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1.
J Chem Phys ; 151(14): 144712, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615232

RESUMO

Electrogenerated chemiluminescence (ECL) is a promising technique for low concentration molecular detection. To improve the detection limit, plasmonic nanoparticles have been proposed as signal boosting antennas to amplify ECL. Previous ensemble studies have hinted that spectral overlap between the nanoparticle antenna and the ECL emitter may play a role in signal enhancement. Ensemble spectroscopy, however, cannot resolve heterogeneities arising from colloidal nanoparticle size and shape distributions, leading to an incomplete picture of the impact of spectral overlap. Here, we isolate the effect of nanoparticle-emitter spectral overlap for a model ECL system, coreaction of tris(2,2'-bipyridyl)dichlororuthenium(ii) hexahydrate and tripropylamine, at the single-particle level while minimizing other factors influencing ECL intensities. We found a 10-fold enhancement of ECL among 952 gold nanoparticles. This signal enhancement is attributed exclusively to spectral overlap between the nanoparticle and the emitter. Our study provides new mechanistic insight into plasmonic enhancement of ECL, creating opportunities for low concentration ECL sensing.


Assuntos
Nanopartículas Metálicas/química , Compostos Organometálicos/química , Propilaminas/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro/química , Ouro/efeitos da radiação , Luz , Luminescência , Medições Luminescentes/métodos , Nanopartículas Metálicas/efeitos da radiação , Compostos Organometálicos/efeitos da radiação
2.
Chem Commun (Camb) ; 55(77): 11551-11554, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31490470

RESUMO

A novel ratiometric electrochemiluminescence (ECL)-electrochemical (EC) hybrid biosensor with a high accuracy and reproducibility was fabricated for the ultrasensitive detection of miRNA-133a. With the help of a DNA tetrahedron nanostructure and hybridization chain reaction dual amplification strategy, the detection limit of 12.17 aM for miRNA-133a was obtained.


Assuntos
Técnicas Biossensoriais/métodos , DNA/química , MicroRNAs/análise , Nanoestruturas/química , 2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/química , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas , Corantes Fluorescentes/química , Humanos , Limite de Detecção , Medições Luminescentes , Azul de Metileno/química , Técnicas de Amplificação de Ácido Nucleico , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Compostos Organometálicos/química
3.
Chem Commun (Camb) ; 55(77): 11619-11622, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31501844

RESUMO

Mesoporous organosilica nanoparticles (PHT-PMO) have been prepared from an octa-triethoxysilylated Zn phthalocyanine precursor. These PHT-PMO nanoparticles had no dark toxicity but high phototoxicity when irradiated at 650 nm, and remarkable near-infrared phototoxicity when excited at 760 and 810 nm. The PHT-PMO were then aminated to promote electrostatic complexation with siRNA. Transfection experiments were performed upon NIR irradiation and photochemical internalization was very efficient, leading to 65% luciferase extinction in MCF-7 cancer cells expressing stable luciferase.


Assuntos
Indóis/química , Nanopartículas/química , Compostos Organometálicos/química , Fotoquimioterapia/métodos , RNA Interferente Pequeno/química , Silanos/química , Sobrevivência Celular , Cetrimônio/química , Humanos , Raios Infravermelhos , Luciferases/genética , Células MCF-7 , Processos Fotoquímicos , Porosidade , RNA Interferente Pequeno/metabolismo , Eletricidade Estática , Propriedades de Superfície
4.
Chemistry ; 25(55): 12820-12829, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31411775

RESUMO

An inorganic sandwich molecule, Na[Co(C2 B9 H11 )2 ], able to produce vesicles through self-assembly and known to produce strong dihydrogen-bond interactions with amine groups is capable of interacting with proteins. This dual non-bonding ability of Na[Co(C2 B9 H11 )2 ] is what makes this molecule unique: it can be firmly anchored to a protein surface and is capable of extending over it. To prove this, the widely available bovine serum albumin (BSA), which has many pendant amino groups in its structure, has been taken as the model protein. It has been found that around 100 molecules of Na[Co(C2 B9 H11 )2 ] preserve the native structure of BSA, while endorsing it with a significantly increased stability with respect to chemical- and thermal-induced denaturation due to efficient encapsulation. The advantages of this encapsulation technique are two-fold; the first is its simplicity as it relies on the anchoring capacity of Na[Co(C2 B9 H11 )2 ] to the surface of the protein through the amine-containing residues and the second is its self-assembling capacity allowing it to spread across the surface. The dense shield of protection offered by Na[Co(C2 B9 H11 )2 ] has been demonstrated by the inhibition of BSA pseudo-esterase activity, which indicates that the inorganic corset around BSA protects its reactive surface residues, thereby preventing their acetylation.


