Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.410
Filtrar
1.
Curr Protoc Nucleic Acid Chem ; 80(1): e103, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31985895

RESUMO

This article describes chemical synthesis of 2'-fluorinated Northern methanocarbacyclic (2'-F-NMC) nucleosides and phosphoramidites, based on a bicyclo[3.1.0]hexane scaffold bearing all four natural nucleobases (U, C, A, and G), and their incorporation into oligonucleotides by solid-supported synthesis. This synthesis starts from commercially available cyclopent-2-en-1-one to obtain the fluorinated carbocyclic pseudosugar intermediate (S.13), which can be converted to the uridine intermediate by condensation with isocyanate, followed by cyclization, and to adenine and guanine precursors by microwave-assisted reactions. All four 2'-F-NMC phosphoramidites are synthesized from S.13 in a convergent approach, and the monomers are used for synthesis of 2'-F-NMC-modified oligonucleotides. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Preparation of fluorinated carbocyclic pseudosugar intermediate Basic Protocol 2: Preparation of 2'-F-NMC uridine and cytidine phosphoramidites Basic Protocol 3: Preparation of 2'-F-NMC adenosine phosphoramidite Basic Protocol 4: Preparation of 2'-F-NMC guanosine phosphoramidite Basic Protocol 5: Synthesis of oligonucleotides containing 2'-F-NMC.


Assuntos
Flúor/química , Nucleosídeos/síntese química , Oligonucleotídeos/química , Nucleosídeos/química , Compostos Organofosforados/química
2.
Chemistry ; 26(7): 1511-1517, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31867761

RESUMO

Solid-state 19 F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the 19 F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI)3 are representatives of an α-helix and a ß-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for 19 F NMR structure analysis.


Assuntos
Alcenos/química , Peptídeos Catiônicos Antimicrobianos/química , Membrana Celular/química , Espectroscopia de Ressonância Magnética , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/síntese química , Flúor/química , Conformação Proteica em alfa-Hélice , Coloração e Rotulagem/métodos
3.
J Colloid Interface Sci ; 559: 197-205, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31627143

RESUMO

Mesoporous silica nanoparticle (MSN) demonstrates great potentials as a loading platform for bactericidal agents, but may be limited by its application form of bulk or powder. Herein, we developed MSN surface-enriched composite membranes with remarkable photodynamic antimicrobial activities via a facile electrospinning method. The mixture of zein and polycaprolactone (PCL) was served as the polymeric matrix, while the methylene blue (MB) loaded MSN was modified by trichloro (1H, 1H, 2H, 2H-heptadecafluorodecyl) silane (THFS) and acted as reactive oxygen species (ROS) generator to exert their antimicrobial performances. Owing to its low surface energy, the fluorinated MSN tended to be enriched on the surface of the nanofiber, hence significantly enhancing the ROS generation. Moreover, benefiting from the surface enrichment of the fluorinated nanoparticles, the composite membrane displayed obvious surface hydrophobicity and exhibited discernible bacterial repellency. Subsequently, upon visible light (660 nm) irradiation, the composite membrane demonstrated remarkable photodynamic antibacterial activities against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) but without essential detrimental impacts on the mammalian cells. We envision that this self-enriched MSN composite membrane may find broad applications in bacterial infection-resistant areas.


Assuntos
Anti-Infecciosos/química , Azul de Metileno/química , Nanopartículas/química , Fotoquimioterapia/métodos , Dióxido de Silício/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fibroblastos/citologia , Flúor/química , Interações Hidrofóbicas e Hidrofílicas , Luz , Camundongos , Poliésteres/química , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Zeína/química
4.
Chem Commun (Camb) ; 55(98): 14717-14720, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31702759

RESUMO

The final step in the biosynthesis of l-carnitine in humans is catalysed by the 2-oxoglutarate and ferrous iron dependent oxygenase, γ-butyrobetaine hydroxylase (BBOX). 1H and 19F NMR studies inform on the BBOX mechanism including by providing evidence for cooperativity between monomers in substrate/some inhibitor binding. The value of the 19F NMR methods is demonstrated by their use in the design of new BBOX inhibitors.


