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1.
Life Sci ; 269: 119066, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460663

RESUMO

AIMS: This study aimed to investigate the effect of previously synthesized 4,5-diazafluorene derivative (14c) on γδ T cell-mediated cytotoxicity against renal cell carcinoma (RCC). MATERIALS AND METHODS: A real-time cell analyzer monitored cell proliferation, and Cell Counting Kit-8 determined cell viability. A reverse transcription-polymerase chain reaction analyzed gene expression, and protein expression was determined by cellular immunofluorescence analysis and Western blot. KEY FINDINGS: The compound 14c induced the expression of immunomodulatory molecules, such as natural killer group 2, member D ligands (NKG2DLs), fibroblast-associated (Fas) death receptor, and tumor necrosis factor-related apoptosis-inducing ligand receptors (TRAILRs) in RCC. In addition, 14c induced DNA damage responses in RCC. Blocking DNA damage by KU-55933 reduced the effect of γδ T cells on 14c-treated RCC, suggesting that DNA damage responses were involved in the augmentation of γδ T cell-mediated cytotoxicity. Treating 786-O cells with a nitrogen-containing bisphosphonate prodrug further enhanced the anti-tumor effect of γδ T cell plus 14c combination treatment. SIGNIFICANCE: The present evidence indicates that 14c induced DNA damage responses in RCC and augmented γδ T cell-mediated cytotoxicity primarily through NKG2D/NKG2DLs pathways, suggesting potential cancer immunotherapy for harnessing γδ T cells and small compounds that induce DNA damage responses.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Renais/patologia , Citotoxicidade Imunológica/imunologia , Imunidade Celular/imunologia , Compostos Organometálicos/farmacologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Antineoplásicos/química , Compostos Aza/química , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Proliferação de Células , Dano ao DNA , Fluorenos/química , Humanos , Imunidade Celular/efeitos dos fármacos , Imunomodulação , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Compostos Organometálicos/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Células Tumorais Cultivadas
2.
Ecotoxicol Environ Saf ; 208: 111621, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396141

RESUMO

The study explored the polycyclic aromatic hydrocarbon tolerance of indigenous biosurfactant producing microorganisms. Three bacterial species were isolated from crude oil contaminated sites of Haldia, West Bengal. The three species were screened for biosurfactant production and identified by 16S rRNA sequencing as Brevundimonas sp. IITISM 11, Pseudomonas sp. IITISM 19 and Pseudomonas sp. IITISM 24. The strains showed emulsification activities of 51%, 57% and 63%, respectively. The purified biosurfactants were characterised using FT-IR, GC-MS and NMR spectroscopy and found to have structural similarities to glycolipopeptides, cyclic lipopeptides and glycolipids. The biosurfactants produced were found to be stable under a wide range of temperature (0-100 °C), pH (4-12) and salinity (up to 20% NaCl). Moreover, the strains displayed tolerance to high concentrations (275 mg/L) of anthracene and fluorene and showed a good amount of cell surface hydrophobicity with different hydrocarbons. The study reports the production and characterisation of biosurfactant by Brevundimonas sp. for the first time. Additionally, the kinetic parameters of the bacterial strains grown on up to 300 mg/L concentration of anthracene and fluorene, ranged between 0.0131 and 0.0156 µmax (h-1), while the Ks(mg/L) ranged between 59.28 and 102.66 for Monod's Model. For Haldane-Andrew's model, µmax (h-1) varied between 0.0168 and 0.0198. The inhibition constant was highest for Pseudomonas sp. IITISM 19 on anthracene and Brevundimonas sp. IITISM 11 on fluorene. The findings of the study suggest that indigenous biosurfactant producing strains have tolerance to high PAH concentrations and can be exploited for bioremediation purposes.