Assuntos
Boranos/química , Compostos Organometálicos/química , Soroalbumina Bovina/metabolismo , Animais , Desnaturação Proteica , Soroalbumina Bovina/química
5.
Inorg Chem ; 58(17): 11294-11299, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31411862

RESUMO

The first two examples of polyoxopalladates(II) (POPs) containing tetravalent metal ion guests, [MO8Pd12(PO4)8]12- (M = SnIV, PbIV), have been prepared and structurally characterized in the solid state, solution, and gas phase. The interactions of the metal ion guests and the palladium-oxo shell were studied by theoretical calculations. The POPs were shown to possess anticancer activity by causing oxidative stress inducing caspase activation and consecutive apoptosis of leukemic cells.


Assuntos
Antineoplásicos/farmacologia , Metais Pesados/química , Compostos Organometálicos/farmacologia , Polímeros/química , Antineoplásicos/síntese química , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Íons/química , Modelos Moleculares , Compostos Organometálicos/síntese química , Compostos Organometálicos/química
6.
Inorg Chem ; 58(17): 11782-11792, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31433630

RESUMO

Reproduction of the dominant vector of Zika and dengue diseases, Aedes aegypti mosquito, is controlled by an active heterodimer complex composed of the 20-hydroxyecdysone receptor (EcR) and ultraspiracle protein. Although A. aegypti EcR shares the structural and functional organization with other nuclear receptors, its C-terminus has an additional long F domain (AaFEcR). Recently, we showed that the full length AaFEcR is intrinsically disordered with the ability to specifically bind divalent metal ions. Here, we describe the details of the exhaustive structural and thermodynamic properties of Zn2+- and Cu2+-complexes with the AaFEcR domain, based on peptide models of its two putative metal binding sites (Ac-HGPHPHPHG-NH2 and Ac-QQLTPNQQQHQQQHSQLQQVHANGS-NH2). Unexpectedly, only in the presence of increasing concentrations of Cu2+ ions, the Ac-HGPHPHPHG-NH2 peptide gained a metal ion-induced poly-l-proline type II helical structure, which is unique for members of the family of nuclear receptors.


Assuntos
Aedes/efeitos dos fármacos , Antivirais/farmacologia , Cobre/farmacologia , Compostos Organometálicos/farmacologia , Peptídeos/farmacologia , Receptores de Esteroides/antagonistas & inibidores , Animais , Antivirais/química , Sítios de Ligação/efeitos dos fármacos , Cobre/química , Dengue/tratamento farmacológico , Dengue/metabolismo , Estrutura Molecular , Compostos Organometálicos/química , Peptídeos/química , Receptores de Esteroides/metabolismo , Termodinâmica , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/metabolismo
7.
Inorg Chem ; 58(17): 11649-11655, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31436093

RESUMO

A new mixed-valent dicopper complex [5] was generated from ligand exchange by dissolving a bis(CH3CN) precursor [3] in acetone. Introduction of a water molecule in place of an acetonitrile ligand was evidenced by base titration and the presence of a remaining coordinated CH3CN by IR, 19F NMR, and theoretical methods. The proposed structure (CH3CN-Cu-(SR)-Cu-OH2) was successfully DFT-optimized and the calculated parameters are in agreement with the experimental data. [5] has a unique temperature-dependence EPR behavior, with a localized valence from 10 to 120 K that undergoes delocalized at room temperature. The electrochemical signatures are in the line of the other aquo parent [2] and sensibly different from the rest of the series. Similar to the case of [2], [5] was finally capable of single turnover N2O reduction at room temperature. N2 was detected by GC-MS, and the redox character was confirmed by EPR and ESI-MS. Kinetic data indicate a reaction rate order close to 1 and a rate 10 times faster compared to [2]. [5] is thus the second example of that kind and highlights not only the main role of the Cu-OH2 motif, but also that the adjacent Cu-X partner (X = OTf- in [2] and CH3CN in [5]) is a new actor in the casting to establish structure/activity correlations.


