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1.
Chemistry ; 26(40): 8676-8688, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32452579

RESUMO

Resistance to chemotherapy is a current clinical problem, especially in the treatment of microbial infections and cancer. One strategy to overcome this is to make new derivatives of existing drugs by conjugation to organometallic fragments, either by an appropriate linker, or by direct coordination of the drug to a metal. We illustrate this with examples of conjugated organometallic metallocene sandwich and half-sandwich complexes, RuII and OsII arene, and RhIII and IrIII cyclopentadienyl half-sandwich complexes. Ferrocene conjugates are particularly promising. The ferrocene-chloroquine conjugate ferroquine is in clinical trials for malaria treatment, and a ferrocene-tamoxifen derivative (a ferrocifen) seems likely to enter anticancer trails soon. Several other examples illustrate that organometallic conjugation can restore the activity of drugs to which resistance has developed.


Assuntos
Aminoquinolinas/química , Antimaláricos/uso terapêutico , Cloroquina/farmacologia , Complexos de Coordenação/química , Compostos Ferrosos/química , Malária/tratamento farmacológico , Metalocenos/química , Compostos Organometálicos/química , Compostos de Rutênio/farmacologia , Antimaláricos/farmacologia , Cloroquina/química , Complexos de Coordenação/uso terapêutico , Humanos , Estrutura Molecular , Compostos de Rutênio/síntese química
2.
Am J Trop Med Hyg ; 103(1): 378-393, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32314694

RESUMO

Malaria volunteer infection studies (VISs) accelerate new drug and vaccine development. In the induced blood-stage malaria (IBSM) model, volunteers are inoculated with erythrocytes infected with Plasmodium falciparum. Observations of elevated liver enzymes in the IBSM model with new chemical entities (NCEs) promoted an analysis of available data. Data were reviewed from eight IBSM studies of seven different NCEs, plus two studies with the registered antimalarial piperaquine conducted between June 2013 and January 2017 at QIMR Berghofer, Brisbane, Australia. Alanine aminotransferase (ALT) was elevated (> 2.5 times the upper limit of normal [×ULN]) in 20/114 (17.5%) participants. Of these, 8.9% (10/114) had moderate increases (> 2.5-5 × ULN), noted in seven studies of six different NCEs ± piperaquine or piperaquine alone, and 8.9% (10/114) had severe elevations (> 5 × ULN), occurring in six studies of six different NCEs ± piperaquine. Aspartate aminotransferase (AST) was elevated (> 2.5 × ULN) in 11.4% (13/114) of participants, across six of the 10 studies. Bilirubin was > 2 × ULN in one participant. Published data from other VIS models, using sporozoite inoculation by systemic administration or mosquito feeding, also showed moderate/severe liver enzyme elevations. In conclusion, liver enzyme elevations in IBSM studies are most likely multifactorial and could be caused by the model conditions, that is, malaria infection/parasite density and/or effective parasite clearance, or by participant-specific risk factors, acetaminophen administration, or direct hepatotoxicity of the test drug. We make recommendations that may mitigate the risk of liver enzyme elevations in future VISs and propose measures to assist their interpretation, should they occur.


Assuntos
Alanina Transaminase/metabolismo , Antimaláricos/efeitos adversos , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Voluntários Saudáveis , Malária Falciparum/tratamento farmacológico , Parasitemia/tratamento farmacológico , Acrilamidas/efeitos adversos , Adamantano/efeitos adversos , Adamantano/análogos & derivados , Adulto , Aminopiridinas/efeitos adversos , Aminoquinolinas/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Transfusão de Eritrócitos , Eritrócitos/parasitologia , Feminino , Compostos Ferrosos/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Indóis/efeitos adversos , Isoquinolinas/efeitos adversos , Masculino , Metalocenos/efeitos adversos , Peróxidos/efeitos adversos , Piperazinas/efeitos adversos , Plasmodium falciparum , Primaquina/efeitos adversos , Pirimidinas/efeitos adversos , Quinolinas/efeitos adversos , Compostos de Espiro/efeitos adversos , Sulfonas/efeitos adversos , Triazóis/efeitos adversos , Adulto Jovem
3.
PLoS One ; 15(3): e0228740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214347

