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1.
J Colloid Interface Sci ; 667: 450-459, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38643742

RESUMO

Single-atom catalysts (SACs) have attracted extensive attention in the field of catalysis due to their excellent catalytic ability and enhanced atomic utilization, but the multi-mode single-atom nanozymes for biosensors remain a challenging issue. In this work, iron-doped carbon dots (Fe CDs) were loaded onto the edges and pores of Mo SACs with nanoflower morphology; accordingly, a composite material Fe CDs/Mo SACs was prepared successfully, which improves the catalytic performance and develops a fluorescence mode without changing the original morphology. The steady-state kinetic data indicates that the material prepared have better affinity for substrates and faster reaction rates under optimized conditions. The specific kinetic parameters Km and Vmax were calculated as 0.39 mM and 7.502×10-7 M·s-1 respectively. The excellent peroxidase-like activity of Fe CDs/Mo SACs allows H2O2 to decompose into •OH, which in turn oxidizes colorless o-phenylenediamine (OPD) to yellow 2,3-diaminophenazine (DAP). At the same time, the fluorescence signal of Fe CDs/Mo SACs quenches obviously by DAP at 460 nm through internal filtration effect (IFE), while the characteristic fluorescence response of DAP gradually increases at 590 nm. Based on this sensing mechanism, a sensitive and accurate dual-mode (colorimetric and ratiometric fluorescent) sensor was constructed to detect H2O2 and uric acid, and the rate of recovery and linearity were acceptable for the detection of UA in human serum and urine samples. This method provides a new strategy for rapid and sensitive detection of UA, and also broadens the development of SACs in the field of biosensors.


Assuntos
Carbono , Peróxido de Hidrogênio , Ferro , Molibdênio , Pontos Quânticos , Ácido Úrico , Ácido Úrico/análise , Ácido Úrico/urina , Ácido Úrico/sangue , Ácido Úrico/química , Molibdênio/química , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Carbono/química , Ferro/química , Pontos Quânticos/química , Catálise , Humanos , Técnicas Biossensoriais , Limite de Detecção , Tamanho da Partícula , Nanoestruturas/química , Propriedades de Superfície , Fenilenodiaminas/química
2.
Mikrochim Acta ; 191(5): 282, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652326

RESUMO

A novel dual-mode fluorometric and colorimetric sensing platform is reported for determining glutathione S-transferase (GST) by utilizing polyethyleneimine-capped silver nanoclusters (PEI-AgNCs) and cobalt-manganese oxide nanosheets (CoMn-ONSs) with oxidase-like activity. Abundant active oxygen species (O2•-) can be produced through the CoMn-ONSs interacting with dissolved oxygen. Afterward, the pink oxDPD was generated through the oxidation of colorless N,N-diethyl-p-phenylenediamine (DPD) by O2•-, and two absorption peaks at 510 and 551 nm could be observed. Simultaneously, oxDPD could quench the fluorescence of PEI-AgNCs at 504 nm via the inner filter effect (IFE). However, in the presence of glutathione (GSH), GSH prevents the oxidation of DPD due to the reducibility of GSH, leading to the absorbance decrease at 510 and 551 nm. Furthermore, the fluorescence at 504 nm was restored due to the quenching effect of oxDPD on decreased PEI-AgNCs. Under the catalysis of GST, GSH and1-chloro-2,4-dinitrobenzo (CDNB) conjugate to generate an adduct, initiating the occurrence of the oxidation of the chromogenic substrate DPD, thereby inducing a distinct colorimetric response again and the significant quenching of PEI-AgNCs. The detection limits for GST determination were 0.04 and 0.21 U/L for fluorometric and colorimetric modes, respectively. The sensing platform illustrated reliable applicability in detecting GST in real samples.


