 25(2)2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31963860

RESUMO

The Pictet-Spengler reaction (P-S) is one of the most direct, efficient, and variable synthetic method for the construction of privileged pharmacophores such as tetrahydro-isoquinolines (THIQs), tetrahydro-ß-carbolines (THBCs), and polyheterocyclic frameworks. In the lustro (five-year period) following its centenary birthday, the P-S reaction did not exit the stage but it came up again on limelight with new features. This review focuses on the interesting results achieved in this period (2011-2015), analyzing the versatility of this reaction. Classic P-S was reported in the total synthesis of complex alkaloids, in combination with chiral catalysts as well as for the generation of libraries of compounds in medicinal chemistry. The P-S has been used also in tandem reactions, with the sequences including ring closing metathesis, isomerization, Michael addition, and Gold- or Brønsted acid-catalyzed N-acyliminium cyclization. Moreover, the combination of P-S reaction with Ugi multicomponent reaction has been exploited for the construction of highly complex polycyclic architectures in few steps and high yields. The P-S reaction has also been successfully employed in solid-phase synthesis, affording products with different structures, including peptidomimetics, synthetic heterocycles, and natural compounds. Finally, the enzymatic version of P-S has been reported for biosynthesis, biotransformations, and bioconjugations.


Assuntos
Modelos Moleculares , Alcaloides/síntese química , Alcaloides/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Ciclização , Rutênio/química
20.
Eur J Med Chem ; 188: 112030, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31945643

RESUMO

Ruthenium-based complexes currently attract great attention as they hold promise to replace platinum-based drugs as a first line cancer treatment. Whereas ruthenium arene complexes are some of the most studied species for their potential anticancer properties, other types of ruthenium complexes have been overlooked for this purpose. Here, we report the synthesis and characterization of Ru(II) cyclopentadienyl (Cp), Ru(II) cyclooctadienyl (COD) and Ru(III) complexes bearing anastrozole or letrozole ligands, third-generation aromatase inhibitors currently used for the treatment of estrogen receptor positive (ER +) breast cancer. Among these complexes, Ru(II)Cp 2 was the only one that displayed a high stability in DMSO and in cell culture media and consequently, the only complex for which the in vitro and in vivo biological activities were investigated. Unlike anastrozole alone, complex 2 was considerably cytotoxic in vitro (IC50 values < 1 µM) in human ER + breast cancer (T47D and MCF7), triple negative breast cancer (TNBC) (MBA-MB-231), and in adrenocortical carcinoma (H295R) cells. Theoretical (docking simulation) and experimental (aromatase catalytic activity) studies suggested that an interaction between 2 and the aromatase enzyme was not likely to occur and that the bulkiness of the PPh3 ligands could be an important factor preventing the complex to reach the active site of the enzyme. Exposure of zebrafish embryos to complex 2 at concentrations around its in vitro cytotoxicity IC50 value (0.1-1 µM) did not lead to noticeable signs of toxicity over 96 h, making it a suitable candidate for further in vivo investigations. This study confirms the potential of Ru(II)Cp complexes for breast cancer therapy, more specifically against TNBCs that are usually not responsive to currently used chemotherapeutic agents.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Complexos de Coordenação/farmacologia , Ciclopentanos/farmacologia , Rutênio/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ciclopentanos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Rutênio/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Peixe-Zebra/embriologia
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