Assuntos
Inibidores Enzimáticos/química , Espectroscopia de Ressonância Magnética , gama-Butirobetaína Dioxigenase/metabolismo , Betaína/análogos & derivados , Betaína/síntese química , Betaína/química , Betaína/metabolismo , Carnitina/biossíntese , Carnitina/síntese química , Carnitina/química , Carnitina/metabolismo , Desenho de Drogas , Inibidores Enzimáticos/síntese química , Flúor/química , gama-Butirobetaína Dioxigenase/antagonistas & inibidores
5.
J Steroid Biochem Mol Biol ; 195: 105477, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31541729

RESUMO

During our ongoing studies of vitamin D, we focused on the vitamin D3 side-chain 24-position, which is the major metabolic site of human CYP24A1. In order to inhibit the metabolism of vitamin D3, 24,24-difluorovitamin D3analogues are important candidates. In this paper, we report the practical introduction of the difluoro-unit to the 24-position to synthesize 24,24-difluoro-CD ring (1) and 24,24-difluoro-25-hydroxyvitamin D3 (2).


Assuntos
Calcitriol/análogos & derivados , Flúor/química , Vitaminas/química , Calcitriol/química
6.
Eur J Med Chem ; 182: 111666, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494476

RESUMO

Polycation carriers hold great potential in gene therapy. However, they usually suffer from obvious cytotoxicity and unsatisfactory transfection efficiency. In this report, a series of fluorobenzene substituted and thioacetal contained polycations (TAEA-S-xF) were prepared to explore novel alternatives for safe and efficient non-viral polymeric gene vectors. The reactive oxygen species (ROS)-responsive property of thioacetal moieties together with the fluorine effect were hope to bring the vector better performance in gene delivery process. These materials could efficiently condense DNA into nanoparticles with proper size and surface potential. The structure-activity relationship of these materials was systematically investigated, and the In vitro transfection results revealed that the amount of fluorine atoms on the linkage plays important role to ensure the transfection efficiency and serum tolerance. The ROS-responsive behavior was verified by NMR, gel electrophoresis experiment and dynamic light scattering (DLS) assay. Cytotoxicity assay results also suggest that these ROS-degradable polycations show good biocompatibility in response to higher ROS level in cancer cells. Among these fluorinated polymers, the one with the most fluorine atoms showed the best transfection efficiency, which was up to 54 times higher than polyethyleneimine (PEI) 25 kDa. Mechanism studies reveal that its better performance may come from good cellular uptake and endosome escape ability.


Assuntos
Técnicas de Transferência de Genes , Vetores Genéticos/química , Poliaminas/química , Polietilenoimina/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Flúor/química , Flúor/metabolismo , Vetores Genéticos/síntese química , Vetores Genéticos/metabolismo , Halogenação , Humanos , Estrutura Molecular , Células PC-3 , Poliaminas/síntese química , Poliaminas/metabolismo , Polietilenoimina/síntese química , Polietilenoimina/metabolismo , Relação Estrutura-Atividade
7.
Molecules ; 24(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487944

RESUMO

Monovalent NHC-nickel complexes bearing triarylphosphine, in which fluorine is incorporated onto the aryl groups, have been synthesized. Tris(3,5-di(trifluoromethyl)-phenyl)phosphine efficiently gave a monovalent nickel bromide complex, whose structure was determined by X-ray diffraction analysis for the first time. In the solid state, the Ni(I) complex was less susceptible to oxidation in air than the triphenylphosphine complex, indicating greatly improved solid-state stability. In contrast, the Ni(I) complex in solution can easily liberate the phosphine, high catalytic activity toward the Kumada-Tamao-Corriu coupling of aryl bromides.