Assuntos
Cobalto , Colorimetria , Glutationa Transferase , Compostos de Manganês , Nanopartículas Metálicas , Óxidos , Polietilenoimina , Prata , Polietilenoimina/química , Prata/química , Cobalto/química , Óxidos/química , Compostos de Manganês/química , Nanopartículas Metálicas/química , Colorimetria/métodos , Glutationa Transferase/metabolismo , Glutationa Transferase/química , Limite de Detecção , Oxirredutases/química , Oxirredutases/metabolismo , Humanos , Glutationa/química , Oxirredução , Técnicas Biossensoriais/métodos , Fenilenodiaminas/química , Nanoestruturas/química
3.
Dalton Trans ; 53(14): 6311-6322, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38487871

RESUMO

While platinum(II)-based drugs continue to be employed in cancer treatments, the escalating occurrence of severe side effects has spurred researchers to explore novel sources for potential therapeutic agents. Notably, cobalt(III) has emerged as a subject of considerable interest due to its ubiquitous role in human physiology. Several studies investigating the anticancer effects of Salphen complexes derived from cobalt(III) have unveiled intriguing antiproliferative properties. In a bid to enhance our understanding of this class of compounds, we synthesized and characterized two novel half Salphen cobalt(III) complexes. Both compounds exhibited notable stability, even in the presence of physiologically relevant concentrations of glutathione. The application of spectroscopic and computational methodologies unravelled their interactions with duplex and G4-DNAs, suggesting an external binding affinity for these structures, with preliminary indications of selectivity trends. Importantly, antiproliferative assays conducted on 3D cultured SW-1353 cancer cells unveiled a compelling anticancer activity at low micromolar concentrations, underscoring the potential therapeutic efficacy of this novel class of cobalt(III) complexes.


Assuntos
Antineoplásicos , Complexos de Coordenação , Humanos , Complexos de Coordenação/química , Cobalto/farmacologia , Cobalto/química , Fenilenodiaminas/química , DNA/química , Antineoplásicos/química
4.
Environ Sci Technol ; 57(14): 5978-5987, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36992570

RESUMO

Rapid urbanization drives increased emission of tire wear particles (TWPs) and the contamination of a transformation product derived from tire antioxidant, termed as N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), with adverse implications for terrestrial ecosystems and human health. However, whether and how 6PPD-Q could be formed during the aging of TWPs in soils remains poorly understood. Here, we examine the accumulation and formation mechanisms of 6PPD-Q during the aging of TWPs in soils. Our results showed that biodegradation predominated the fate of 6PPD-Q in soils, whereas anaerobic flooded conditions were conducive to the 6PPD-Q formation and thus resulted in a ∼3.8-fold higher accumulation of 6PPD-Q in flooded soils than wet soils after aging of 60 days. The 6PPD-Q formation in flooded soils was enhanced by Fe reduction-coupled 6PPD oxidation in the first 30 days, while the transformation of TWP-harbored environmentally persistent free radicals (EPFRs) to superoxide radicals (O2•-) under anaerobic flooded conditions further dominated the formation of 6PPD-Q in the next 30 days. This study provides significant insight into understanding the aging behavior of TWPs and highlights an urgent need to assess the ecological risk of 6PPD-Q in soils.


Assuntos
Benzoquinonas , Fenilenodiaminas , Solo , Áreas Alagadas , Humanos , Anaerobiose , Radicais Livres/química , Ferro/química , Fenilenodiaminas/química , Benzoquinonas/química , Oxirredução , Biodegradação Ambiental , Molhabilidade
5.
Environ Sci Technol ; 57(14): 5621-5632, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36996351