Assuntos
Antracenos/metabolismo , Biodegradação Ambiental , Fluorenos/metabolismo , Tensoativos/metabolismo , Antracenos/química , Bactérias/metabolismo , Fluorenos/química , Glicolipídeos , Hidrocarbonetos/metabolismo , Cinética , Petróleo/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pseudomonas/metabolismo , RNA Ribossômico 16S/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química
3.
Macromol Rapid Commun ; 41(15): e2000249, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32608545

RESUMO

A thermo-responsive conjugated polymer, PFBT-gPA is synthesized by grafting the poly(N-isopropylacrylamide) (PNIPAAm) to the side chains of a conjugated polyfluorene derivative through atom transfer radical polymerization (ATRP). PFBT-gPA undergoes a reversible phase transition in water below and above the lower critical solution temperature (LCST) and the process is studied by differential scanning calorimetry (DSC) analysis and UV/vis absorption spectra. PFBT-gPA shows a good photostability under UV light irradiation especially above the LCST. Moreover, the photosensitizing performance of PFBT-gPA could be tuned simply by changing temperature. The unique properties of PFBT-gPA promise its potential applications in sensing and photodynamic therapy.


Assuntos
Resinas Acrílicas/química , Fluorenos/química , Polímeros/química , Varredura Diferencial de Calorimetria , Espectroscopia de Ressonância Magnética , Transição de Fase , Fotodegradação , Fármacos Fotossensibilizantes/química , Polimerização , Polímeros/síntese química , Polímeros/efeitos da radiação , Espectrometria de Fluorescência , Temperatura , Água/química
4.
J Chromatogr A ; 1621: 461078, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32312546

RESUMO

A new derivatization reagent, N-(naphthalen-1-yl)-2-oxopropanehydrazonoyl chloride (UOSA54), was prepared and coupled with four drugs, bearing primary amino, secondary amino or mercapto functional groups. Glucosamine sulfate (GLU), cysteine (CYS), captopril (CAP), and vildagliptin (VIL), were used as representative reactive analytes. The prepared reagent was successfully coupled with the targeted analytes in the presence of triethylamine (TEA) as hydrochloride acceptor and acetonitrile as solvent. The resulting reaction products were separated by high-performance liquid chromatography and monitored simultaneously by diode array and triple quad mass spectrometry detectors. Enhanced DAD and electrospray ionization-MS (ESI-MS) responses were observed for the derivatized products. Complete derivatization of VIL was achieved after heating at 65 ± 3 °C for 4 min, while other analytes were derivatized instantaneously at room temperature. Both, the ESI-ionization suppression, due to the excess reagent, and matrix effect, due to co-eluted biogenic plasma constituents, were negligible. The derivatized GLU, CYS, CAP, and VIL showed a maximum absorption wavelength at 376, 417, 340, and 376 nm, with MS-limit of quantification value of 250.0, 2.0, 2.5, and 3.0 pg/µL, respectively. The relative ESI-MS response of UOSA54 derivatization products was within the range of 0.6-4.1 compared with dansylated products. The method was optimized and validated for optimal reaction product stability, sensitivity, linearity, range, precision, and accuracy. The percentage recovery was exceeding 97.2%, with an RSD value of less than 4.0%. The limit of quantification of targeted analytes was ranged from 80.0 to 0.7 pg/µL.


Assuntos
Aminas/análise , Cromatografia Líquida/métodos , Iminas/análise , Espectrometria de Massas/métodos , Compostos de Sulfidrila/análise , Cromatografia Líquida de Alta Pressão , Compostos de Dansil/química , Fluorenos/síntese química , Fluorenos/química , Reprodutibilidade dos Testes , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química
5.
Acta Crystallogr C Struct Chem ; 76(Pt 4): 328-345, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32229714