RESUMO

Parasitic diseases are a neglected and serious problem, especially in underdeveloped countries. Among the major parasitic diseases, Leishmaniasis figures as an urgent challenge due to its high incidence and severity. At the same time, the indiscriminate use of antibiotics by the population is increasing together with resistance to medicines. To address this problem, new antibiotic-like molecules that directly kill or inhibit the growth of microorganisms are necessary, where antimicrobial peptides (AMPs) can be of great help. In this work, the ferrocene molecule, one active compound with low levels of in vivo toxicity, was coupled to the N-terminus of the RP1 peptide (derived from the human chemokine CXCL4), aiming to evaluate how this change modifies the structure, biological activity, and toxicity of the peptide. The peptide and the conjugate were synthesized using the solid phase peptide synthesis (SPPS). Circular dichroism assays in PBS showed that the RP1 peptide and its conjugate had a typical spectrum for disordered structures. The Fc-RP1 presented anti-amastigote activity against Leishmania amazonensis (IC50 = 0.25 µmol L-1). In comparison with amphotericin B, a second-line drug approved for leishmaniasis treatment, (IC50 = 0.63 µmol L-1), Fc-RP1 was more active and showed a 2.5-fold higher selectivity index. The RP1 peptide presented a MIC of 4.3 µmol L-1 against S. agalactiae, whilst Fc-RP1 was four times more active (MIC = 0.96 µmol L-1), indicating that ferrocene improved the antimicrobial activity against Gram-positive bacteria. The Fc-RP1 peptide also decreased the minimum inhibitory concentration (MIC) in the assays against E. faecalis (MIC = 7.9 µmol L-1), E. coli (MIC = 3.9 µmol L-1) and S. aureus (MIC = 3.9 µmol L-1). The cytotoxicity of the compounds was tested against HaCaT cells, and no significant activity at the highest concentration tested (500 µg. mL-1) was observed, showing the high potential of this new compound as a possible new drug. The coupling of ferrocene also increased the vesicle permeabilization of the peptide, showing a direct relation between high peptide concentration and high carboxyfluorescein release, which indicates the action mechanism by pore formation on the vesicles. Several studies have shown that ferrocene destabilizes cell membranes through lipid peroxidation, leading to cell lysis. It is noteworthy that the Fc-RP1 peptide synthesized here is a prototype of a bioconjugation strategy, but it still is a compound with great biological activity against neglected and fish diseases.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Compostos Ferrosos/química , Metalocenos/química , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/toxicidade , Bactérias/efeitos dos fármacos , Leishmania/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Permeabilidade
4.
Bioelectrochemistry ; 132: 107412, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31889632

RESUMO

The synthesis of a series of methyl 2-alkyl-5-aryl-4-ferrocenoylpyrrolidine-2-carboxylates has been achieved by [3 + 2] dipolar cycloaddition of azomethine ylides to acryloylferrocene. The electrochemical properties of novel products were examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). These techniques revealed the quasi-reversible one-electron oxidation process. The DNA-binding capacity of all the products was also studied using CV and DPV, and significant interactions between synthesized compounds and nucleic acid, mostly of the electrostatic type, were disclosed. DFT calculations and molecular docking tests were carried out to gain a more exhaustive insight into the interactions of the obtained products with nucleic acid. A detailed characterization of the new compounds was performed by IR, NMR and elemental analyses, followed by single-crystal X-ray diffraction experiments for two representatives.


Assuntos
DNA/metabolismo , Técnicas Eletroquímicas/métodos , Compostos Ferrosos/metabolismo , Metalocenos/metabolismo , Cristalografia por Raios X , Teoria da Densidade Funcional , Compostos Ferrosos/química , Espectroscopia de Ressonância Magnética , Metalocenos/química , Estrutura Molecular , Oxirredução , Espectrofotometria Infravermelho
5.
Mater Sci Eng C Mater Biol Appl ; 108: 110371, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924004