Assuntos
Cobre/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos Organometálicos/farmacologia , Oxirredutases/antagonistas & inibidores , Peptídeos/farmacologia , Cobre/química , Teoria da Densidade Funcional , Técnicas Eletroquímicas , Inibidores Enzimáticos/química , Estrutura Molecular , Compostos Organometálicos/química , Oxirredutases/metabolismo , Peptídeos/química
8.
Top Curr Chem (Cham) ; 377(5): 23, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463700

RESUMO

Since the pioneering independent reports of Akiyama and Terada, the use of chiral phosphoric acids (CPAs) and derivatives as a versatile tool for asymmetric synthesis with good reactivity, regioselectivity, diastereoselectivity and enantioselectivity has emerged, forming an important part of the implementation of asymmetric counteranion-directed catalysis reported to date. In these achievements, the combination of metals with CPAs has enabled various catalytic modes beyond the scope of typical acid catalysis, such as relay catalysis, ion-pairing catalysis, and binary acid catalysis. The first-row transition metals (Sc-Zn) are considered to be sustainable transition metals and have received a great deal of attention. These naturally abundant metals display excellent Lewis acidity and function as powerful redox catalysts in synthesis involving both one and two-electron transfers. Hence, in this chapter, we summarize recent advances in the development of asymmetric reactions using a combination of first-row transition metals and CPAs. Furthermore, we provide a detailed discussion of the mechanisms involved in order to understand the interaction of the metal/phosphate and the origins of the asymmetric control of the transformations.


Assuntos
Alcenos/síntese química , Compostos Organometálicos/química , Ácidos Fosfóricos/química , Elementos de Transição/química , Alcenos/química , Catálise , Estrutura Molecular
9.
Food Chem ; 301: 125254, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398672

RESUMO

Researches based on metal complexes of plant-derived phenolic acids have attracted much attention due to their beneficial applications in the development of functional food products, dietary supplements and pharmacology. Binding of phenolic acids with serum proteins greatly influences their pharmacological properties. In this context, interactions of a naturally occurring phenolic acid, sinapic acid (SA) and its Cu2+ complex with a model transport protein, bovine serum albumin (BSA), have been explored by means of different spectroscopic and theoretical tools. Spectroscopic studies revealed that the interaction of SA and its Cu2+ complex with BSA occurred through quenching of intrinsic fluorescence of BSA. Site-specific experimental and docking studies were performed to predict the binding site. The geometies of bound Cu2+ and interacting residues of protein were predicted from a solution dynamics study. Interestingly, the complexation of SA with Cu2+ enhanced the antioxidant activity of SA.


Assuntos
Cobre/química , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Simulação de Acoplamento Molecular , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Sítios de Ligação , Bovinos , Ligação Proteica , Conformação Proteica , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Termodinâmica
10.
Chemphyschem ; 20(17): 2204-2209, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31298452

RESUMO

The efficiency of MRI contrast agents depends on the relaxation rate enhancement that they can induce at imaging fields. It is well known that, at these fields, large relaxation rates are obtained by binding of gadolinium(III) ions to large molecules. By the same token, the interaction of the gadolinium(III) complexes with macromolecules that are found in biological tissues can be responsible for an increase of the relaxation rate with respect to the value observed in liquids. We investigate here the relaxation enhancement of gadoteridol (Gd-HP-DO3A) in crosslinked hyaluronic acid, taken as model tissue, using fast field-cycling relaxometry. The analysis of the relaxation profiles as a function of the magnetic fields indicates that a sizable increase in the relaxation rates is due to a modest interaction of the contrast agent with the hydrogel and to the slower mobility of the water molecules outside the first-coordination sphere of the gadolinium(III) ion.