Assuntos
Complexos de Coordenação/química , Flúor/química , Níquel/química , Fosfinas/química , Catálise , Cristalografia por Raios X , Teoria da Densidade Funcional , Modelos Moleculares , Modelos Teóricos , Conformação Molecular , Estrutura Molecular , Oxirredução
8.
Mater Sci Eng C Mater Biol Appl ; 103: 109752, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349420

RESUMO

This study focuses on the effect of Sr-, F-, and their co-doping on the structure, biodegradation, bioactivity and cytocompatibility of diopside-based scaffolds, using X-ray diffraction, Raman spectroscopy, field-emission scanning electron microscopy, Archimedes densitometry, inductively coupled plasma spectroscopy, pH-metry, and cell MTT assay. The structural characterization of the scaffolds confirmed the successful incorporation of the dopants into the ceramic. In addition, all the doped scaffolds presented higher apatite-forming ability levels in comparison to the undoped one, where the highest and the least impact of doping on bioactivity belonged to F- and co-doping, respectively. It was found that the biodegradation difference of the scaffolds in terms of principal ions and the chance of F-incorporation into precipitated apatite determine the bioactivity difference of the samples. Osteoblast-like MG-63 cells exhibited the highest and lowest compatibility to the Sr-doped and co-doped scaffolds, respectively. In summary, F- and Sr-doping offered the highest bioactivity and cytocompatibility, respectively, whereas co-doping presented the weakest behaviors comparatively.


Assuntos
Flúor/química , Ácido Silícico/química , Ácido Silícico/farmacologia , Estrôncio/química , Tecidos Suporte , Apatitas/química , Neoplasias Ósseas/patologia , Substitutos Ósseos , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Teste de Materiais , Microscopia Eletrônica de Varredura , Osteossarcoma/patologia , Análise Espectral Raman , Difração de Raios X
9.
Phys Chem Chem Phys ; 21(28): 15400-15407, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31271395

RESUMO

A biomimetic membrane formed by hybrid Janus dendrimers (JDs) which contain hydrogenated and fluorinated dendrons was explored by dissipative particle dynamics simulations. The JD membrane is bilayered and shows a bicontinuous morphology which is also observed in nano-sized dendrimersomes. The thickness of the dendrimersome is significantly less than that of the planar membrane. The co-assembly of lipids with JDs to develop a hybrid membrane was studied as well. Lipids tend to locate in the hydrocarbon domain of the bicontinuous structure of the JD-rich membrane, while 2-dimensional micelles of JDs float in the leaflet of the lipid-rich membrane. The microstructure of the hybrid membrane was quantified by interdigitation lengths in the hydrocarbon, fluorocarbon, and lipid domains. Finally, the influence of lipid concentration on lipid fluidity was examined in terms of lipid diffusivity, which is found to be closely associated with the membrane microstructure.


Assuntos
Dendrímeros/química , Flúor/química , Lipídeos/química , Membranas Artificiais , Simulação por Computador , Hidrogenação , Micelas
10.
Eur J Med Chem ; 178: 297-314, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31195171

RESUMO

A small number of fluorinated 7-phenyl-pyrroloquinolinone (7-PPyQ) derivatives was synthesized in an attempt to improve the metabolic stability of 3N-ethyl-7-PPyQ and 3N-benzoyl-7-PPyQ. The possible impacts of the fluorine-hydrogen isosterism on both biological activity and metabolic stability were evaluated. Introduction of a fluorine atom in the 2 or 3 position of the 7-phenyl ring yielded the 7-PPyQ derivatives 12, 13 and 15, which showed potent cytotoxicity (low micromolar and sub-nanomolar GI50s) both in human leukemic and solid tumor cell lines. None of them induced significant cell death in quiescent and proliferating human lymphocytes. Moreover, 12, 13 and 15 exhibited remarkable cytotoxic activity in the multidrug-resistant cell line CEMVbl100, suggesting that they are not substrates for P-glycoprotein. All compounds inhibited tubulin assembly and the binding of [3H]colchicine to tubulin, with the best activity occurring with compound 15. Mechanistic studies carried out on compound 12 indicated that it caused (a) a strong G2/M arrest; (b) apoptosis in a time- and concentration-dependent manner; (c) a significant production of ROS (in good agreement with the observed mitochondrial depolarization); (d) caspase-3 and poly (ADP-ribose) polymerase activation; and (e) a decrease in the expression of anti-apoptotic proteins. In vivo experiments in a murine syngeneic tumor model demonstrated that compounds 12 and 15 significantly reduced tumor mass at doses four times lower than that required for the reference compound combretastatin A-4 phosphate. Neither monofluorination of the 7-phenyl ring of 3N-ethyl-7-PPyQ nor replacement of the benzoyl function of 3N-benzoyl-7-PPyQ with a 2-fluorobenzoyl moiety led to any improvement in the metabolic stability.