RESUMO

The objective of this paper is to demonstrate the potential of nanostructured polypyrrole formed by template free as platform for amperometric detection of DNA. The nanowires of polypyrrole (nw-PPy) are formed through electrochemical polymerization and chemically modified by electrochemical oxidation of ethylene diamine or dendrimers PAMAM to obtain aminated surface. The DNA probe and ferrocenyl group, as redox reporter, were covalently linked to the surface of nw-PPy. The chemical structure of nanostructured platform was characterized through SEM, FT-IR and XPS and the electrochemical properties through cyclic voltammetry and electrochemical impedance spectroscopy (EIS). We show that the properties of nw-PPy such as, hydrophilic character and large surface area have large effect on the electronic properties. Thus, the electrochemical performance is increased compared to others nanomaterials considering the obtained value of the rate of electron transfer of 18 s-1. These properties allow enhanced DNA sensing where detection limit of 0.36 atomolar without any amplification step. The biosensor can be applied in detection of genomic DNA of Mycobacterium tuberculosis and the mutated one which present the resistance to rifampicin and large selectivity was demonstrated. We believe that nw-PPy modified with redox marker is a promising platform for electrochemical biosensors and can be applied for various diagnosis prospects.


Assuntos
Técnicas Biossensoriais , DNA Bacteriano/análise , Técnicas Eletroquímicas/métodos , Mycobacterium tuberculosis/genética , Nanoestruturas/química , Polímeros/química , Pirróis/química , Dendrímeros/química , Eletrólitos/química , Compostos Ferrosos/química , Ouro/química , Cinética , Metalocenos/química , Mycobacterium tuberculosis/isolamento & purificação , Nanoestruturas/ultraestrutura , Nanofios/química , Nanofios/ultraestrutura , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Dalton Trans ; 49(4): 1181-1190, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31897458

RESUMO

A new chiral organometallic nucleoside analogue containing ruthenocene is reported, in which alkylthymine and alkylhydroxyl groups are attached in adjacent positions on one cyclopentadienyl ring. The synthetic procedures for this metallocene derivative and two control compounds are described, along with their characterisation by cyclic voltammetry and X-ray crystallography. Their biological activities in a human pancreatic cancer cell line (MIA-Pa-Ca-2) were significantly lower than those of three previously reported analogous ferrocene compounds, indicating that the choice of metallocene metal atom (Fe or Ru) plays a pivotal role in determining the anticancer properties of these nucleoside analogues, which in turn suggests a different mode of action from that of a conventional nucleoside analogue.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Metalocenos/química , Metalocenos/farmacologia , Nucleosídeos/química , Linhagem Celular Tumoral , Eletroquímica , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Conformação Molecular
7.
ACS Appl Mater Interfaces ; 12(5): 5624-5632, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31918542

RESUMO

The aggregation of hydrophobic photosensitizers limits the therapeutic effect of photodynamic therapy (PDT). Improving the hydrophilicity of photosensitizers can reduce their aggregation for enhancing PDT. Herein, a nanosystem (TPFcNP) is developed by a hydrophobic photosensitizer 5,10,15,20-tetrakis(4-methacryloyloxyphenyl)porphyrin (TMPP) containing multiple carbon-carbon double bonds and a ferrocene-containing amphiphilic block copolymer (PEG-b-PMAEFc), which catalyzes hydrogen peroxide (H2O2) to produce hydroxyl radicals (•OH) in a tumor microenvironment by the Fenton reaction. The •OH could catalyze the addition reaction between the carbon-carbon double bonds of TMPP and overexpressed water-soluble glutathione (GSH) in tumor cells, which greatly improves the hydrophilicity of photosensitizers and reduces their aggregation. Experiments in vitro and in vivo have proved that this strategy significantly enhances the therapeutic efficacy of PDT. Catalyzing intracellular reactions in situ by making use of the tumor microenvironment will open up a new opportunity to solve the aggregation of materials in the tumor for cancer treatment.


Assuntos
Peróxido de Hidrogênio/química , Radical Hidroxila/química , Fármacos Fotossensibilizantes/química , Animais , Catálise , Linhagem Celular Tumoral , Feminino , Compostos Ferrosos/química , Glutationa/química , Glutationa/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Radical Hidroxila/metabolismo , Metalocenos/química , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/química , Porfirinas/química , Transplante Heterólogo
8.
Molecules ; 25(3)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973221

RESUMO

The discovery of ferrocene is often associated with the rapid growth of organometallic chemistry. Dendrimers are highly branched macromolecules that can be functionalized at will at all levels of their structure. The functionalization of dendrimers with ferrocene derivatives can be carried out easily as terminal functions on the surface, but also at the core, or at one or several layers inside the structure. This review will focus on phosphorhydrazone dendrimers functionalized with ferrocene derivatives, on the surface, at the core, at all layers or within a single layer inside the structure. The first part will describe the synthesis; the second part will concern the electrochemical properties; and the last part will give several examples concerning catalysis, with complexes of ferrocenyl phosphines used as terminal functions of dendrimers.


Assuntos
Dendrímeros/síntese química , Eletroquímica , Compostos Ferrosos/síntese química , Hidrazonas/síntese química , Metalocenos/síntese química , Catálise , Dendrímeros/química , Compostos Ferrosos/química , Hidrazonas/química , Metalocenos/química , Oxirredução
9.
Anal Chim Acta ; 1099: 52-59, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-31986277

RESUMO

Structuring of noble metal nanoparticles on transition metal dichalcogenide nanosheets induces significantly enhanced electronic, optical, and catalytic functions. However, the synthesis of multifunctional hybrids is always time-consuming and involves multiple steps. Herein, a ternary Au nanoparticle-ferrocene-WS2 nanosheet (AFW) composite has been prepared by a facile one-step sonochemical approach. Stripped WS2 nanosheets were functionalized with ferrocene monocarboxylic acid (FMC) and gold nanoparticles (AuNPs) by making use of the strong coordinative interaction of carboxyl groups with tungsten atoms. The AuNPs decorating the WS2 nanosheet not only increase the water solubility of WS2 nanosheet and surface area of the modified electrode, but also act as electron transport bridges to aid the tunneling of electrons from the small redox molecule, FMC, through the space to the electrode on which they are mounted. Furthermore, the ternary AFW nanocomposite could effectively avoid the leaching of FMC from the nanocomposite matrix and provided a suitable environment for the immobilized biomolecules. Combining the immune magnetic beads technology and the AFW nanocomposite with aforementioned advantages, a high-performance electrochemical immunosensor was successfully developed using carbohydrate antigen 72-4 (CA72-4) as a model analyte. A linear relationship in the range of 2-50 U/L for the detection of CA72-4 was found with a low detection limit of 0.6 U/L. In addition, the biosensor showed excellent performance in selectivity, stability, and reproducibility. Thus, this work not only proposes a facile avenue for preparing a 2D WS2 nanocomposite with multifunctional properties but also opens up a new method to extend the application of WS2-based materials in biological sensing.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Técnicas Biossensoriais , Técnicas Eletroquímicas , Imunoensaio , Ultrassom , Antígenos Glicosídicos Associados a Tumores/imunologia , Compostos Ferrosos/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Metalocenos/química , Nanocompostos/química , Sulfetos/química , Compostos de Tungstênio/química
10.
J Antibiot (Tokyo) ; 73(5): 299-308, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31988484

RESUMO

The swift spread of infections caused by drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has quickly become a worldwide concern as infections spread from healthcare settings to the wider community. While ferrocenyl chalcones, which are chalcone derivatives with antimicrobial activity, have gained attention from researchers, further study is needed to assess their cytotoxicity. Ten newly developed chalcones, in which ring A was replaced with a ferrocenyl moiety and ring B contained increasing alkyl chain lengths from 1 to 10 carbons, were assessed. Using twofold broth microdilution, the minimum inhibitory concentration (MIC) of five of the ten compounds were lower against Gram-positive organisms (MICs from 0.008 mg ml-1 to 0.063 mg ml-1) than Gram-negative organisms (MICs = 0.125 mg ml-1). These novel ferrocenyl chalcone compounds were effective against three types of clinically isolated drug-resistant S. aureus, including an MRSA, and against other non-resistant clinically isolated and laboratory-adapted Gram-positive bacteria. The same compounds inhibited growth in non-resistant bacteria by potentially obstructing cellular respiration in Gram-positive bacteria. Images obtained through scanning electron microscopy revealed fully lysed bacterial cells once exposed to a selected compound that showed activity. The results indicate that these newly developed compounds could be important antimicrobial agents in the treatment of infections from clinically resistant bacteria.