RESUMO

Recently, fluorenylmethoxycarbonyl (Fmoc) amino acids (e.g. Fmoc-tyrosine or Fmoc-phenylalanine) have attracted growing interest in biomedical research and industry, with special emphasis directed towards the design and development of novel effective hydrogelators, biomaterials or therapeutics. With this in mind, a systematic knowledge of the structural and supramolecular features in recognition of those properties is essential. This work is the first comprehensive summary of noncovalent interactions combined with a library of supramolecular synthon patterns in all crystal structures of amino acids with the Fmoc moiety reported so far. Moreover, a new Fmoc-protected amino acid, namely, 2-{[(9H-fluoren-9-ylmethoxy)carbonyl](methyl)amino}-3-{4-[(2-hydroxypropan-2-yl)oxy]phenyl}propanoic acid or N-fluorenylmethoxycarbonyl-O-tert-butyl-N-methyltyrosine, Fmoc-N-Me-Tyr(t-Bu)-OH, C29H31NO5, was successfully synthesized and the structure of its unsolvated form was determined by single-crystal X-ray diffraction. The structural, conformational and energy landscape was investigated in detail by combined experimental and in silico approaches, and further compared to N-Fmoc-phenylalanine [Draper et al. (2015). CrystEngComm, 42, 8047-8057]. Geometries were optimized by the density functional theory (DFT) method either in vacuo or in solutio. The polarizable conductor calculation model was exploited for the evaluation of the hydration effect. Hirshfeld surface analysis revealed that H...H, C...H/H...C and O...H/H...O interactions constitute the major contributions to the total Hirshfeld surface area in all the investigated systems. The molecular electrostatic potentials mapped over the surfaces identified the electrostatic complementarities in the crystal packing. The prediction of weak hydrogen-bonded patterns via Full Interaction Maps was computed. Supramolecular motifs formed via C-H...O, C-H...π, (fluorenyl)C-H...Cl(I), C-Br...π(fluorenyl) and C-I...π(fluorenyl) interactions are observed. Basic synthons, in combination with the Long-Range Synthon Aufbau Modules, further supported by energy-framework calculations, are discussed. Furthermore, the relevance of Fmoc-based supramolecular hydrogen-bonding patterns in biocomplexes are emphasized, for the first time.


Assuntos
Aminoácidos/química , Fluorenos/síntese química , Metiltirosinas/química , Fenilalanina/química , Aminoácidos/síntese química , Simulação por Computador , Cristalografia por Raios X , Fluorenos/química , Ligação de Hidrogênio , Conformação Molecular , Inquéritos e Questionários
6.
Biomater Sci ; 8(7): 1996-2006, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32073033

RESUMO

Recently, fluorenylmethyloxycarbonyl (Fmoc) conjugated amino acids (Fmoc-AA), especially Fmoc-phenylalanine (Fmoc-F), have been discovered to have antimicrobial properties specific to Gram-positive bacteria including MRSA. Their weak antibacterial activity against Gram-negative bacteria is due to their inability to cross the bacterial membrane. Here in order to increase the antibacterial spectrum of Fmoc-F, we prepared a formulation of Fmoc-F with the Gram-negative specific antibiotic aztreonam (AZT). This formulation displayed antibacterial activity against both Gram-positive and Gram-negative bacteria and significantly reduced the bacterial load in a mouse wound infection model. The combination produced a synergistic effect and higher efficacy against P. aeruginosa due to the increased Fmoc-F permeability by AZT through the bacterial membrane. This combinatorial approach could be an effective strategy for other Fmoc-AA having a Gram-positive specific antibacterial effect for the better management of bacterial wound infections.


Assuntos
Antibacterianos/administração & dosagem , Aztreonam/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Dipeptídeos/química , Fluorenos/química , Infecção dos Ferimentos/microbiologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Aztreonam/química , Aztreonam/farmacologia , Carga Bacteriana/efeitos dos fármacos , Modelos Animais de Doenças , Sinergismo Farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hidrogéis , Camundongos , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos/tratamento farmacológico
7.
J Chromatogr A ; 1619: 460939, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32085912