Assuntos
Antineoplásicos/farmacologia , Flúor/farmacologia , Quinolonas/farmacologia , Moduladores de Tubulina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flúor/química , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Estrutura Molecular , Quinolonas/química , Quinolonas/metabolismo , Relação Estrutura-Atividade , Moduladores de Tubulina/química , Moduladores de Tubulina/metabolismo
11.
Molecules ; 24(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174409

RESUMO

The photocatalytic activities of reduced titanium dioxide (TiO2) materials have been investigated by measuring their ability to produce hydroxyl radicals under UV and visible light irradiation. Degussa P25 TiO2 was doped with nitrogen (N), fluorine (F), and/or phosphorus (P) and then subjected to surface modification employing a thermo-physicochemical process in the presence of reducing agent sodium borohydride (NaBH4). The reduced TiO2 materials were characterized by a number of X-ray, spectroscopic and imaging methods. Surface doping of TiO2 was employed to modulate the band gap energies into the visible wavelength region for better overlap with the solar spectrum. Hydroxyl radical generation, central to TiO2 photocatalytic water purification applications, was quantitated using coumarin as a trap under UV and visible light irradiation of the reduced TiO2 materials. At 350 nm irradiation, the yield of hydroxyl radicals generated by the reduced forms of TiO2 was nearly 90% of hydroxyl radicals generated by the Degussa P25 TiO2. Hydroxyl radical generation by these reduced forms of TiO2 was also observed under visible light irradiation (419 and 450 nm). These results demonstrated that simple surface modification of doped TiO2 can lead to visible light activity, which is important for more economical solar-driven applications of TiO2 photocatalysis.


Assuntos
Radical Hidroxila/química , Processos Fotoquímicos , Titânio/química , Flúor/química , Radical Hidroxila/efeitos da radiação , Luz , Nitrogênio/química , Fósforo/química , Titânio/efeitos da radiação , Raios Ultravioleta
12.
J Chromatogr A ; 1601: 86-94, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31235331

RESUMO

Effective extraction is an indispensable procedure for the sensitive analysis of fluoroquinolones (FQs) in complex samples. According to the molecular properties of FQs, a new highly fluorinated and boron-rich adsorbent (FBA) was synthesized and employed as the extraction phase of magnetic solid-phase extraction (MSPE). Results revealed that the prepared FBA displayed satisfactory extraction capability for FQs through fluorophilic and B-N coordination interactions. Besides, the synthesized FBA also exhibited strong magnetic responsiveness and good life-span. Under the most favorable conditions, the FBA/MSPE was combined with high-performance liquid chromatography with diode array detection (HPLC-DAD) to sensitively quantify trace levels of FQs in environmental water and milk samples. The developed approach showed good linearity within the studied concentration range, satisfactory precision and low limits of detection (0.0049-0.016 µg/L for water sample and 0.010-0.046 µg/kg for milk sample). In the analysis of target FQs in real samples, the recoveries of different fortified concentrations were in the ranges of 80.1-120% and 78.9-119% for water and milk samples, respectively. The relative standard deviations for reproducibility were all below 11%. The results well evidence that the introduced FBA/MSPE is a promising extraction technology for FQs, and the established FBA/MSPE-HPLC/DAD approach is suitable to measure low concentrations of FQs in water and milk samples.