RESUMO

6PPD, a tire rubber antioxidant, poses substantial ecological risks because it can form a highly toxic quinone transformation product (TP), 6PPD-quinone (6PPDQ), during exposure to gas-phase ozone. Important data gaps exist regarding the structures, reaction mechanisms, and environmental occurrence of TPs from 6PPD ozonation. To address these data gaps, gas-phase ozonation of 6PPD was conducted over 24-168 h and ozonation TPs were characterized using high-resolution mass spectrometry. The probable structures were proposed for 23 TPs with 5 subsequently standard-verified. Consistent with prior findings, 6PPDQ (C18H22N2O2) was one of the major TPs in 6PPD ozonation (∼1 to 19% yield). Notably, 6PPDQ was not observed during ozonation of 6QDI (N-(1,3-dimethylbutyl)-N'-phenyl-p-quinonediimine), indicating that 6PPDQ formation does not proceed through 6QDI or associated 6QDI TPs. Other major 6PPD TPs included multiple C18H22N2O and C18H22N2O2 isomers, with presumptive N-oxide, N,N'-dioxide, and orthoquinone structures. Standard-verified TPs were quantified in roadway-impacted environmental samples, with total concentrations of 130 ± 3.2 µg/g in methanol extracts of tire tread wear particles (TWPs), 34 ± 4 µg/g-TWP in aqueous TWP leachates, 2700 ± 1500 ng/L in roadway runoff, and 1900 ± 1200 ng/L in roadway-impacted creeks. These data demonstrate that 6PPD TPs are likely an important and ubiquitous class of contaminants in roadway-impacted environments.


Assuntos
Antioxidantes , Benzoquinonas , Fenilenodiaminas , Borracha , Antioxidantes/química , Ozônio/química , Borracha/química , Água/química , Fenilenodiaminas/química , Benzoquinonas/química
6.
Dalton Trans ; 52(10): 2966-2975, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36444991

RESUMO

DNA G-rich sequences can organize in four-stranded structures called G-quadruplexes (G4s). These motifs are enriched in significant sites within the human genomes, including telomeres and promoters of cancer related genes. For instance, KIT proto-oncogene promoter, associated with diverse cancers, contains three adjacent G4 units, namely Kit2, SP, and Kit1. Aiming at finding new and selective G-quadruplex binders, we have synthesized and characterized five non-charged metal complexes of Pt(II), Pd(II), Ni(II), Cu(II) and Zn(II) of a chlorine substituted Salphen ligand. The crystal structure of the Pt(II) and Pd(II) complexes was determined by XRPD. FRET measurements indicated that Pt(II) and Pd(II) compounds stabilize Kit1 and Kit2 G4s but not SP, telomeric and double stranded DNA. Spectroscopic investigations (UV-Vis, circular dichroism and fluorescence) suggested the Cu(II) complex as the most G4-selective compound. Interestingly, docking simulations indicate that the synthesized compounds fit groove binding pockets of both Kit1 and Kit2 G4s. Moreover, they exhibited dose-dependent cytotoxic activity in MCF-7, HepG2 and HeLa cancer cells.


Assuntos
Antineoplásicos , Complexos de Coordenação , Quadruplex G , Humanos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Antineoplásicos/farmacologia , Fenilenodiaminas/química , Dicroísmo Circular , Telômero
7.
PLoS One ; 16(11): e0260002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780548

RESUMO

Bacterial degradation of xenobiotic compounds is an intense field of research already for decades. Lately, this research is complemented by downstream applications including Next Generation Sequencing (NGS), RT-PCR, qPCR, and RNA-seq. For most of these molecular applications, high-quality RNA is a fundamental necessity. However, during the degradation of aromatic substrates, phenolic or polyphenolic compounds such as polycatechols are formed and interact irreversibly with nucleic acids, making RNA extraction from these sources a major challenge. Therefore, we established a method for total RNA extraction from the aromatic degrading Pseudomonas capeferrum TDA1 based on RNAzol® RT, glycogen and a final cleaning step. It yields a high-quality RNA from cells grown on TDA1 and on phenol compared to standard assays conducted in the study. To our knowledge, this is the first report tackling the problem of polyphenolic compound interference with total RNA isolation in bacteria. It might be considered as a guideline to improve total RNA extraction from other bacterial species.