RESUMO

Glyphosate (Glyp) and glufosinate (Gluf) are widely used herbicides around the world, and their effects on human health and detection of levels have drawn increasing attention. The present study was to establish a method to determine the contents of Glyp and Gluf from corn using multi-walled carbon nanotubes (MWCNTs) followed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The corn samples were purified by MWCNTs, then the analytes reacted with 9-fluorenylmethylchloroformate (FMOCCl) of acetonitrile solution (20.0 g/L) at 50 °C water bath in a borate buffer solution (50.0 g/L, pH=9) to generate FMOC derivative products. After the derivatization, HSS T3 was used as the separation column, with acetonitrile and 0.05% ammonia as the mobile phase, and multiple reaction monitoring (MRM) mode with negative electrospray ionization (ESI-) was adopted. The validation parameters showed good verification results, with both of their quantitative limits (LOQ) as 0.005 mg/kg, recoveries between 90.3% and 95.4%, intra-day relative standard deviations (RSDs) in the ranges of 1.24% and 3.35%, and inter-day RSDs between 3.56% and 6.06%. The analytical method, developed in this study, has high accuracy and sensitivity, and is suitable for the simultaneous detection of Glyp and Gluf in corn.


Assuntos
Aminobutiratos/análise , Cromatografia Líquida de Alta Pressão , Análise de Alimentos/métodos , Glicina/análogos & derivados , Espectrometria de Massas em Tandem , Zea mays/química , Acetonitrilos/química , Fluorenos/química , Glicina/análise , Herbicidas/análise , Nanotubos de Carbono/química , Reprodutibilidade dos Testes
8.
Org Lett ; 22(4): 1563-1568, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32043885

RESUMO

The first example of metal-free cyanomethylenation from alkyl nitriles of sp3 C-H bonds to afford quaternary carbon centers is described. This oxidative protocol is operationally simple and features good functional group compatibility. This method provides a novel approach to highly functionalized fluorene and oxindole derivatives, which are commonly used in material and pharmaceutical areas. Control experiments provide evidence of a radical reaction process.


Assuntos
Cianetos/síntese química , Fluorenos/química , Nitrilos/química , Oxindois/química , Cianetos/química , Metilação , Estrutura Molecular , Oxirredução , Estereoisomerismo
9.
Chem Commun (Camb) ; 56(25): 3657-3660, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32108200

RESUMO

We report blue- and green-emitting two-photon probes derived from naphthalene and fluorene derivatives (as fluorophores) and an endoplasmic reticulum (ER) retrieval peptide (KDEL; as an ER-targeting moiety) that can detect the ER in a live cell by both one-photon and two-photon microscopy (TPM) and in a live tissue by TPM.


Assuntos
Retículo Endoplasmático/química , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica , Fótons , Fluorenos/química , Células HeLa , Humanos , Estrutura Molecular , Naftalenos/química , Imagem Óptica , Peptídeos/química
10.
Molecules ; 25(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979298

RESUMO

Design of elaborated nanomaterials to improve the therapeutic efficacy and mitigate the side effects of chemotherapeutic anticancer drugs, such as Doxorubicin (Dox), is significant for cancer treatment. Here, we describe a co-assembled strategy, where amphiphile short peptides are co-assembled with Doxorubicin to form nanoscale particles for enhanced delivery of Dox. Two kinds of short peptides, Fmoc-FK (FK) and Fmoc-FKK (FKK), are synthesized. Through adjusting the component ratio of peptide and Dox, we obtain two kinds of co-assembled nanoparticles with homogeneous size distributions. These nanoparticles show several distinct characteristics. First, they are pH-responsive as they are stable in alkaline and neutral conditions, however, de-assembly at acidic pH enables selective Dox release in malignant cancer cells. Second, the nanoparticles show an average size of 50-100 nm with positive charges, making them effective for uptake by tumor cells. Moreover, the side effects of Dox on healthy cells are mitigated due to decreased exposure of free-Dox to normal cells. To conclude, the co-assembled peptide-Dox nanoparticles exhibit increased cellular uptake compared to free-Dox, therefore causing significant cancer cell death. Further apoptosis and cell cycle analysis indicates that there is a synergistic effect between the peptide and Doxorubicin.


Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Peptídeos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Fluorenos/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Tamanho da Partícula
11.
Anal Chim Acta ; 1098: 102-109, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31948572

RESUMO

Ratiometric analysis of dopamine (DA) in complex biological system is urgently desired. In this work, a novel dual-emission fluorescence probe was fabricated by embedding both gold nanoclusters (AuNCs) and poly(9,9-dioctylfluorenyl-2,7-diyl) (PFO) dots into zeolitic imidazolate framework-8 (ZIF-8) (abbreviated as ZIF-8@AuNCs-PFO) and applied to ratiometric analysis of DA. Remarkably, encapsulating AuNCs and PFO dots into ZIF-8 not only achieved an excellent aggregation induced emission (AIE) enhancement effect on AuNCs (5 times increase), but also brought about an unique DA-triggered asynchronous fluorescence changes of AuNCs and PFO dots. The as-prepared probe exhibited excellent performance toward DA in the concentrations range from 0.01 to 10000 µmol L-1 and good selectivity over interfering substances. The detection limit of DA was as low as 4.8 nmol L-1. Furthermore, good stability and practicability of the probe in human serum samples suggesting its great potential for diagnostic purposes. Moreover, the quenching mechanism of AuNCs was intensively studied and summarized as three synergistic processes: (i) electron transfer between AuNCs and DA; (ii) DA-triggered architecture change of ZIF-8; (iii) fluorescence resonance energy transfer (FRET) between AuNCs and polydopamine (PDA), which offered an important theory for ZIF-based fluorescent probes.


Assuntos
Dopamina/análise , Fluorenos/química , Corantes Fluorescentes/química , Ouro/química , Nanopartículas Metálicas/química , Pontos Quânticos/química , Zeolitas/química , Humanos , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
12.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936003

RESUMO

: A series of free base and Zn(II) phthalocyanines featuring fluorenyl antennae linked by methoxy or oxo bridges to the phthalocyanine core (Pc) were synthesized and characterized. Selected linear and nonlinear (two-photon absorption) optical properties of these new compounds were subsequently studied. As previously observed for related porphyrin dendrimers bearing 2-fluorenyl peripheral dendrons, an efficient energy transfer occurs from the peripheral antennae to the central phthalocyanine core following excitation in the fluorenyl-based π-π* absorption band of these chromophores. Once excited, these compounds relax to the ground state, mostly by emitting intense red light or by undergoing intersystem crossing. As a result, the tetrafunctionalized Zn(II) phthalocyanines are fluorescent, but can also efficiently photosensitize molecular oxygen in tetrahydrofurane (THF), forming singlet oxygen with nearly comparable yields to bare Zn(II) phthalocyanine (ZnPc). In comparison with the latter complex, the positive role of the fluorenyl-containing antennae on one- and two-photon brightness (2PA) is presently demonstrated when appended in peripheral (ß) position to the phthalocyanine core. Furthermore, when compared to known porphyrin analogues, the interest in replacing the porphyrin by a phthalocyanine as the central core to obtain more fluorescent two-photon oxygen photosensitizers is clearly established. As such, this contribution paves the way for the future development of innovative biphotonic photosensitizers usable in theranostics.


Assuntos
Fluorenos/química , Indóis/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Transferência de Energia , Fluorenos/síntese química , Indóis/síntese química , Luz , Luminescência , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fótons , Porfirinas/química , Oxigênio Singlete/isolamento & purificação , Análise Espectral
13.
Biosens Bioelectron ; 150: 111872, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740259