Assuntos
Monitoramento Ambiental/métodos , Fluoroquinolonas/isolamento & purificação , Análise de Alimentos/métodos , Magnetismo , Leite/química , Extração em Fase Sólida , Água/análise , Animais , Boro/química , Cromatografia Líquida de Alta Pressão , Flúor/química , Fluoroquinolonas/análise , Reprodutibilidade dos Testes , Poluentes Químicos da Água/análise
13.
Eur J Pharm Biopharm ; 142: 114-122, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220572

RESUMO

BACKGROUND: Perfluorocarbon (PFC)-nanoemulsions (NE) are a convenient tool for 19F magnetic resonance imaging in cell and animal experiments. Typical preparation methods, like high-pressure homogenization or microfluidization, produce nanoemulsions in mL-scale. However, experiments usually require only miniscule amounts of PFC-NE, several 100 µL. For site-specific imaging tissue-specific ligands, e.g. peptides or antibodies, are covalently bound to the NE surface. This requires the use of expensive functionalized phospholipids containing reactive groups (e.g. maleimide), which often deteriorate quickly in liquid storage, rendering the manufacturing process highly cost-inefficient. A technique to manufacture storage stable NE that maintain their functionality for coupling of various ligands is desired. METHODS AND RESULTS: Different PFC-NE formulations and preparation techniques were compared and the most suitable of these was tested in short-, as well as long-term stability tests. Droplet size stability was investigated by dynamic light scattering and cryogenic transmission electron microscopy over 1.5 a. Surface modifiability was assessed by a fluorescence assay. The utility of these NE was proven in an in vitro model. CONCLUSION: The established PFC-NE platform offers a cost-efficient way to produce larger amounts of long-term storable imaging agents, which can be surface-modified on demand for application in targeted 19F MRI.


Assuntos
Emulsões/química , Flúor/química , Fluorcarbonetos/química , Nanopartículas/química , Nanoestruturas/química , Meios de Contraste/química , Difusão Dinâmica da Luz/métodos , Humanos , Imagem por Ressonância Magnética/métodos , Microscopia Eletrônica de Transmissão/métodos , Tamanho da Partícula
14.
Chirality ; 31(8): 603-615, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31222828

RESUMO

In this study, a series of fluorine-containing chiral hydrazide-hydrazone derivatives [III-XII] from ʟ-cysteine ethyl ester hydrochloride was synthesized as new antioxidant and anticholinesterase agents. The antioxidant activity of these derivatives was evaluated by ABTS+· and DPPH· scavenging and CUPRAC assays and the anticholinesterase activity by the Ellman method spectrophotometrically. The results of the antioxidant assay showed that compounds V, IX, and X exhibited higher activity than BHT and α-tocopherol used as positive standards. Among the synthesized derivatives, compound IX (IC50 : 2.3 ± 1.6 µM) exhibited higher acetylcholinesterase inhibitory activity than galantamine (IC50 : 4.5 ± 0.8 µM). Compounds XI (IC50 : 9.6 ± 1.0 µM), IX (IC50 : 12.5 ± 1.6 µM), III (IC50 : 16.0 ± 1.6 µM), X (IC50 : 17.2 ± 1.8 µM), VI (IC50 : 20.2 ± 0.8 µM), XII (IC50 : 21.5 ± 1.0 µM), and VII (IC50 : 24.6 ± 0.6 µM) displayed better butyrylcholinesterase inhibitory activity than galantamine (IC50 : 46.03 ± 0.14 µM). ADME-Tox analysis was used to probe the drug-like properties of the compounds. Molecular docking studies were also applied to understand the interactions between compounds and targets. The docking calculations were supported by the experimental data. In particular, compound IX, having better activity than galantamine against acetylcholinesterase and butyrylcholinesterase enzymes, was visualized using molecular docking.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Flúor/química , Animais , Antioxidantes/síntese química , Antioxidantes/farmacocinética , Barreira Hematoencefálica/efeitos dos fármacos , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacocinética , Simulação por Computador , Desenho de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Hidrazinas/química , Hidrazonas/química , Absorção Intestinal/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Espectrofotometria Ultravioleta
15.
Dalton Trans ; 48(20): 6910-6920, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31038129