Assuntos
Meios de Cultura/química , Poliuretanos/química , Pseudomonas/crescimento & desenvolvimento , RNA Bacteriano/isolamento & purificação , Fenol/química , Fenilenodiaminas/química , Pseudomonas/genética , RNA Bacteriano/normas , Xenobióticos/química
8.
Bioorg Chem ; 116: 105355, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34592689

RESUMO

Photodynamic therapy (PDT) is a non-invasive treatment method for tumors by exciting photosensitizers (PS) upon light irradiation to generate cytotoxic reactive oxygen species (ROS). However, the low oxygen concentration near the tumor tissue limits the therapeutic effect of PDT. Herein, we synthesized six chlorin e6 derivatives containing NO-donors to enhance their antitumor activity by synergistic effect of ROS and NO. The results revealed that the new NO-donor containing photosensitizers (PS-NO) exhibited more potent photodynamic activity than chlorin e6, and the introduction of NO donor moieties to chlorin e6 increased the level of NO and ROS in cells. The addition of Ferrostatin-1, a ferroptosis inhibitor, markedly reduced the photodynamic activity of PS-NO as well as the level of NO and ROS in cells. Mechanism studies further showed that PS-NO could reduce intracellular GSH level, inhibit GPX4 activity and promote malondialdehyde (MDA) accumulation upon light irradiation, which suggested the ferroptosis mechanism underlying the PDT effect of PS-NO.


Assuntos
Cicloexilaminas/farmacologia , Fenilenodiaminas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Cicloexilaminas/síntese química , Cicloexilaminas/química , Relação Dose-Resposta a Droga , Ferroptose/efeitos dos fármacos , Células HeLa , Humanos , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Fenilenodiaminas/síntese química , Fenilenodiaminas/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
9.
Molecules ; 26(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070615

RESUMO

Protein kinase CK2 is a highly pleiotropic protein kinase capable of phosphorylating hundreds of protein substrates. It is involved in numerous cellular functions, including cell viability, apoptosis, cell proliferation and survival, angiogenesis, or ER-stress response. As CK2 activity is found perturbed in many pathological states, including cancers, it becomes an attractive target for the pharma. A large number of low-mass ATP-competitive inhibitors have already been developed, the majority of them halogenated. We tested the binding of six series of halogenated heterocyclic ligands derived from the commercially available 4,5-dihalo-benzene-1,2-diamines. These ligand series were selected to enable the separation of the scaffold effect from the hydrophobic interactions attributed directly to the presence of halogen atoms. In silico molecular docking was initially applied to test the capability of each ligand for binding at the ATP-binding site of CK2. HPLC-derived ligand hydrophobicity data are compared with the binding affinity assessed by low-volume differential scanning fluorimetry (nanoDSF). We identified three promising ligand scaffolds, two of which have not yet been described as CK2 inhibitors but may lead to potent CK2 kinase inhibitors. The inhibitory activity against CK2α and toxicity against four reference cell lines have been determined for eight compounds identified as the most promising in nanoDSF assay.


Assuntos
Caseína Quinase II/química , Halogenação , Compostos Heterocíclicos/síntese química , Fenilenodiaminas/química , Trifosfato de Adenosina/química , Domínio Catalítico , Cromatografia Líquida de Alta Pressão/métodos , Fluorometria/métodos , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Simulação de Acoplamento Molecular
10.
Mikrochim Acta ; 188(5): 156, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33825037

RESUMO

A MnO2 nanosheet-assisted ratiometric fluorescence probe based on carbon quantum dots (CQDs) and o-phenylenediamine (OPD) has been developed for the detection of the anticancer drug 6-mercaptopurine (6-MP). CQDs with strong fluorescence are synthesized via the one-step hydrothermal method. MnO2 nanosheets as an oxidase-mimicking nanomaterial directly oxidize OPD into 2,3-diaminophenazine (DAP) which has a fluorescence emission at 570 nm, whereas the fluorescence of CQDs at 445 nm is then reduced by the DAP through the inner filter effect (IFE) under a single excitation wavelength (370 nm). After adding 6-MP, MnO2 nanosheets can be reduced to Mn2+ and lose their oxidase-like property, blocking the IFE with the fluorescence decrease of DAP and fluorescence increase of CQDs. The novel ratiometric fluorescence probe exhibits considerable sensitivity toward 6-MP and linear response is in the 0.46-100.0 µmol L-1 concentration range with the detection limit of 0.14 µmol L-1. Furthermore, the probe shows good selectivity when exposed to a series of interfering other organic and inorganic compounds, and biomolecules and can be applied to the detection for 6-MP in human serum samples and pharmaceutical tablets. Satisfactory recoveries of 6-MP in human serum samples are in the range 96.1-110.9% with the RSD of 1.4 to 3.2%. The amount of 6-MP is successfully estimated as 49.3 mg in pharmaceutical tablet with the RSD of about  2.2%.


Assuntos
Antineoplásicos/sangue , Corantes Fluorescentes/química , Compostos de Manganês/química , Mercaptopurina/sangue , Óxidos/química , Fenilenodiaminas/química , Pontos Quânticos/química , Carbono/química , Humanos , Limite de Detecção , Oxirredução , Espectrometria de Fluorescência
11.
ACS Chem Biol ; 16(10): 1951-1960, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33769035

RESUMO

O-Acetylation is a common naturally occurring modification of carbohydrates and is especially widespread in sialic acids, a family of nine-carbon acidic monosaccharides. O-Acetyl migration within the exocyclic glycerol-like side chain of mono-O-acetylated sialic acid reported previously was from the C7- to C9-hydroxyl group with or without an 8-O-acetyl intermediate, which resulted in an equilibrium that favors the formation of the 9-O-acetyl sialic acid. Herein, we provide direct experimental evidence demonstrating that O-acetyl migration is bidirectional, and the rate of equilibration is influenced predominantly by the pH of the sample. While the O-acetyl group on sialic acids and sialoglycans is stable under mildly acidic conditions (pH < 5, the rate of O-acetyl migration is extremely low), reversible O-acetyl migration is observed readily at neutral pH and becomes more significant when the pH increases to slightly basic. Sialoglycan microarray studies showed that esterase-inactivated porcine torovirus hemagglutinin-esterase bound strongly to sialoglycans containing a more stable 9-N-acetylated sialic acid analog, but these compounds were less resistant to periodate oxidation treatment compared to their 9-O-acetyl counterparts. Together with prior studies, the results support the possible influence of sialic acid O-acetylation and O-acetyl migration to host-microbe interactions and potential application of the more stable synthetic N-acetyl mimics.


Assuntos
Hemaglutininas Virais/metabolismo , Polissacarídeos/metabolismo , Ácidos Siálicos/metabolismo , Proteínas Virais de Fusão/metabolismo , Acetilação , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Hemaglutininas Virais/química , Estrutura Molecular , Oxirredução , Ácido Periódico/química , Fenilenodiaminas/química , Polissacarídeos/análise , Polissacarídeos/química , Ligação Proteica , Ácidos Siálicos/análise , Ácidos Siálicos/química , Torovirus/enzimologia , Proteínas Virais de Fusão/química
12.
Molecules ; 26(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669598

RESUMO

Synthetic arylamines and dietary phytophenolics could inhibit ferroptosis, a recently discovered regulated cell death process. However, no study indicates whether their inhibitory mechanisms are inherently different. Herein, the ferroptosis-inhibitory mechanisms of selected ferrostatin-1 (Fer-1) and two dietary stilbenes (piceatannol and astringin) were compared. Cellular assays suggested that the ferroptosis-inhibitory and electron-transfer potential levels decreased as follows: Fer-1 >> piceatannol > astringin; however, the hydrogen-donating potential had an order different from that observed by the antioxidant experiments and quantum chemistry calculations. Quantum calculations suggested that Fer-1 has a much lower ionization potential than the two stilbenes, and the aromatic N-atoms were surrounded by the largest electron clouds. By comparison, the C4'O-H groups in the two stilbenes exhibited the lowest bond disassociation enthalpies. Finally, the three were found to produce corresponding dimer peaks through ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis. In conclusion, Fer-1 mainly depends on the electron transfer of aromatic N-atoms to construct a redox recycle. However, piceatannol and astringin preferentially donate hydrogen atoms at the 4'-OH position to mediate the conventional antioxidant mechanism that inhibits ferroptosis, and to ultimately form dimers. These results suggest that dietary phytophenols may be safer ferroptosis inhibitors for balancing normal and ferroptotic cells than arylamines with high electron-transfer potential.