Assuntos
Meios de Contraste/química , Compostos Heterocíclicos/química , Ácido Hialurônico/química , Imagem por Ressonância Magnética/métodos , Modelos Biológicos , Compostos Organometálicos/química , Gadolínio/química , Água/química
11.
Chemistry ; 25(55): 12810-12819, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31298434

RESUMO

The Hg-C bond of MeHgCl, a ubiquitous environmental toxicant, is notoriously inert and exceedingly difficult to cleave. The cleavage of the Hg-C bond of MeHgCl at low temperature, therefore, is of significant importance for human health. Among various bis(imidazole)-2-selones Ln Se (n=1-4, or 6), the three-spacer L3 Se shows extraordinarily high reactivity in the degradation of various mercury alkyls including MeHgCl because of its unique ability to coordinate through κ2 -fashion, in which both the Se atoms simultaneously attack the Hg center of mercury alkyls for facile Hg-C bond cleavage. It has the highest softness (σ) parameter and the lowest HOMO(Ln Se)-LUMO(MeHgX) energy gap and, thus, L3 Se is the most reactive among Ln Se towards MeHgX (X=Cl or I). L3 Se is highly efficient, more than L1 Se, in restoring the activity of antioxidant enzyme glutathione reductase (GR) that is completely inhibited by MeHgCl; 80 % GR activity is recovered by L3 Se relative to 50 % by L1 Se. It shows an excellent cytoprotective effect in liver cells against MeHgCl-induced oxidative stress by protecting vital antioxidant enzymes from inhibition caused by MeHgCl and, thus, does not allow to increase the intracellular reactive oxygen species (ROS) levels. Furthermore, it protects the mitochondrial membrane potential (ΔΨm ) from perturbation by MeHgCl. Major Hg-responsive genes analyses demonstrate that L3 Se plays a significant role in MeHg+ detoxification in liver cells.


Assuntos
Antioxidantes/farmacologia , Glutationa Redutase/metabolismo , Substâncias Perigosas/análise , Mercúrio/análise , Mercúrio/toxicidade , Compostos Organometálicos/química , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Antioxidantes/química , Citoproteção , Glutationa Redutase/química , Substâncias Perigosas/química , Humanos , Mercúrio/química , Espécies Reativas de Oxigênio/química , Selênio/análise
12.
Photochem Photobiol Sci ; 18(8): 2012-2022, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282525

RESUMO

Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Irídio/farmacologia , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Rutênio/química , Rutênio/farmacologia , Oxigênio Singlete/análise , Oxigênio Singlete/metabolismo , Células Tumorais Cultivadas
13.
Chem Commun (Camb) ; 55(53): 7631-7634, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31197298

RESUMO

Despite their attractive properties, internal targeted alpha therapies using 223/224Ra are limited to bone-seeking applications. As there is no suitable chelator available, the search for new carriers to stably bind Ra2+ and to connect it to biological target molecules is necessary. Polyoxopalladates represent a class of compounds where Ra2+ can be easily introduced into the Pd-POM core during a facile one-pot preparation. Due to the formation of a protein corona, the connection to other targeting (bio)macromolecules is possible.


Assuntos
Compostos Organometálicos/química , Paládio/química , Polímeros/química , Compostos Radiofarmacêuticos/química , Rádio (Elemento)/química
14.
Food Chem ; 292: 98-105, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054698

RESUMO

Accurate and early diagnosis of mycotoxin is particularly significant to the food and agricultural product safety. In the present work, a sensitive and effective monitoring method for zearalenone (ZEN) was exploited based on a novel self-enhanced electrochemiluminescence (ECL) aptasensor. The self-enhanced lumonophore was compounded by electrostatically combining amine-functionalized Ru(bpy)32+-doped silica nanoparticles (NH2-Ru@SiO2 NPs) and nitrogen doped graphene quantum dots (NGQDs) together. Since the emitter and co-reactant simultaneously existed in the same nanoparticle, shortened electron-transfer distance and decreased energy loss was obtained. Therefore, self-enhanced ECL aptasensor based on the novel complex expressed the widest linear range of 10 fg mL-1-10 ng mL-1 and the lowest detection limit of 1 fg mL-1 for ZEN detection. More importantly, ZEN produced during the mildew process of corn flour was monitored by the developed aptasensor, which exhibited superior determination and potential application in real samples.


