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1.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206424

RESUMO

Determination of the metabolism pathway of xenobiotics undergoing the hepatic pass is a crucial aspect in drug development since the presence of toxic biotransformation products may result in significant side effects during the therapy. In this study, the complete hepatic metabolism pathway of dapoxetine established according to the human liver microsome assay with the use of a high-resolution LC-MS system was described. Eleven biotransformation products of dapoxetine, including eight metabolites not reported in the literature so far, were detected and identified. N-dealkylation, hydroxylation, N-oxidation and dearylation were found to be the main metabolic reactions for the investigated xenobiotic. In silico analysis of toxicity revealed that the reaction of didesmethylation may contribute to the increased carcinogenic potential of dapoxetine metabolites. On the other hand, N-oxidation and aromatic hydroxylation biotransformation reactions possibly lead to the formation of mutagenic compounds.


Assuntos
Benzilaminas , Simulação por Computador , Microssomos Hepáticos/química , Naftalenos , Benzilaminas/química , Benzilaminas/farmacocinética , Biotransformação , Cromatografia Líquida de Alta Pressão , Humanos , Naftalenos/química , Naftalenos/farmacocinética
2.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802742

RESUMO

New anti-inflammatory treatments are needed for CF airway disease. Studies have implicated the endoplasmic reticulum stress transducer inositol requiring enzyme 1α (IRE1α) in CF airway inflammation. The activation of IRE1α promotes activation of its cytoplasmic kinase and RNase, resulting in mRNA splicing of X-box binding protein-1 (XBP-1s), a transcription factor required for cytokine production. We tested whether IRE1α kinase and RNase inhibition decreases cytokine production induced by the exposure of primary cultures of homozygous F508del CF human bronchial epithelia (HBE) to supernatant of mucopurulent material (SMM) from CF airways. We evaluated whether IRE1α expression is increased in freshly isolated and native CF HBE, and couples with increased XBP-1s levels. A FRET assay confirmed binding of the IRE1α kinase and RNase inhibitor, KIRA6, to the IRE1α kinase. F508del HBE cultures were exposed to SMM with or without KIRA6, and we evaluated the mRNA levels of XBP-1s, IL-6, and IL-8, and the secretion of IL-6 and IL-8. IRE1α mRNA levels were up-regulated in freshly isolated CF vs. normal HBE and coupled to increased XBP-1s mRNA levels. SMM increased XBP-1s, IL-6, and IL-8 mRNA levels and up-regulated IL-6 and IL-8 secretion, and KIRA6 blunted these responses in a dose-dependent manner. Moreover, a triple combination of CFTR modulators currently used in the clinic had no effect on SMM-increased XBP-1s levels coupled with increased cytokine production in presence or absence of KIRA6. These findings indicate that IRE1α mediates cytokine production in CF airways. Small molecule IRE1α kinase inhibitors that allosterically reduce RNase-dependent XBP-1s may represent a new therapeutic strategy for CF airway inflammation.


Assuntos
Fibrose Cística/tratamento farmacológico , Fibrose Cística/patologia , Endorribonucleases/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão/patologia , Terapia de Alvo Molecular , Proteínas Serina-Treonina Quinases/metabolismo , Células Cultivadas , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Citocinas/biossíntese , Endorribonucleases/genética , Epitélio/efeitos dos fármacos , Epitélio/patologia , Humanos , Imidazóis/química , Imidazóis/farmacologia , Inflamação/genética , Modelos Biológicos , Naftalenos/química , Naftalenos/farmacologia , Proteínas Serina-Treonina Quinases/genética , Pirazinas/química , Pirazinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Proteína 1 de Ligação a X-Box/metabolismo
3.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806206

RESUMO

In this study, we evaluated the improved memristive switching characteristics of hydrogen silsesquioxane (HSQ) nanocomposites embedded with a single-walled carbon nanotube (SWCNT) random network. A low-temperature solution process was implemented using a flexible memristor device on a polyethylene naphthalate (PEN) substrate. The difference in the resistive switching (RS) behavior due to the presence of the SWCNT random network was analyzed by the current transport mechanism. Such a random network not only improves the RS operation but also facilitates a stable multilevel RS performance. The multiple-resistance states exhibited highly reliable nonvolatile retention properties over 104 s at room temperature (25 °C) and at a high temperature (85 °C), showing the possibility of an analog synaptic weight modulation. Consequently, the gradual weight potentiation/depression was realized through 3 × 102 synaptic stimulation pulses. These findings suggest that the embedded SWCNT random network can improve the synaptic weight modulation characteristics with high stability for an artificial synapse and hence can be used in future neuromorphic circuits.