Assuntos
Cicloexilaminas/farmacologia , Dieta , Ferroptose/efeitos dos fármacos , Glucosídeos/farmacologia , Fenilenodiaminas/farmacologia , Estilbenos/farmacologia , Animais , Antioxidantes/análise , Óxidos N-Cíclicos/química , Cicloexilaminas/química , Glucosídeos/química , Imidazóis/química , Concentração Inibidora 50 , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Modelos Moleculares , Fenilenodiaminas/química , Piperazinas/farmacologia , Ratos Sprague-Dawley , Eletricidade Estática , Estilbenos/química
13.
ACS Appl Mater Interfaces ; 13(4): 5486-5497, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33491443

RESUMO

Flexible paper-based sensors may be applied in numerous fields, but this requires addressing their limitations related to poor thermal and water resistance, which results in low service life. Herein, we report a paper-based composite sensor composed of carboxylic carbon nanotubes (CCNTs) and poly-m-phenyleneisophthalamide (PMIA), fabricated by a facile papermaking process. The CCNT/PMIA composite sensor exhibits an ability to detect pressures generated by various human movements, attributed to the sensor's conductive network and the characteristic "mud-brick" microstructure. The sensor exhibits the capability to monitor human motions, such as bending of finger joints and elbow joints, speaking, blinking, and smiling, as well as temperature variations in the range of 30-90 °C. Such a capability to sensitively detect pressure can be realized at different applied frequencies, gradient sagittas, and multiple twists with a short response time (104 ms) even after being soaked in water, acid, and alkali solutions. Moreover, the sensor demonstrates excellent mechanical properties and hence can be folded up to 6000 times without failure, can bear 5 kg of load without breaking, and can be cycled 2000 times without energy loss, providing a great possibility for a long sensing life. Additionally, the composite sensor shows exceptional Joule heating performance, which can reach 242 °C in less than 15 s even when powered by a low input voltage (25 V). From the perspective of industrialization, low-cost and large-scale roll-to-roll production of the paper-based sensor can be achieved, with a formed length of thousands of meters, showing great potential for future industrial applications as a wearable smart sensor for detecting pressure and temperature, with the capability of electric heating.


Assuntos
Nanotubos de Carbono/química , Papel , Fenilenodiaminas/química , Ácidos Ftálicos/química , Polímeros/química , Dispositivos Eletrônicos Vestíveis , Técnicas Biossensoriais/instrumentação , Condutividade Elétrica , Humanos , Monitorização Fisiológica/instrumentação , Movimento (Física) , Nanotubos de Carbono/ultraestrutura
14.
Bioorg Chem ; 104: 104235, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32896808

RESUMO

Based on the multi-mechanism antitumor strategy and the regulatory effect of nitric oxide (NO) on histone deacetylases (HDACs), a series of N-acyl-o-phenylenediamine-based HDAC inhibitors equipped with the phenylsulfonylfuroxan module as NO donor was designed, synthesized and biologically evaluated. The in vitro HDAC inhibitory assays revealed that compared with the clinical class I selective HDAC inhibitor MS275, compounds 7c, 7d and 7e possessed similar HDAC inhibitory potency and selective profile, which were confirmed by the results of western blot analysis. The western blot analysis also showed that NO scavenger N-acetyl cysteine (NAC) could weaken the intracellular HDAC inhibitory ability of compound 7c, supporting the HDAC inhibitory effect of NO generated by 7c. It is worth noting that compounds 7c, 7d and 7e exhibited more potent in vitro antiproliferative activities than MS275 against all four tested solid tumor cell lines. The promising in vivo antitumor potency of 7c was demonstrated in a HCT116 xenograft model.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Óxido Nítrico/antagonistas & inibidores , Fenilenodiaminas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Humanos , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Óxido Nítrico/biossíntese , Fenilenodiaminas/síntese química , Fenilenodiaminas/química , Relação Estrutura-Atividade
15.
ACS Appl Mater Interfaces ; 12(39): 43456-43465, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32880166