Assuntos
Aptâmeros de Nucleotídeos/química , Medições Luminescentes/métodos , Nanopartículas/química , Zea mays/metabolismo , Zearalenona/análise , 2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/química , Farinha/análise , Grafite/química , Limite de Detecção , Compostos Organometálicos/química , Pontos Quânticos/química , Reprodutibilidade dos Testes , Dióxido de Silício/química , Zea mays/química
15.
Environ Pollut ; 251: 530-537, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108285

RESUMO

Antifouling booster biocides are chemicals used in protective paints to tackle the adhesion of fouling organisms to maritime artificial structures. However, they are also known to exert toxic effects on non-target organisms. Recent research developments have highlighted the potential use of engineered micro/nanomaterials (EMNMs) as carriers of antifouling booster biocides in order to control their release and to reduce the harmful effects on living biota. In the present study, we sought to assess the toxicity of two commercially-available booster biocides: (zinc pyrithione (ZnPT) and copper pyrithione (CuPT)); three unloaded engineered micro/nanomaterials (EMNMs); layered double hydroxides (LDH), silica nanocapsules (SiNC), polyurea microcapsules (PU); , and six novel EMNMs (loaded with each of the two biocides). The exposure tests were conducted on the larval stage (nauplii) of the brine shrimp Artemia salina and on two embryonic developmental stages of the European purple sea urchin Paracentrotus lividus. The findings indicate that the unloaded LDH and PU (i.e. both biocide-free EMNMs) have non/low toxic effects on both species. The unloaded SiNC, in contrast, exerted a mild toxic effect on the A. salina nauplii and P. lividus embryos. The free biocides presented different toxicity values, with ZnPT being more toxic than CuPT in the P. lividus assays. LDH-based pyrithiones demonstrated lower toxicity compared to the free forms of the state-of-the-art compounds, and constitute good candidates in terms of their antifouling efficacy.


Assuntos
Artemia/efeitos dos fármacos , Desinfetantes/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Nanoestruturas/toxicidade , Paracentrotus/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Desinfetantes/química , Larva/efeitos dos fármacos , Dose Letal Mediana , Nanoestruturas/química , Compostos Organometálicos/química , Compostos Organometálicos/toxicidade , Pintura/análise , Tamanho da Partícula , Piridinas/química , Piridinas/toxicidade , Testes de Toxicidade
17.
Mol Med Rep ; 19(6): 5142-5152, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059081

RESUMO

The purpose of the present study was to investigate the effect of carbon monoxide (CO) released from CO­releasing molecule 2 (CORM­2) on mice with acute pancreatitis (AP). To perform the investigation, a mouse AP model was established using caerulein. The mice were treated with or without CORM­2. The survival rate of the mice in the different groups was analyzed, and serum amylase and lipase levels were measured to assess the degree of pancreatic injury. The severity of AP was also evaluated by histological examination, and histopathological scoring of the pancreatic damage was performed. Pancreatic cell apoptosis was analyzed using a terminal deoxynucleotidyl­transferase­mediated dUTP nick end labelling assay. The function of the lung and liver was also assessed in the present study. Furthermore, the role of CORM­2 on oxidative stress, intercellular adhesion molecule 1 (ICAM­1) and vascular cell adhesion molecule 1 (VCAM­1) expression, pro­inflammatory cytokine production, and nuclear factor (NF)­κB activation in the pancreas of AP mice was determined. The results demonstrated that CORM­2 reduced the mortality, pancreatic damage, and lung and liver injury of AP mice. CORM­2 administration also reduced systemic and localized inflammatory cell factors. Furthermore, treatment with CORM­2 inhibited the expression of ICAM­1 and VCAM­1, and the activation of NF­κB and phosphorylated inhibitor of NF­κB subunit α, in the pancreas of AP mice. These results indicated that CO released from CORM­2 exerted protective effects on AP mice, and the beneficial effects were likely due to inhibition of NF­κB pathway activation.