Assuntos
Antibacterianos/farmacologia , Chalconas/farmacologia , Compostos Ferrosos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Metalocenos/química , Antibacterianos/síntese química , Antibacterianos/química , Chalconas/síntese química , Chalconas/química , Farmacorresistência Bacteriana , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Relação Estrutura-Atividade
11.
Biochim Biophys Acta Proteins Proteom ; 1868(2): 140335, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785381

RESUMO

Pyranose oxidase (POx) catalyzes the oxidation of d-glucose to 2-ketoglucose with concurrent reduction of oxygen to H2O2. POx from Trametes ochracea (ToPOx) is known to react with alternative electron acceptors including 1,4-benzoquinone (1,4-BQ), 2,6-dichlorophenol indophenol (DCPIP), and the ferrocenium ion. In this study, enzyme variants with improved electron acceptor turnover and reduced oxygen turnover were characterized as potential anode biocatalysts. Pre-steady-state kinetics of the oxidative half-reaction of ToPOx variants T166R, Q448H, L545C, and L547R with these alternative electron acceptors were evaluated using stopped-flow spectrophotometry. Higher kinetic constants were observed as compared to the wild-type ToPOx for some of the variants. Subsequently, the variants were immobilized on glassy carbon electrodes. Cyclic voltammetry measurements were performed to measure the electrochemical responses of these variants with glucose as substrate in the presence of 1,4-BQ, DCPIP, or ferrocene methanol as redox mediators. High catalytic efficiencies (Imaxapp/KMapp) compared to the wild-type POx proved the potential of these variants for future bioelectrocatalytic applications, in biosensors or biofuel cells. Among the variants, L545C showed the most desirable properties as determined kinetically and electrochemically.


Assuntos
Desidrogenases de Carboidrato/metabolismo , Técnicas Eletroquímicas/métodos , 2,6-Dicloroindofenol/química , Benzoquinonas/química , Biocatálise , Desidrogenases de Carboidrato/química , Desidrogenases de Carboidrato/genética , Domínio Catalítico , Eletrodos , Compostos Ferrosos/química , Glucose/química , Glucose/metabolismo , Cinética , Metalocenos/química , Mutagênese Sítio-Dirigida , Oxirredução , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Trametes/enzimologia
12.
Chemistry ; 26(6): 1286-1291, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31725178

RESUMO

Three sets of 7-deazaadenine and cytosine nucleosides and nucleoside triphosphates bearing either unsubstituted ferrocene, octamethylferrocene and ferrocenecarboxamide linked through an alkyne tether to position 7 or 5, respectively, were designed and synthesized. The modified dNFcX TPs were good substrates for KOD XL DNA polymerase in primer extension and were used for enzymatic synthesis of redox-labelled DNA probes. Square-wave voltammetry showed that the octamethylferrocene oxidation potential was shifted to lower values, whilst the ferrocenecarboxamide was shifted to higher potentials, as compared to ferrocene. Tailed PEX products containing different ratios of Fc-labelled A (dAFc ) and FcPa-labelled C (dCFcPa ) were synthesized and hybridized with capture oligonucleotides immobilized on gold electrodes to study the electrochemistry of the redox-labelled DNA. Clearly distinguishable, fully orthogonal and ratiometric peaks were observed for the dAFc and dCFcPa bases in DNA, demonstrating their potential for use in redox coding of nucleobases and for the direct electrochemical measurement of the relative ratio of nucleobases in an unknown sequence of DNA.