Assuntos
Hidrogênio/química , Nanotubos de Carbono/química , Compostos de Organossilício/química , Simulação por Computador , Condutividade Elétrica , Desenho de Equipamento , Teste de Materiais , Nanocompostos/química , Naftalenos/química , Redes Neurais de Computação , Polietilenos/química , Temperatura
4.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669147

RESUMO

An aniline-functionalized naphthalene dialdehyde Schiff base fluorescent probe L with aggregation-induced enhanced emission (AIEE) characteristics was synthesized via a simple one-step condensation reaction and exhibited excellent sensitivity and selectivity towards copper(II) ions in aqueous media with a fluorescence " turn-off " phenomenon. The detection limit of the probe is 1.64 × 10-8 mol·L-1. Furthermore, according to the results of the UV-vis/fluorescence titrations, Job's plot method and 1H-NMR titrations, a 1:2 stoichiometry was identified. The binding constant between L and Cu2+ was calculated to be Ka = 1.222 × 103. In addition, the AIEE fluorescent probe L could be applied to detection in real water samples with satisfactory recoveries in the range 99.10-102.90% in lake water and 98.49-102.37% in tap water.


Assuntos
Cobre/análise , Corantes Fluorescentes/química , Naftalenos/química , Poluentes Químicos da Água/análise , Cristalografia por Raios X , Corantes Fluorescentes/síntese química , Íons/análise , Modelos Moleculares , Estrutura Molecular , Naftalenos/síntese química , Bases de Schiff/síntese química , Bases de Schiff/química
5.
Molecules ; 26(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671758

RESUMO

As a candidate for bifunctional asymmetric catalysts containing a half-sandwich C-N chelating Ir(III) framework (azairidacycle), a dinuclear Ir complex with an axially chiral linkage is newly designed. An expedient synthesis of chiral 2,2'-bis(aminomethyl)-1,1'-binaphthyl (1) from 1,1-bi-2-naphthol (BINOL) was accomplished by a three-step process involving nickel-catalyzed cyanation and subsequent reduction with Raney-Ni and KBH4. The reaction of (S)-1 with an equimolar amount of [IrCl2Cp*]2 (Cp* = η5-C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 °C gave a diastereomeric mixture of new dinuclear dichloridodiiridium complexes (5) through the double C-H bond cleavage, as confirmed by 1H NMR spectroscopy. A loss of the central chirality on the Ir centers of 5 was demonstrated by treatment with KOC(CH3)3 to generate the corresponding 16e amidoiridium complex 6. The following hydrogen transfer from 2-propanol to 6 provided diastereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%.


Assuntos
Compostos Aza/química , Complexos de Coordenação/química , Irídio/química , Naftalenos/química , Complexos de Coordenação/síntese química , Conformação Molecular
6.
Int J Biol Macromol ; 176: 520-529, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607140

RESUMO

Naftopidil (NAF), an α1-adrenoceptor antagonist, is administered as a treatment for benign prostatic hyperplasia; however, according to the Biopharmaceutical Classification System (BCS IV), it is a poorly-soluble drug that exhibits poor permeability. We aimed to increase the dissolution (%) of NAF by adding chitosan to a polymer-free formulation. Compared to the formulation prepared using Flivas®, at 60 min, the solid dispersion (SD) formulation containing NAF, fumaric acid, chitosan, and US2® in a 1:1:2:1 weight ratio improved the dissolution (%) of NAF in distilled water, pH 1.2 media, pH 4.0 and pH 6.8 buffers by 27.2-, 1.2-, 1.1- and 6.5-fold, respectively. The physicochemical properties of the SD1 formulation were also found to be altered, including its thermal properties, crystal intensity, and chemical interaction. As a result, the hydrogen bonding that occurs between NAF and fumaric acid was identified as a major factor in the increase in NAF dissolution (%). Further, chitosan was observed to contribute to the stability of NAF and SD1, which was assessed over a 3-month period. To our knowledge, this is the first study to employ a polymer-free system to improve the solubilization of NAF.


Assuntos
Quitosana/química , Fumaratos/química , Naftalenos/química , Piperazinas/química , Solubilidade
7.
Molecules ; 26(4)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33557184

RESUMO

Stereoselective reactions of singlet oxygen are of current interest. Since enantioselective photooxygenations have not been realized efficiently, auxiliary control is an attractive alternative. However, the obtained peroxides are often too labile for isolation or further transformations into enantiomerically pure products. Herein, we describe the oxidation of naphthalenes by singlet oxygen, where the face selectivity is controlled by carbohydrates for the first time. The synthesis of the precursors is easily achieved starting from naphthoquinone and a protected glucose derivative in only two steps. Photooxygenations proceed smoothly at low temperature, and we detected the corresponding endoperoxides as sole products by NMR. They are labile and can thermally react back to the parent naphthalenes and singlet oxygen. However, we could isolate and characterize two enantiomerically pure peroxides, which are sufficiently stable at room temperature. An interesting influence of substituents on the stereoselectivities of the photooxygenations has been found, ranging from 51:49 to up to 91:9 dr (diastereomeric ratio). We explain this by a hindered rotation of the carbohydrate substituents, substantiated by a combination of NOESY measurements and theoretical calculations. Finally, we could transfer the chiral information from a pure endoperoxide to an epoxide, which was isolated after cleavage of the sugar chiral auxiliary in enantiomerically pure form.


Assuntos
Carboidratos/química , Naftalenos/química , Oxigênio Singlete/química , Reação de Cicloadição , Modelos Moleculares , Conformação Molecular , Estereoisomerismo
8.
Food Chem ; 349: 128982, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561797

RESUMO

This paper reports a selective, sensitive, and miniaturized analytical method based on a molecularly imprinted graphene oxide (MIP-GO) composite as adsorbent for miniaturized tip solid-phase extraction (MTSPE) to determine naphthalene-derived plant growth regulators (PGRs) in apples. The proposed method combines the advantages of MIP-GOs (high selectivity), MTSPE (low consumption), and high-performance liquid chromatography-fluorescence detection (high sensitivity). Under optimized conditions, the method exhibited appreciable linearity (2.00-200 ng/g), low detection limits (0.21-0.53 ng/g), high accuracy (absolute recoveries: 87.6-99.5%), and high precision (relative standard deviations ≤ 3.0%), along with low consumption (0.5 mL sample solution and 2.0 mg adsorbent). In addition, the adsorption performance of the MIP-GO adsorbent did not decrease over ten months, highlighting the long storage and operational lifetime of the adsorbent. The proposed method was employed for the analysis of naphthalene-derived PGR residues in apples and exhibited promising potential for application in food safety analysis.


Assuntos
Análise de Alimentos/métodos , Grafite/química , Malus/química , Impressão Molecular , Naftalenos/química , Reguladores de Crescimento de Plantas/análise , Reguladores de Crescimento de Plantas/química , Adsorção , Cromatografia Líquida de Alta Pressão , Limite de Detecção , Extração em Fase Sólida/métodos , Fatores de Tempo
9.
Anal Chem ; 93(4): 2578-2588, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33432809

RESUMO

Surface-enhanced Raman scattering (SERS) is an ultrasensitive analytical technique, which is capable of providing high specificity; thus, it can be used for toxicological drug assay (detection and quantification). However, SERS-based drug analysis directly in human biofluids requires mitigation of fouling and nonspecificity effects that commonly appeared from unwanted adsorption of endogenous biomolecules present in biofluids (e.g., blood plasma and serum) onto the SERS substrate. Here, we report a bottom-up fabrication strategy to prepare ultrasensitive SERS substrates, first, by functionalizing chemically synthesized gold triangular nanoprisms (Au TNPs) with poly(ethylene glycol)-thiolate in the solid state to avoid protein fouling and second, by generating flexible plasmonic patches to enhance SERS sensitivity via the formation of high-intensity electromagnetic hot spots. Poly(ethylene glycol)-thiolate-functionalized Au TNPs in the form of flexible plasmonic patches show a twofold-improved signal-to-noise ratio in comparison to triethylamine (TEA)-passivated Au TNPs. Furthermore, the plasmonic patch displays a SERS enhancement factor of 4.5 ×107. Utilizing the Langmuir adsorption model, we determine the adsorption constant of drugs for two different surface ligands and observe that the drug molecules display stronger affinity for poly(ethylene glycol) ligands than TEA. Our density functional theory calculations unequivocally support the interaction between drug molecules and poly(ethylene glycol) moieties. Furthermore, the universality of the plasmonic patch for SERS-based drug detection is demonstrated for cocaine, JWH-018, and opioids (fentanyl, despropionyl fentanyl, and heroin) and binary mixture (trace amount of fentanyl in heroin) analyses. We demonstrate the applicability of flexible plasmonic patches for the selective assay of fentanyl at picogram/milliliter concentration levels from drug-of-abuse patients' blood plasma. The fentanyl concentration calculated in the patients' blood plasma from SERS analysis is in excellent agreement with the values determined using the paper spray ionization mass spectrometry technique. We believe that the flexible plasmonic patch fabrication strategy would be widely applicable to any plasmonic nanostructure for SERS-based chemical sensing for clinical toxicology and therapeutic drug monitoring.


Assuntos
Análise Espectral Raman/métodos , Cocaína/química , Fentanila/química , Toxicologia Forense/métodos , Ouro/química , Heroína/química , Humanos , Indóis/química , Limite de Detecção , Espectrometria de Massas , Nanopartículas Metálicas/química , Naftalenos/química , Preparações Farmacêuticas , Plasma
10.
Anal Chem ; 93(4): 2152-2159, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33406831

RESUMO

The macrophage migration inhibitory factor (MIF), a vital cytokine and biomarker, has been suggested to closely associate with the pathogenesis of liver cancer. However, a simple and effective approach for monitoring the change and distribution of cellular MIF is currently lacking and urgently needed, which could be helpful for a better understanding of its role in the progression of cancer. Herein, we report a novel activity-based probe, TPP2, which allows for direct labeling and imaging of endogenous MIF activity within live cells, clinical tissues, and in vivo in a mouse model of liver cancer. With this probe, we have intuitively observed the dynamic change of intracellular MIF activity by both flow cytometry and confocal imaging. We further found that TPP2 permits the identification and distinguishing of liver cancer in vitro and in vivo with high sensitivity and selectivity toward MIF. Our observations indicate that TPP2 could provide a promising new imaging approach for elucidating the MIF-related biological functions in liver cancer.


Assuntos
Fatores Inibidores da Migração de Macrófagos/metabolismo , Naftalenos/farmacologia , Animais , Linhagem Celular Tumoral , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Naftalenos/química , Neoplasias Experimentais , Ligação Proteica , Conformação Proteica , Proteoma , Análise de Célula Única
11.
AAPS PharmSciTech ; 22(1): 33, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404930

RESUMO

Onychomycosis is considered a stubborn nail fungal infection that does not respond to conventional topical antifungal treatments. This study aimed to develop and characterize novel solid lipid nanoparticles (SLNs) formulae containing terbinafine HCl (TFH) and loaded with different nail penetration enhancers (nPEs). Three (nPEs) N-acetyl-L-cysteine, thioglycolic acid, and thiourea were used. Characterization of the prepared formulae was done regarding particle size, zeta potential, polydispersity index (PDI), entrapment efficiency (EE%), physical stability, in vitro release study, infrared (FT-IR), and their morphological structures. The selected formulae and the marketed cream Lamifen® were compared in terms of their antifungal activity against Trichophyton rubrum as well as their nail hydration and their drug uptake by the nail clippers. Thiourea was the nPE of choice; formulae (N2 and N8), with thiourea, were considered the optimum TFH SLNs containing nPEs. They were selected for their optimum particle size of 426.3 ± 10.18 and 450.8 ± 11.45 nm as well as their highest EE% of 89.76 ± 1.25 and 90.35 ± 1.33, respectively. The in vitro microbiological screening of the antifungal activity of these two formulae showed significantly larger zones of inhibition in comparison with the marketed product. The ex vivo screening of the drug uptake of the two selected formulae was significantly higher than that of the marketed product. The nPE formulae present a very promising option as they showed optimum physicochemical characterization with high antifungal activity and high drug uptake as well as good nail hydration effect.


Assuntos
Antifúngicos/uso terapêutico , Lipídeos/química , Unhas/metabolismo , Nanopartículas/química , Onicomicose/tratamento farmacológico , Terbinafina/uso terapêutico , Administração Tópica , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Arthrodermataceae , Humanos , Naftalenos/química , Onicomicose/microbiologia , Preparações Farmacêuticas , Espectroscopia de Infravermelho com Transformada de Fourier , Terbinafina/administração & dosagem , Terbinafina/farmacocinética
12.
Chem Commun (Camb) ; 57(13): 1603-1606, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33463645

RESUMO

Herein, we have unravelled the key influence of aromatic interactions on the mechanistic pathways of peptide self-assembly by introducing suitable chromophores (pyrene vs. naphthalene). Although both self-assembled peptides are indistinguishable in their morphologies, this minor structural difference strongly affects the packing modes (parallel vs. antiparallel) and the corresponding self-assembly mechanism (cooperative vs. isodemsic).


Assuntos
Naftalenos/química , Peptídeos/química , Pirenos/química , Interações Hidrofóbicas e Hidrofílicas , Conformação Proteica
13.
Eur J Med Chem ; 213: 113039, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33261898

RESUMO

Building on our previous work that discovered 1,2,4-triazole-spirodienone as a promising pharmacophore for anticancer activity, we have further diversified 1,2,4-triazole- spirodienone derivatives and synthesized a series of novel naphthalene-substituted triazole spirodienones to explore their antineoplastic activity. Of these, compound 6a possesses remarkable in vitro cytotoxic activity by arresting cell cycle and inducing apoptosis in MDA-MB-231 cells. Subsequently, acute toxicity assay showed that 6a at 20 mg/kg has no apparent toxicity to the major organ in mice. In addition, compound 6ain vivo suppressed breast cancer 4T1 tumor growth. Taken together, these results indicate that compound 6a may be a potential anticancer agent for further development.


Assuntos
Antineoplásicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Naftalenos/química , Triazóis/síntese química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Camundongos , Relação Estrutura-Atividade , Triazóis/farmacologia
14.
Int J Biol Macromol ; 166: 1320-1334, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33166559

RESUMO

To selectively target telomeric G-quadruplex (G4) DNA, monomeric and dimeric naphthalene diimides (NDIs) were investigated as binders of multimeric G4 structures able to discriminate duplex DNA. These NDIs were analysed by the affinity chromatography-based screening G4-CPG (G-quadruplex on Controlled Pore Glass), using the sequence d[AGGG(TTAGGG)7] (tel46), folding into two consecutive G4s, as model of the human telomeric G4 multimer. In parallel, a telomeric G4 monomer (tel26) and a duplex structure (ds27) were used as controls. According to G4-CPG screening, NDI-5 proved to be the best ligand in terms of dimeric G4 vs. duplex DNA selectivity and was analysed by circular dichroism (CD), gel electrophoresis, isothermal titration calorimetry (ITC) and fluorescence spectroscopy in its interactions with tel46. NDI-5 strongly binds and stabilizes tel46 G4, favouring a hybrid folding in K+-containing buffer. Under these conditions, the binding process comprises a first event involving three molecules of NDI-5 and a second one in which other six molecules bind to the DNA. In a metal cation-free system, NDI-5 induces tel46 G4 folding, as indicated by CD and PAGE, favouring an antiparallel structuring. Docking simulations showed that NDI-5 can effectively bind to the pocket between two G4 units, representing a promising ligand for multimeric G4s.


Assuntos
Quadruplex G , Imidas/química , Substâncias Intercalantes/química , Naftalenos/química , Humanos , Simulação de Acoplamento Molecular , Telômero/química
15.
Insect Sci ; 28(2): 392-402, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32394613

RESUMO

Owing to their potential applications, as well as their structural diversity, the discovery of novel secondary metabolites from insect-associated fungi has been of interest to researchers in recent years. The aim of this study was therefore to estimate the diversity of fungi associated with fungus-growing termites and bioprospecting these for potential secondary metabolites. In total, 18 fungal species were isolated and described from the gut and comb of Macrotermes barneyi based on 18S ribosomal DNA gene sequence analysis. Antimicrobial activity assays were carried out on all the known fungi, and nine isolates were recorded as active against pathogenic fungi. Xylaria escharoidea, the best performing isolate, was grown at laboratory scale and 4,8-dihydroxy-3,4-dihydronaphthalen-1(2H) was isolated and characterized. The minimum inhibitory concentration of this isolated compound against tested pathogenic organisms was found to be 6.25 µg. In addition, molecular docking studies have revealed that 4,8-dihydroxy-3,4-dihydronaphthalen-1(2H) is a prominent antibacterial agent with a marked interaction with key residues on protein A (agrAC ) that regulates the accessory gene. The findings of this study support the drug discovery of antimicrobial properties in insect-associated fungi, which may lead to novel secondary metabolites.


Assuntos
Anti-Infecciosos/isolamento & purificação , Ascomicetos/química , Fungos/isolamento & purificação , Isópteros/microbiologia , Naftalenos/isolamento & purificação , RNA Ribossômico 18S/análise , Animais , Anti-Infecciosos/química , Fungos/classificação , Fungos/fisiologia , Naftalenos/química , RNA Fúngico/análise , Análise de Sequência de DNA , Simbiose
16.
Int J Biol Macromol ; 167: 1048-1058, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33188810

RESUMO

G-quadruplexes (GQs) have become promising anti-cancer therapeutic targets, which are formed by the folding of a guanine-rich repeat DNA/RNA sequence at human telomeres or oncogene promoters. Polymorphism has been observed for the folding topologies of intramolecular GQs. Here we report the topological conversion of human telomeric GQ induced by naphthalene diimide (NDI) ligands in K+ solution. The ligands selectively induce metastable hybrid-type GQs to highly stable parallel-type GQ at physiological temperature (37 °C) in dilute aqueous solutions and under crowding conditions that mimic cellular bioenvironment. According to spectroscopic analyses, the topological conversion is speculated to undergo stepwise unfolding of hybrid-type GQ through intermediate states to parallel-type GQ. The results will prompt further studies on the designs of ligands with GQ conformation regulation functions and nanotechnological systems based on nucleic acids with dynamic regulation of GQ conformation.


Assuntos
DNA/química , Quadruplex G , Imidas/química , Naftalenos/química , Telômero/química , Humanos , Ligantes , Fenômenos Mecânicos , Modelos Moleculares , Estrutura Molecular , Conformação de Ácido Nucleico , Análise Espectral , Relação Estrutura-Atividade , Telômero/genética
17.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375008

RESUMO

Supramolecular aggregates formed between polycyclic aromatic hydrocarbons and either naphthalene or perylene-derived diimides have been anchored in magnetite magnetic nanoparticles. The high affinity and stability of these aggregates allow them to capture and confine these extremely carcinogenic contaminants in a reduced space. In some cases, the high cohesion of these aggregates leads to the formation of magnetic microfibres of several microns in length, which can be isolated from the solution by the direct action of a magnet. Here we show a practical application of bioremediation aimed at the environmental decontamination of naphthalene, a very profuse contaminant, based on the uptake, sequestration, and acceleration of the biodegradation of the formed supramolecular aggregate, by the direct action of a bacterium of the lineage Roseobacter (biocompatible with nanostructured receptors and very widespread in marine environments) without providing more toxicity to the environment.


Assuntos
Microfibrilas/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Roseobacter/metabolismo , Água do Mar/microbiologia , Biodegradação Ambiental , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/microbiologia , Nanopartículas de Magnetita/ultraestrutura , Microfibrilas/microbiologia , Microfibrilas/ultraestrutura , Microscopia Eletrônica de Varredura , Estrutura Molecular , Naftalenos/química , Naftalenos/metabolismo , Tamanho da Partícula , Hidrocarbonetos Policíclicos Aromáticos/química
18.
World J Microbiol Biotechnol ; 36(12): 181, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164140

RESUMO

Although the use of degrading-bacteria is one of the most efficient methods for the bioremediation of polluted sites, detection, selection and proliferation of the most efficient and competing bacteria is still a challenge. The objective of this multi-stage research was to investigate the effects of the selected bacterial strains on the degradation of anthracene, florentine, naphthalene, and oil, determined by biochemical tests. In the first stage, using the following tests: (a) biosurfactant production (emulsification, oil spreading, number of drops, drop collapse, and surface tension), (b) biofilm production, (c) activity of laccase enzyme, and (d) exopolysaccaride production, the three bacterial strains with the highest degrading potential including Bacillus pumilus, B. aerophilus, and Marinobacter hydrocarbonoclasticus were chosen. In the second stage using the following tests: (a) bacterial growth, (b) laccase enzyme activity, and (c) biosurfactant production (emulsification, oil spreading, and collapse of droplet) the degrading ability of the three selected bacterial strains plus Escherichia coli were compared. Different bacterial strains were able to degrade anthracene, florentine, naphthalene, and oil by the highest rate, three days after inoculation (DAI). However, M. hydrocarbonoclasticus showed the highest rate of florentine degradation. Although with increasing pollutant concentration the degrading potential of the bacterial strains significantly decreased, M. hydrocarbonoclasticus was determined as the most efficient bacterial strain.


Assuntos
Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Poluentes Ambientais/química , Hidrocarbonetos Policíclicos Aromáticos/química , Antracenos/química , Bacillus/crescimento & desenvolvimento , Bacillus/metabolismo , Bacillus pumilus/crescimento & desenvolvimento , Bacillus pumilus/metabolismo , Bactérias/isolamento & purificação , Biodegradação Ambiental , Biofilmes , Biocombustíveis/análise , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Lacase/metabolismo , Marinobacter/crescimento & desenvolvimento , Marinobacter/metabolismo , Naftalenos/química , Polissacarídeos Bacterianos/metabolismo , Tensoativos/metabolismo
19.
Molecules ; 25(21)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33142979

RESUMO

A novel family of water-soluble π-conjugated hexaazatrinaphthylenes-based dendritic architectures constructed by hexaketocyclohexane and 1,2,4,5-benzenetetramine units is developed in a microwave-assisted organic synthesis (MAOS) approach. The structures and purity of these compounds are verified by 1H and 13C-NMR, MALDI-TOF MS, UV-vis, elemental analysis, DSC, AFM, STM and cyclic voltammetry.


Assuntos
Dendrímeros/química , Dendrímeros/síntese química , Micro-Ondas , Naftalenos/química , Naftalenos/síntese química
20.
Molecules ; 25(21)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172000

RESUMO

An efficient synthetic route to highly functionalized naphthalenes and quinolines has been developed using domino reactions between Morita-Baylis-Hillman (MBH) acetates and active methylene compounds (AMCs) promoted by anhydrous K2CO3 in dry N,N-dimethylformamide (DMF) at 23 °C. The substrates incorporate allylic acetates positioned adjacent to a Michael acceptor as well as an aromatic ring activated toward a SNAr ring closure. A control experiment indicated that the initial reaction was an SN2'-type displacement of a side chain acetoxy by the AMC anion to afford the alkene product bearing the added nucleophile trans to the SNAr aromatic ring acceptor. Thus, equilibration of the alkene geometry of the initial product was required prior to cyclization. Products were isolated in good to excellent yields. Numerous cases (24) are reported, and several mechanistic possibilities are discussed.


Assuntos
Naftalenos/química , Quinolinas/química , Acetatos/química , Compostos Alílicos/química , Estrutura Molecular , Naftalenos/síntese química , Quinolinas/síntese química
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