RESUMO

Cancer deaths are mainly caused by tumor metastases. However, tumor ablation therapies can only target the primary tumor but not inhibit tumor metastasis. Herein, a multifunctional covalent organic framework (COF)-based nanocomposite is designed for synergetic photo-, chemodynamic- and immunotherapies. Specifically, the synthesized COF possesses the ability to produce singlet oxygen under the 650 nm laser irradiation. After being metallized with FeCl3, p-phenylenediamine is polymerized on the surface of COF with Fe3+ as the oxidant. The obtained poly(p-phenylenediamine) can be used for photothermal therapy. Meanwhile, the overexpressed H2O2 in the tumor would be further catalyzed and decomposed into hydroxyl radicals (•OH) by the Fe3+/Fe2+ redox couple via Fenton reaction. Intriguingly, the increase of temperature caused by photothermal therapy can accelerate the production of •OH. Moreover, the tumor-associated antigen induced a robust antitumor immune response and effectively inhibited tumor metastasis in the presence of anti-PD-L1 checkpoint blockade. Such a COF-based multifunctional nanoplatform provides an efficacious treatment strategy for both the primary tumor and tumor metastasis.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanocompostos/química , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Compostos Férricos/química , Compostos Férricos/farmacologia , Radical Hidroxila/análise , Radical Hidroxila/metabolismo , Inibidores de Checkpoint Imunológico/síntese química , Inibidores de Checkpoint Imunológico/química , Imunoterapia , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Camundongos , Tamanho da Partícula , Fenilenodiaminas/química , Fenilenodiaminas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fototerapia , Propriedades de Superfície
16.
Nanotechnology ; 31(44): 445703, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32659751

RESUMO

In this work, a ratiometric fluorescence method based on nanozyme was fabricated to determine L-Cysteine. Taking silkworm feces as a carbon source, together with Fe3+, Fe-doped carbon dots (Fe-CDs) were synthesized through a hydrothermal method. Fe-CDs were able to oxidize the enzyme substrate o-phenylenediamine (OPD) to produce oxidized OPD (Ox-OPD) when H2O2 coexisted with them. Based on the fluorescence property of Fe-CDs and Ox-OPD, a dual-emission system was built. Since L-Cysteine contains reductive thiols that can inhibit the production of Ox-OPD, the addition of L-Cysteine caused a decrease in the fluorescence intensity of Ox-OPD. The results showed that the ratio of fluorescence intensities at 450 and 560 nm (I450/I560) varied linearly with the concentration of L-Cysteine in the range of 0.25-90 µM and the limit of detection is as low as 0.047 µM. Furthermore, using this ratiometric fluorescence system to determine L-Cysteine in serum and tap-water samples, average recoveries were evaluated to reach 98.75%-103.27% with the relative standard deviation of no more than 4.5%. Based on the fluorescence property and nanozyme-like activity, this work provides an inspiration to open a new horizon in using natural carbon source to synthesize CDs and for the application of CDs as a nanozyme.


Assuntos
Carbono/química , Cisteína/análise , Ferro/química , Pontos Quânticos/química , Animais , Bombyx/química , Cisteína/sangue , Oxirredução , Fenilenodiaminas/química , Espectrometria de Fluorescência/métodos , Água/análise
17.
Anal Chem ; 92(13): 9421-9428, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32489092

RESUMO

Histone demethylases (HDMs) are vital players in epigenetic regulation and important targets in cancer treatment, but effective molecular tools for analyzing HDMs activity are still limited. Interestingly, we found that the process of Ag+-triggered oxidation of O-phenylenediamine (OPD) to 2,3-diaminophenazine (OPDox) could be efficiently inhibited by formaldehyde (HCHO), with the decrease of fluorescent and colorimetric signals from OPDox. Accordingly, we developed a novel label-free fluorescent and colorimetric dual-readout assay for HDMs activity based on direct quantitation of HCHO liberated in the demethylation process. On the basis of the excellent performance of the Ag+-OPD-based method for HCHO quantitation, lysine-specific demethylase 1(LSD1) activity was not only successfully detected with a low detection limit of 0.3 nM (fluorescence) and 0.5 nM (colorimetric) but also observed by the naked eye. Moreover, the feasibility of the proposed assay was further expanded to assess the LSD1 activity in cancer cell lysate and its inhibition through a mix-and-readout procedure. This label-free, cost-effective, and highly sensitive dual-readout assay presents a valuable tool for epigenetics research and drug discovery.


Assuntos
Colorimetria/métodos , Fluorometria/métodos , Formaldeído/química , Histona Desmetilases/metabolismo , Fenilenodiaminas/química , Prata/química , Linhagem Celular , Desmetilação , Hepatócitos/citologia , Hepatócitos/metabolismo , Histonas/metabolismo , Humanos , Oxirredução
18.
ACS Appl Mater Interfaces ; 12(26): 29826-29834, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32469497

RESUMO

Fast and facile coating strategies play a key role in surface engineering and functionalization of materials for various applications. Herein, we report a rapid and eco-friendly hair dyeing process for natural gray hair via the formation of metal-phenolic networks (MPNs). MPNs composed of gallic acid display high performance, and the coloration is tunable by varying the metal ion types. MPN-based hair dyeing is tolerant to repeated washing (at least 50 times) with detergent solution without color fading and can be discolored in acidic solution (pH < 2). The mechanism of self-assembled MPNs for hair dyeing is investigated by Raman and UV-vis absorption spectroscopy. Cell studies in vitro and skin toxicity tests in vivo demonstrate the advantages (i.e., biocompatibility and hair regrowth) of MPNs for hair dyeing compared to p-phenylenediamine. The reported strategy for hair dyeing avoids the use of toxic substances present in common hair dyes and has negligible damage to the hair structures and tensile strength.


Assuntos
Tinturas para Cabelo/química , Fenilenodiaminas/química , Ácido Gálico/química , Análise Espectral Raman , Resistência à Tração
19.
J Inorg Biochem ; 207: 111064, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32220825

RESUMO

The DNA-binding of two salphen-like metal complexes of nickel(II) (1) and zinc(II) (2) was investigated in different ionic strength solutions by absorption spectroscopy. The data analysis allowed us to obtain the values of their extrapolated DNA-binding constant in physiological conditions, with DNA-binding strength in the order Ni > Zn, and to give relative weight to the electrostatic and non-electrostatic contributions to their DNA-interaction.


Assuntos
Complexos de Coordenação/química , DNA/química , Níquel/química , Fenilenodiaminas/química , Zinco/química , Concentração Osmolar , Cloreto de Sódio/química , Análise Espectral , Eletricidade Estática
20.
Anal Chim Acta ; 1107: 193-202, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32200894

RESUMO

In this study, a facile one step solvo-thermal procedure has been employed in generating magnetite-silver core-shell nanocomposites (AgNPs@ Fe3O4) with superior peroxidase-like catalytic property than bare magnetic nanoparticles (Fe3O4). The composites were characterized using different techniques such as transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and surface-enhanced infrared absorption spectroscopy (SEIRA). In the presence of hydrogen peroxide, the synthesized composites were able to oxidize the colorless o-phenylenediamine (OPD) to a yellow colour 2, 3-diaminophenazine (DAP) with a better peroxidase-like activity than Fe3O4 alone. The obtained Km value of AgNPs@ Fe3O4 with H2O2 and OPD substrates are 28.0 mM and 2.91 mM respectively. These are substantially lower than previously reported values and indicate the strong binding affinity of the substrates towards AgNPs@ Fe3O4 nanocomposites. Based on the obstruction activity of cysteine on the peroxidase-like catalytic property of the nanocomposites, a sensor was developed for detection of cystein with a limit of detection as low as 87 nM and a wider range of linearity. The sensor also exhibited excellent selectivity against potentially interfering molecules.


Assuntos
Cisteína/análise , Compostos Férricos/química , Nanopartículas de Magnetita/química , Nanocompostos/química , Catálise , Cisteína/química , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredução , Fenilenodiaminas/química , Prata/química , Espectrofotometria Ultravioleta
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