Assuntos
DNA/química , Compostos Ferrosos/química , Metalocenos/química , Nucleotídeos/química , Coloração e Rotulagem/métodos , Citidina Trifosfato/química , DNA/metabolismo , Sondas de DNA/síntese química , Sondas de DNA/química , DNA Polimerase Dirigida por DNA/metabolismo , Técnicas Eletroquímicas , Oxirredução , Especificidade por Substrato
13.
Chemistry ; 26(1): 139-142, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31680317

RESUMO

Cyclic naphthalene diimides (cNDIs), with a ferrocene moiety (cFNDs) and different linker lengths between the ferrocene and cNDI moieties, were designed and synthesized as redox-active, tetraplex-DNA ligands. Intramolecular stacking was observed between ferrocene and the NDI planes, which could affect the binding properties for G-quadruplexes. Interestingly, the circular dichroism spectrum of one of these compounds clearly shows new Cotton effects around 320-380 and 240 nm, which can be considered a direct evidence of intramolecular stacking of ferrocene and the NDI. Regarding recognition of hybrid G-quadruplexes, the less rigid structures (longer linkers) show higher binding affinity (106 m-1 order of magnitude). All new compounds show higher selectivity for G4 during electrochemical detection than noncyclic FND derivatives, which further identifies the redox-active potentiality of the cFNDs. Two of the three compounds tested even show preferential inhibition of cell growth in cancer cells over normal cells in a low concentration range, highlighting the potential for bioapplications of these cFNDs.


Assuntos
Compostos Ferrosos/química , Quadruplex G , Imidas/química , Metalocenos/química , Naftalenos/química , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Células HeLa , Humanos , Imidas/farmacologia , Ligantes , Naftalenos/farmacologia , Oxirredução , Telômero/química
14.
Anal Chim Acta ; 1094: 18-25, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761044

RESUMO

A competitive electrochemical aptasensor based on a cDNA-ferrocene/MXene probe is used to detect the breast cancer marker Mucin1 (MUC1). MXene (Ti3C2) nanosheets with excellent electrical conductivity and large specific surface area are selected as carriers for aptamer probes. The ferrocene-labeled complementary DNA (cDNA-Fc) is first bound on the surface of MXene to form a cDNA-Fc/MXene probe. Then, the MUC1 aptamer is fixed to the electrode by Au-S bonds. The sensing electrode is named Apt/Au/GCE. After the probe is complementary to the aptamer, a cDNA-Fc/MXene/Apt/Au/GCE aptasensor is fabricated. When the aptasensor is used for detection of MUC1, a competitive process happens between the cDNA-ferrocene/MXene probe and MUC1, which makes cDNA-Fc/MXene probe detach from the sensing electrode, resulting in a decrease in electrical signal. The difference in the corresponding peak current before and after the competition can be used to indicate the quantitative change in bound MUC1. The proposed competitive electrochemical aptasensor gives a wide linear range of 1.0 pM-10 µM and a low detection limit of 0.33 pM (S/N = 3), which is promising for clinical diagnosis.


Assuntos
Aptâmeros de Nucleotídeos/química , Biomarcadores Tumorais/sangue , DNA Complementar/química , Compostos Ferrosos/química , Metalocenos/química , Mucina-1/sangue , Titânio/química , Aptâmeros de Nucleotídeos/genética , Técnicas Biossensoriais/métodos , DNA Complementar/genética , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Limite de Detecção , Hibridização de Ácido Nucleico , Reprodutibilidade dos Testes
15.
Chem Commun (Camb) ; 56(6): 976-979, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31859315

RESUMO

By using multivalent manganese oxides microflowers (MnOx MFs) as prominent a coreaction accelerator in luminol/dissolved oxygen system, and by combining these with DNA nanostructures for efficient immobilization of the electrochemiluminescence (ECL) quencher doxorubicin-ferrocenecarboxylic acid (Dox-FcCOOH), an ultrasensitive biosensing platform was constructed to conduct a microRNA assay in tumour cells.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , Compostos de Manganês/química , MicroRNAs/análise , Óxidos/química , DNA/química , Doxorrubicina/química , Compostos Ferrosos/química , Metalocenos/química , Nanoestruturas/química
16.
Eur J Med Chem ; 187: 111963, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865015

RESUMO

The tropical disease malaria is responsible for more than 400,000 deaths annually, especially in Southeast Asia and Africa. Although the number of malaria cases is declining, there still is an urgent need for novel antimalarial agents. The emergence of hybrid antimalarial agents and the precedence set by the antimalarial drug ferroquine (FQ) prompted us to design new ferrocene-containing quinoline structures. Herein, we report the efficient synthesis of three different series of ferrocene-quinoline conjugates and a class of ferrocene-containing heterotricycles in good to high yields. For all twenty novel ferrocenyl derivatives, electrochemical properties were investigated using cyclic voltammetry and antiplasmodium evaluation against a chloroquine-susceptible NF54 strain of the human malaria parasite Plasmodium falciparum was conducted, pointing to three compounds showing submicromolar potency. Subsequently, cytotoxicity assays against a Chinese Hamster Ovarian cell line and evaluation against a chloroquine-resistant strain of Plasmodium falciparum for these three compounds revealed selective and promising antiplasmodium activity.


Assuntos
Antimaláricos/farmacologia , Desenho de Fármacos , Técnicas Eletroquímicas , Compostos Ferrosos/farmacologia , Malária/tratamento farmacológico , Metalocenos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/farmacologia , Antimaláricos/síntese química , Antimaláricos/química , Relação Dose-Resposta a Droga , Compostos Ferrosos/química , Humanos , Metalocenos/química , Modelos Moleculares , Estrutura Molecular , Testes de Sensibilidade Parasitária , Quinolinas/química , Relação Estrutura-Atividade
17.
Eur J Med Chem ; 185: 111791, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669852

RESUMO

Hybrid molecules have the potential to enhance the efficacy against both drug-sensitive and drug-resistant organisms, and Ferroquine, a ferrocene hybrid, has demonstrated great potency in clinical trials against both drug-sensitive and drug-resistant malaria. Accordingly, hybridization of ferrocene with other antimalarial pharmacophores represents a promising strategy to develop novel antimalarial candidates. This work attempts to systematically review the recent study of ferrocene hybrids in the design and development of antimalarial agents, and the structure-activity relationship (SAR) is also discussed to provide an insight for rational design of more effective antibacterial candidates.


Assuntos
Antimaláricos/farmacologia , Compostos Ferrosos/farmacologia , Malária/tratamento farmacológico , Metalocenos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Artemisininas/química , Artemisininas/farmacologia , Compostos Ferrosos/química , Humanos , Metalocenos/química , Estrutura Molecular , Testes de Sensibilidade Parasitária , Peróxidos/química , Peróxidos/farmacologia , Quinolinas/química , Quinolinas/farmacologia
18.
Biosens Bioelectron ; 148: 111795, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31665673

RESUMO

In this work, a high-efficiency electrochemiluminescence (ECL) ternary system was constructed for ultrasensitive assay of insulin based on hollow porous graphitic carbon nitride (HP-C3N4) as novel luminophore, S2O82- as coreactant and tri-metallic AuPtAg as coreaction accelerator. Specifically, in comparison with C3N4-based bulk nanomaterials, the as-prepared HP-C3N4 exhibits high luminous efficiency though decreased inner filter effect and minimized inactive ECL emitter. Noteworthy, tri-metallic AuPtAg, possessing the superiority of Au, Pt and Ag, was first used as coreaction accelerator to significantly enhance ECL intensity of HP-C3N4 and S2O82-. As a consequence, with the resultant ECL ternary (HP-C3N4/S2O82-/AuPtAg) system as aptasensing platform, a high-intense initial ECL signal was achieved. Subsequently, ferrocene-labeled quenching probe (Fc-HP2) as ECL quencher was used to quench the initial signal and achieve the low-background noise. Eventually, in the presence of insulin, the target-induced triple-helix molecular switch and Nb.BbvCI-assisted DNA walker amplification were executed to recover a strong ECL signal by releasing Fc-HP2 from the electrode surface. As expected, the constructed aptasensor presents an excellent sensitivity and selectivity for detecting insulin range from 0.05 pg mL-1 to 100 ng mL-1 with a detection limit of 17 fg mL-1. This work provides a new avenue for developing highly efficient HP-C3N4 based ECL ternary system as well as ultrasensitive ECL aptasensors for bioanalysis.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Grafite/química , Insulina/sangue , Substâncias Luminescentes/química , Compostos de Nitrogênio/química , Técnicas Eletroquímicas/métodos , Compostos Ferrosos/química , Ouro/química , Humanos , Insulina/análise , Limite de Detecção , Medições Luminescentes/métodos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Metalocenos/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Técnicas de Amplificação de Ácido Nucleico/métodos , Platina/química , Porosidade , Prata/química
19.
ACS Appl Mater Interfaces ; 11(49): 46112-46123, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31722522