RESUMO

In order to address outstanding questions about ruthenium complexes in complex biological solutions, 19F NMR spectroscopy was used to follow the binding preferences between fluorinated RuII(η6-arene)(bipyridine) complexes and protected amino acids and glutathione. Reporting what ruthenium compounds bind to in complex environments has so far been restricted to relatively qualitative methods, such as mass spectrometry and X-ray spectroscopic methods; however, quantitative information on the species present in the solution phase cannot be inferred from these techniques. Furthermore, using 1H NMR, in water, to distinguish and monitor a number of different complex RuII(η6-arene) adducts forming is challenging. Incorporating an NMR active heteroatom into ruthenium organometallic complexes provides a quantitative, diagnostic 'fingerprint' to track solution-phase behaviour and allow for unambiguous assignment of any given adduct. The resulting 19F NMR spectra show for the first time the varied, dynamic behaviour of organoruthenium compounds when exposed to simple biomolecules in complex mixtures. The rates of formation of the different observed species are dramatically influenced by the electronic properties at the metal, even in a closely related series of complexes in which only the electron-donating properties of the arene ligand are altered. Preference for cysteine binding is absolute: the first quantitative solution-phase evidence of such behaviour.


Assuntos
Aminoácidos/análise , Complexos de Coordenação/química , Flúor/química , Rutênio/química , Complexos de Coordenação/síntese química , Cisteína/química , Halogenação , Cinética , Ligantes , Estrutura Molecular , Água/química
16.
Molecules ; 24(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064070

RESUMO

Control over spin states at the single molecule level is a key issue in the emerging field of molecular spintronics. Here, we explore the chemical adsorption effect on the magnetic and spin-transport properties of individual magnetic molecule by performing extensive density functional theory calculations in combining with non-equilibrium Green's function method. Theoretical results clearly reveal that the molecular magnetic moment of Mn-salophen can be effectively tuned by adsorbing F and CO on the central Mn cation, while the adsorbed NO molecule quenches the molecular magnetic moment. Without chemical adsorption, the currents through Mn-salophen molecular junction just show a little distinction for two spin channels, which agrees well with previous investigation. Remarkably, the conductive channel can be switched from the spin-up electrons to the spin-down electrons via adsorbing F and CO, respectively, and the corresponding two Mn-salophen molecular junctions with chemical modifications display nearly perfect spin-filtering effect. The observed spin switch and the predicted spin-filtering effect via chemical adsorption indicates that Mn-salophen holds potential applications in molecular spintronic devices.


Assuntos
Complexos de Coordenação/química , Manganês/química , Salicilatos/química , Adsorção , Monóxido de Carbono/química , Simulação por Computador , Condutividade Elétrica , Elétrons , Flúor/química , Ligantes , Magnetismo/métodos , Modelos Químicos , Estrutura Molecular , Fenômenos Físicos , Relação Estrutura-Atividade
17.
Molecules ; 24(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064095

RESUMO

Apart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor drugs, enhancing their in vitro and in vivo cytotoxicity. The permutation of hydrophilic and hydrophobic aryl groups in COX inhibitors leads to cardinal changes in the biological activity of the compounds. In the present study, thirteen heterocyclic coxib-like 4,5-diarylfuran-3(2H)-ones and their annelated derivatives-phenanthro[9,10-b]furan-3-ones-were synthesized and studied for anti-inflammatory and COX-1/2 inhibitory action and for their cytotoxic activity on the breast cancer (MCF-7) and squamous cell carcinoma (HSC-3) cell lines. The F-derivative of the -SOMe substituted furan-3(2H)-ones exhibited the best activity (COX-1 IC50 = 2.8 µM, anti-inflammatory activity (by carrageenan paw edema model) of 54% (dose 0.01 mmol/kg), and MCF-7 and HSC-3 cytotoxicity with IC50 values of 10 µM and 7.5 µM, respectively). A cytotoxic effect related to the COX-1 inhibitory action was observed and a synergistic effect with the anti-neoplastic drugs gefitinib and 5-fluorouracil was found. A phenanthrene derivative exhibited the best synergistic effect with gefitinib.