Assuntos
Monóxido de Carbono/metabolismo , Compostos Organometálicos/farmacologia , Pancreatite/prevenção & controle , Doença Aguda , Amilases/sangue , Animais , Ceruletídeo/toxicidade , Citocinas/metabolismo , Modelos Animais de Doenças , Molécula 1 de Adesão Intercelular/metabolismo , Lipase/sangue , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Compostos Organometálicos/química , Compostos Organometálicos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/induzido quimicamente , Pancreatite/patologia , Peroxidase/metabolismo
18.
Eur J Med Chem ; 175: 269-286, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31096151

RESUMO

Organometallic complexes have widely been used for the treatment of various diseases viz., malaria, arthritis, syphilis, pernicious anemia, tuberculosis and particular in cancers. Recent decades have witnessed an upsurging interest in the application of organometallic compounds to treat various phenotypes of cancers with multiple etiologies. The unique and exceptional properties of organometallic compounds, intermediate between classical inorganic and organic materials provide new insight in the progress of inorganic medicinal chemistry. Herein, we have selectively focused on various organometallic sandwich and half-sandwich complexes of ruthenium (Ru), titanium (Ti), gold (Au) and iron (Fe) exhibiting promising activity towards a panel of cancer cell lines and resistant cancer cell lines. These complexes exhibit novel mechanisms of drug action through incorporation of outer-sphere recognition of molecular targets and controlled activation features based on ligand substitution along with monometallic and heterometallic redox processes. Furthermore, they are usually found to be uncharged or neutral possessing metals in a low oxidation state, exhibit kinetic stability, relative lipophilicity and are amenable to a host of various chemical transformations. This review mainly sheds light on the successful advancement of organometallic complexes as anticancer drug aspirants in relation to their versatile structural chemistry and innovative mechanisms of action targeting nucleic acids, several enzymes viz; thioredoxin reductases (Thrx), EGFR, transferrin, cathepsin B, topoisomerases etc.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Compostos Organometálicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Catepsina B/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , DNA Topoisomerases/efeitos dos fármacos , Receptores ErbB/efeitos dos fármacos , Ouro/química , Humanos , Neoplasias/patologia , Ácidos Nucleicos/efeitos dos fármacos , Compostos Organometálicos/química , Compostos Organometálicos/uso terapêutico , Rutênio/química , Tiorredoxina Dissulfeto Redutase/efeitos dos fármacos , Titânio/química , Transferrina/efeitos dos fármacos
19.
Cancer Sci ; 110(7): 2090-2099, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31111571

RESUMO

Inflammation plays an essential role in the development and progression of most cancers. Chemokine C-C motif chemokine 2 (CCL2) and its receptor C-C chemokine receptor type 2 (CCR2) constitute a key signaling axis in inflammation that has recently attracted much interest on the basis of evidence showing its association with cancer progression. Propagermanium (3-oxygermylpropionic acid polymer) is an organogermanium compound that is given for the treatment of hepatitis B in Japan and which inhibits the CCL2-CCR2 signaling pathway. Herein, we review the importance of the CCL2-CCR2 axis as a target in cancer treatment as shown by studies in mice and humans with pharmacological agents including propagermanium.


Assuntos
Antineoplásicos/farmacologia , Quimiocina CCL2/metabolismo , Neoplasias/tratamento farmacológico , Compostos Organometálicos/farmacologia , Receptores CCR2/metabolismo , Animais , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Japão , Camundongos , Neoplasias/imunologia , Compostos Organometálicos/química , Compostos Organometálicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico
20.
Chem Commun (Camb) ; 55(60): 8764-8767, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31139806

RESUMO

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


Assuntos
DNA/química , Substâncias Intercalantes/química , Compostos Organometálicos/química , Fenantrenos/química , Adutos de DNA/síntese química , Guanina/química , Substâncias Intercalantes/efeitos da radiação , Ligantes , Luz , Conformação de Ácido Nucleico , Compostos Organometálicos/efeitos da radiação , Fenantrenos/efeitos da radiação , Fenantrolinas/química , Fenantrolinas/efeitos da radiação , Rutênio/química
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