RESUMO

We report a chemo/starvation/chemodynamic trimodal combination therapy to combat multidrug-resistant (MDR) tumors by developing a ferrocene-containing nanovesicle (FcNV), which encapsulates glucose oxidase (GOx) in the hydrophilic core and coordinates cisplatin (Pt) in the hydrophobic layer (GOx&Pt@FcNV). Contrasting with other reported multimodal combination therapies, the new nanodrug (GOx&Pt@FcNV) relies on cascade reactions to drastically increase the overall effectiveness against MDR tumors. Specifically, Pt blocks deoxyribonucleic acid replication and activates hydrogen peroxide (H2O2) generation for chemotherapy; GOx consumes glucose to produce H2O2 and gluconic acid for starvation therapy; and all H2O2 products are catalyzed by ferrous ions decomposed from ferrocene to generate the highly toxic hydroxyl radicals (•OH) for chemodynamic therapy. The in vitro studies reveal that GOx&Pt@FcNV exhibits a highly efficient killing effect against various MDR tumor cells. The in vivo studies of double-tumor-bearing nude mice demonstrate that the tumor inhibitory rates (TIRs) of GOx&Pt@FcNV against cisplatin-resistant A549/DDP are 8.1 times and 3.3 times higher than those of Pt and Pt@FcNV, respectively; they are also 8.6 times and 4.3 times higher than Pt and Pt@FcNV against adriamycin-resistant MCF-7/ADR, respectively. This nanodrug with endogenous stimuli-activated cascade reactions offers a reference for the design of effective trimodal combination therapies to combat MDR tumors.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glucose Oxidase/química , Radical Hidroxila/química , Neoplasias/tratamento farmacológico , Animais , Técnicas Biossensoriais , Cisplatino/química , Cisplatino/farmacologia , Terapia Combinada , Replicação do DNA/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Compostos Ferrosos/química , Glucose/metabolismo , Glucose Oxidase/farmacologia , Humanos , Peróxido de Hidrogênio/química , Ferro/metabolismo , Células MCF-7 , Metalocenos/química , Camundongos , Neoplasias/patologia , Inanição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Phys Chem Chem Phys ; 21(44): 24572-24583, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31663551

RESUMO

In this work, poly(N,N'-dimethylaminoethylmethacrylate-co-N-isopropylacrylamide) copolymer films were polymerized on the surface of Au electrodes with a facile one-step method, and Au nanoclusters (AuNCs) and tetraphenylethene (TPE) were synchronously embedded in the films, designated as P(DMA-co-NIPA)/AuNCs/TPE. Ferrocene dicarboxylic acid (FDA), an electroactive probe in solution displayed inverse pH- and SO42--sensitive on-off cyclic voltammetric (CV) behaviors at the film electrodes. The electrocatalytic oxidation of nicotinamide adenine dinucleotide (NADH) mediated by FDA in solution could substantially amplify the CV response difference between the on and off states. Moreover, the two fluorescence emission (FL) signals from the TPE constituent at 450 nm and AuNCs component at 660 nm in the films also demonstrated SO42-- and pH-sensitive behaviors. Based on the aforementioned results, a 4-input/9-output biomolecular logic circuit was constructed with pH, Na2SO4, FDA and NADH as the inputs, and the CV signals and the FL responses at 450 and 660 nm at different levels as the outputs. Additionally, some functional non-Boolean devices were elaborately designed on an identical platform, including a 1-to-2 decoder, a 2-to-1 encoder, a 1-to-2 demultiplexer and different types of keypad locks. This work combines copolymer films, bioelectrocatalysis, and fluorescence together so that more complicated biocomputing systems could be established. This work may pave a new way to develop advanced and sophisticated biocomputing logic circuits and functional devices in the future.


Assuntos
Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , NAD/química , Polímeros/química , Estilbenos/química , Benzoatos/química , Eletrodos , Compostos Ferrosos/química , Ouro/química , Concentração de Íons de Hidrogênio , Metalocenos , Oxirredução , Espectrometria de Fluorescência , Sulfatos/química
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