RESUMO

A strong hydroxide (OH-)-dependent ECL emission of carboxyl functionalized-poly (9,9-di-n-octylfluorenyl-2,7-diyl) polymer dots (PFO Pdots) was observed at +1.25 V, which is significantly stronger than the emission at +1.95 V reported in previous work. Moreover, hydrogen peroxide (H2O2) can efficiently quench OH--dependent ECL emission of PFO Pdots. Based on this discovery, a signal "off-on" ECL biosensing platform for microRNA-155 (miRNA-155) was developed. Firstly, PFO Pdots were modified onto the electrode to capture DNA duplex track-locker. In the presence of H2O2 in the test solution, the ECL signal of PFO Pdots was quenched to obtain a signal-off state. Subsequently, the DNA walker produced through the target miRNA-155-triggered catalytic hairpin assembly (CHA) walked along the DNA duplex track-locker to output amounts of G-rich short chain, forming a hemin/G-quadruplex. With the consumption of H2O2 by hemin/G-quadruplex, the ECL signal would be restored to a signal-on state, thus achieving an ultrasensitive detection of miRNA-155. The detection limit was low as 12.2 aM. Furthermore, our proposed biosensor demonstrated a tremendous selectivity and admirable stability, and exhibited a satisfactory performance for determinating intracellular miRNA-155. The integration of excellent ECL performance of PFO Pdots without any exogenous species or dissolved O2 as co-reactant and a highly efficient quenching effect of H2O2 on such an ECL emission will provide an attractive ECL platform for bioanalysis and clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Peróxido de Hidrogênio/química , MicroRNAs/isolamento & purificação , DNA/química , Fluorenos/química , Quadruplex G , Humanos , Hidróxidos/química , Limite de Detecção , MicroRNAs/química , Pontos Quânticos/química
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117887, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31818646

RESUMO

A simple colorimetric receptor was synthesized by the condensation of 2-amino fluorene with 2-hydroxy-5-nitrobenzaldehyde and its properties were investigated using colorimetric, fluorescence and DFT studies. The sensing mechanism was ascertained by 1H NMR titration studies. The synthesized receptor showed two-pronged chemosensing properties and exhibited remarkable colorimetric transitions from colorless to yellow in the presence of CN- and colorless to green in the presence of Cu2+ in 80:20 acetonitrile/water medium, which could be determined by naked eye observations. The detection limit of receptor to CN- and Cu2+ ion was found to be 7.9 × 10-7 M and 4.5 × 10-8 M respectively. Receptor was also successfully employed in the construction of molecular INHIBIT and YES logic gates. The synthesized receptor was also efficiently used for real-sample analysis in Finger Millet, also known as Ragi in Tamil. Its scientific name is Eleusine coracana.


Assuntos
Cobre/análise , Cianetos/análise , Teoria da Densidade Funcional , Fluorenos/química , Lógica , Ânions , Cátions , Cinética , Limite de Detecção , Conformação Molecular , Espectroscopia de Prótons por Ressonância Magnética , Receptores Artificiais/química , Espectrometria de Fluorescência
15.
J Chromatogr Sci ; 57(10): 910-919, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31644804

RESUMO

A new ultra-high-performance liquid chromatography method for the simultaneous quantification of sofosbuvir, daclatasvir and ledipasvir was developed. Two combinations of these direct-acting antivirals are used in hepatitis C virus infection therapy and show high efficacy and safety. Fractional factorial design was used for screening the most influential factors on separation and time analysis. These significant factors were optimized using a central composite design. The optimum resolution was carried out by using a Waters XBridge C18 column (150 mm, 4.6 mm ID, 5 µm) at a temperature of 35°C ± 2°C and acetonitrile/sodium perchlorate buffer (10 mM, pH = 3.2) (40: 60 v/v) as mobile phase at a flow rate of 1.5 mL min-1. UV detection was set at λ = 210 nm. A short chromatographic separation time was achieved. The developed method was validated according to the accuracy profile approach and was found specific, precise, faithful and accurate. The detection limits were between 0.07 and 0.13 µg mL-1. Hence, this novel method can be employed for the routine quality control analysis and in dissolution profile studies of generics containing these products.


Assuntos
Benzimidazóis/análise , Cromatografia Líquida de Alta Pressão/métodos , Fluorenos/análise , Imidazóis/análise , Sofosbuvir/análise , Benzimidazóis/química , Fluorenos/química , Imidazóis/química , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Sofosbuvir/química , Comprimidos
16.
Amino Acids ; 52(2): 199-211, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31520286

RESUMO

The polyamine (PA) metabolism is involved in cell proliferation and differentiation. Increased cellular PA levels are observed in different types of cancers. Products of PA oxidation induce apoptosis in cancer cells. These observations open a perspective to exploit the enzymes of PA catabolism as a target for anticancer drug design. The substances capable to enhance PA oxidation may become potential anticancer agents. The goal of our study was to explore how the mode of ligand binding with a PA catabolic enzyme is associated with its stimulatory or inhibitory effect upon PA oxidation. Murine N1-acetylpolyamine oxidase (5LFO) crystalline structure was used for molecular docking with ligands of various chemical structures. In vitro experiments were carried out to evaluate the action of the tested compounds upon PA oxidative deamination in a cell-free test system from rat liver. Two amino acid residues (Aps211 and Tyr204) in the structure of 5LFO were found to be significant for binding with the tested compounds. 19 out of 51 screened compounds were activators and 17 were inhibitors of oxidative deamination of PA. Taken together, these results enabled to construct a recognition model with characteristic descriptors depicting activators and inhibitors. The general tendency indicated that a strong interaction with Asp211 or Tyr204 was rather typical for activators. The understanding of how the structure determines the binding mode of compounds with PA catabolic enzyme may help in explanation of their structure-activity relationship and thus promote structure-based drug design.


Assuntos
Poliaminas/química , Poliaminas/metabolismo , Compostos de Anilina/química , Compostos de Anilina/metabolismo , Animais , Apoptose , Fluorenos/química , Fluorenos/metabolismo , Ligantes , Fígado/enzimologia , Simulação de Acoplamento Molecular , Oxirredução , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/química , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Piridinas/química , Piridinas/metabolismo , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
17.
Environ Geochem Health ; 42(8): 2485-2494, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264041

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) have been a major concern because of their carcinogenicity, mutagenicity, teratogenicity and wide distribution in the environment. Over 90% of PAHs in the environment exist on soil surface/sediment. Benzo[a]pyrene (BaP) is one of the predominant PAHs in soil. Thus, it is critically important to understand the patterns of BaP accumulation and transformation peculiarities in soil for the risk assessment. The studies were conducted in model experiment with Haplic Chernozem spiked with various doses of BaP (20, 200, 400 and 800 µg kg-1) equivalent to 1, 10, 20 and 40 levels of maximum permissible concentrations. The unique properties of Haplic Chernozem were studied allow to accumulate and transform BaP as well as barley plants ability to absorb of some BaP concentration. Extraction of BaP from the soil was carried out by the saponification method. The qualitative and quantitative determination of BaP and other polycyclic aromatic hydrocarbons (PAHs) was performed by high-performance liquid chromatography with fluorescence detection (Agilent 1260 Germany, 2014). BaP accumulation in soil depended on the applied BaP concentrations in Haplic Chernozem. Studying the features of PAHs transformation in the soil of a model experiment 1 year after the compound application showed the BaP content in the soil decreased up to 11-40%. Two years after the BaP application the content in the soil decreased up to 15-44% from the initial BaP content in the soil. The percentage of BaP concentration reduction in Haplic Chernozem increased with an increase in the dose of the applied xenobiotic. An increase in the dose of the applied pollutant to the soil of the model experiment contributed to an increase in all PAHs, which indicated a rapid BaP transformation in Haplic Chernozem. The PAHs content in the soils of model experiment in the first year of the research formed the following descending series: pyrene > chrysene > fluoranthene > phenanthrene. In the second year of research the phenanthrene content became higher than the fluoranthene content. The content of these compounds exceeded 20% of the total PAHs content in the soil samples in the first and second years of the model experiment. The features of PAHs accumulation and transformation in soils under artificial pollution showed the degradation of large-nuclear PAHs, starting from 5-ring polyarenes, and their structural reorganization into the less-nuclear polyarenes, such as 4-, 3-, and 2-ring PAHs. During the 2 years of the model experiment the BaP concentration in the soil decreased up to 15-44% from the initial BaP content in the soil.


Assuntos
Benzo(a)pireno/metabolismo , Poluentes do Solo/metabolismo , Benzo(a)pireno/química , Biodegradação Ambiental , Crisenos/química , Crisenos/metabolismo , Fluorenos/química , Fluorenos/metabolismo , Hordeum/metabolismo , Fenantrenos/química , Fenantrenos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Pirenos/química , Pirenos/metabolismo , Federação Russa , Solo/química , Poluentes do Solo/química
18.
Environ Geochem Health ; 42(8): 2471-2484, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31300942

RESUMO

In this study, determination of possible sources, soil-air exchange direction, and spatial distribution of PAH concentrations was aimed. In this scope, soil samples were collected from 35 different points, which have the urban and rural characteristics, from European and Asian Sides in Istanbul. The average ∑16PAH concentrations were found as 22.11 ng/g dw for urban site and 19.53 ng/g dw for rural site, respectively. The highest concentration was 279.5 ng/g dw. PAH concentrations were higher in urban site than rural site. Acenaphthene and benzo[k]fluoranthene were observed as the dominant species. PAH concentrations are observed higher mostly in north and west parts of European Side and south and east parts of Asian Side. There was net evaporation from soil to air for lower molecular weight PAHs with 2, 3 rings, while high molecular weight PAHs with 4, 5, 6 rings accumulated in the soil at both urban and rural sites. PAHs were mostly originated from coal burning and the use of diesel engine vehicles.


Assuntos
Poluentes Atmosféricos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes do Solo/análise , Acenaftenos/análise , Acenaftenos/química , Poluentes Atmosféricos/química , Cidades , Carvão Mineral/análise , Monitoramento Ambiental , Fluorenos/análise , Fluorenos/química , Hidrocarbonetos Policíclicos Aromáticos/química , Solo/química , Poluentes do Solo/química , Turquia
19.
Antiviral Res ; 174: 104678, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31862501

RESUMO

Approximately 71 million people suffer from hepatitis C virus (HCV) infection worldwide. Persistent HCV infection causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, resulting in approximately 400,000 deaths annually. Effective direct-acting antiviral agents (DAAs) have been developed and are currently used for HCV treatment targeting the following three proteins: NS3/4A proteinase that cleaves the HCV polyprotein into various functional proteins, RNA-dependent RNA polymerase (designated as NS5B), and NS5A, which is required for the formation of double membrane vesicles serving as RNA replication organelles. At least one compound inhibiting NS5A is included in current HCV treatment regimens due to the high efficacy and low toxicity of drugs targeting NS5A. Here we report fluorene compounds showing strong inhibitory effects on GT 1b and 3a of HCV. Moreover, some compounds were effective against resistance-associated variants to DAAs. The structure-activity relationships of the compounds were analyzed. Furthermore, we investigated the molecular bases of the inhibitory activities of some compounds by the molecular docking method.


Assuntos
Antivirais/farmacologia , Fluorenos/farmacologia , Hepacivirus/efeitos dos fármacos , Antivirais/química , Fluorenos/química , Variação Genética , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/antagonistas & inibidores
20.
Molecules ; 25(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878329

RESUMO

The development of high performance optically pumped organic lasers operating in the deep blue still remains a big challenge. In this paper, we have investigated the photophysics and the optical gain characteristics of a novel fluorene oligomer functionalized by four triphenylamine (TPA) groups. By ultrafast spectroscopy we found a large gain spectral region from 420 to 500 nm with a maximum gain cross-section of 1.5 × 10-16 cm2 which makes this molecule a good candidate for photonic applications. Amplified Spontaneous Emission measurements (ASE) under 150 fs and 3 ns pump pulses have revealed a narrow emission at 450 nm with a threshold of 5.5 µJcm-2 and 21 µJcm-2 respectively. Our results evidence that this new fluorene molecule is an interesting material for photonic applications, indeed the inclusion of TPA as a lateral substituent leads to a high gain and consequently to a low threshold blue organic ASE.


Assuntos
Compostos de Anilina/química , Fluorenos/química , Luz , Luminescência , Sondas Moleculares/química , Fatores de Tempo
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