Assuntos
Furanos/química , Furanos/farmacologia , Sequência de Aminoácidos , Aminoácidos/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Carragenina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Drogas , Edema/metabolismo , Flúor/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
18.
Chemistry ; 25(51): 11797-11819, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31099931

RESUMO

Over the last two decades, fluorine substitution has become one of the essential structural traits in modern pharmaceuticals. Thus, about half of the most successful drugs (blockbuster drugs) contain fluorine atoms. In this review, we profile 17 fluorine-containing drugs approved by the food and drug administration (FDA) in 2018. The newly approved pharmaceuticals feature several types of aromatic F and CF3 , as well as aliphatic (CF2 ) substitution, offering advances in the treatment of various diseases, including cancer, HIV, malarial and smallpox infections.


Assuntos
Flúor/farmacologia , Flúor/química , Humanos , Estados Unidos , United States Food and Drug Administration
19.
Pharm Res ; 36(7): 105, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31102031

RESUMO

PURPOSE: To reveal the underlying mechanism inducing the opposite trends of surface composition enrichment of spray dried amorphous solid dispersions (ASD) of sorafenib and regorafenib, two compounds only differ in hydrogen to fluorine substitution. METHODS: Sorafenib/PVP and regorafenib/PVP ASDs were prepared by spray drying. Morphology of ASDs was visually inspected and examined by SEM. The surface compositions of ASDs were analyzed by XPS. Glass transition temperature (Tg) of ASDs was determined by DSC. Water vapor sorption isotherms of ASDs were studied by moisture sorption analyzer. Molecular interaction between the drug and the polymer was analyzed by solution NMR. RESULTS: In 10% and 20% drug loading sorafenib/PVP ASDs, short time moisture exposure induced PVP enrichment on the surface, and the appearance of initial ASDs powder became gel-like after water uptake. While in 30% sorafenib/PVP and any regorafenib/PVP ASDs regardless of drug loading, moisture exposure induced surface drug enrichment, while their powder-like appearance and average particle size remained unchanged. Meanwhile, sorafenib/PVP had similar water vapor sorption isotherms as regorafenib/PVP, before and after moisture induced phase separation. NMR study demonstrated a hex atomic ring H-bonding interaction between the drug and PVP, with a 1:1 drug: monomer stoichiometry molar ratio, which persisted in sorafenib/PVP but not regorafenib/PVP system under 95%RH moisture. CONCLUSIONS: Moisture exposure could lead to drug or polymer enrichment on the surface of ASDs, while the viability of drug-polymer interaction persisting in water environment contributed to such surface composition enrichment.


Assuntos
Flúor/química , Hidrogênio/química , Sorafenibe/química , Umidade , Transição de Fase , Compostos de Fenilureia/química , Polímeros/química , Povidona/química , Piridinas/química , Solubilidade , Vapor , Propriedades de Superfície
20.
Molecules ; 24(8)2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-31009999

RESUMO

Organofluorine compounds are finding increasing application in a variety of fields such as pharmaceutical, agrochemical, and material sciences. However, given the scarcity of fluorine-containing natural products, advancement in this area depends almost entirely on the development of new synthetic methodologies. In this article, we present the synthesis of a series of previously undescribed (E)-ß-fluorovinyl sulfones via a simple copper-catalyzed addition of hydrogen fluoride to alkynyl sulfone starting materials in varying yields and E/Z selectivities. The hydrogenation of these products was also explored and compared with the hydrogenation of the related Z isomers. These new products may find interesting applications, given the versatility of vinyl sulfones in chemical synthesis and the unique properties of vinyl fluorides in biological settings.


Assuntos
Flúor/química , Compostos de Vinila/química , Catálise , Cobre/química , Hidrogenação , Estrutura Molecular , Compostos de Vinila/síntese química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA