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1.
Chem Commun (Camb) ; 56(1): 125-128, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31793952

RESUMO

We compare the ability of a prototypical dicarboxylic acid and its fluorinated analogue to act as molecular building blocks for the formation of self-assembled monolayers. Whilst fluorination is found to prevent homomolecular self-assembly, it greatly increases the ability of the carboxylic acid to act as a hydrogen bond donor for the formation of bimolecular networks.


Assuntos
Fluorbenzenos/química , Ácidos Ftálicos/química , Piridinas/química , Triazinas/química , Halogenação , Ligações de Hidrogênio
2.
Chemosphere ; 239: 124793, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726530

RESUMO

Developing an efficient and environmentally friendly strategy for oil-water separation is extremely important for practical application. In this study, a superhydrophobic and superoleophilic melamine sponge loaded with cross-linked and swellable polydivinylbenzene was successfully fabricated by a facile and effective one-step impregnation-curing method with adhesion of polydimethylsiloxane. The prepared sponge not only exhibited high oil absorption capacity, but it also enabled rapid oil collection in situ, which could be extended to practical application. Moreover, the modified superhydrophobic sponge showed excellent mechanical resistance and chemical stability. The surface morphology and chemical composition were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. This material has great development potential for large-scale oil spill clean-up and chemical spill accidents.


Assuntos
Dimetilpolisiloxanos/química , Recuperação e Remediação Ambiental/métodos , Óleos/química , Poluição por Petróleo/análise , Polivinil/química , Triazinas/química , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Nanoporos , Espectroscopia Fotoeletrônica , Polímeros/química , Água/química
3.
Eur J Med Chem ; 185: 111804, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675510

RESUMO

The emergence of drug resistance has created unmet medical need for the development of new classes of antibiotics. Innovation of new antibacterial agents with new mode of action remains a high priority universally. Triazines are six-membered, nitrogen-containing heterocyclic scaffold with a wide range of pharmaceutical properties such as antibacterial, antifungal, anticancer, antioxidants, antitubercular, antimalarial, anti-HIV, anticonvulsant, anti-inflammatory, antiulcer, and analgesic activities. The present review focuses on the recent developments in the area of medicinal chemistry to discover various chemical structures as potential antimicrobial agents and their structure-activity relationships (SAR) studies are also discussed for further rational design of this kind of derivatives.


Assuntos
Antibacterianos/farmacologia , Antivirais/farmacologia , Bactérias/efeitos dos fármacos , Triazinas/farmacologia , Vírus/efeitos dos fármacos , Antibacterianos/química , Antivirais/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Triazinas/química
4.
J Sci Food Agric ; 100(1): 301-307, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525264

RESUMO

BACKGROUND: Cyromazine (CYR) and its main degradation product melamine (MEL) are attracting wide attention due to their potential hazards to the environment and humans. In this work, double surfactants-assisted electromembrane extraction (DS-EME) by Tween 20 and alkylated phosphate was firstly used for purification and extraction of CYR and MEL, and the extract was directly analyzed by capillary electrophoresis with capacitively coupled contactless conductivity detection. RESULTS: Under the optimum conditions, two targets could be well separated from the main interferences, including common biogenic amines and inorganic cations within 14 min. This developed method was successfully applied to the analyses of surface water, soil and cucumber samples, and the average recoveries were in the range 93.3-112%. DS-EME provided a synergistic purification and enrichment effect for CYR and MEL by adding Tween 20 and alkylated phosphate into donor phase and supporting liquid membrane, respectively. Satisfactory limits of detection [0.2-1.5 ng mL-1 , signal-to-noise ratio (S/N) = 3] could be obtained in the tested sample matrices, and the corresponding enrichment factors were up to 115∼123 times. CONCLUSION: This developed method provides an alternative for the simultaneous analysis of CYR and MEL in complex real-world samples. © 2019 Society of Chemical Industry.


Assuntos
Cucumis sativus/química , Poluentes do Solo/isolamento & purificação , Extração em Fase Sólida/métodos , Triazinas/isolamento & purificação , Poluentes da Água/isolamento & purificação , Condutividade Elétrica , Eletroforese Capilar , Membranas Artificiais , Poluentes do Solo/química , Extração em Fase Sólida/instrumentação , Tensoativos/química , Triazinas/química , Poluentes da Água/química
5.
Chemosphere ; 238: 124691, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524626

RESUMO

In recent years, forward osmosis (FO) has represented numerous potential applications in safe water production. In this study, we improved the performance of FO thin film composite (TFC) membranes for the removal of trace organic compounds (TOrCs) by tuning the chemistry of its top active layer. The TFC membranes were synthesized by interfacial polymerization (IP) reaction between amine-containing monomers, e.g., meta-phenylene diamine (MPD) or para-phenylenediamine (PPD), and an acid chloride monomer, e.g., trimesoyl chloride (TMC). Owing to three free amine functionals over main core, melamine was used in the amine monomers solution to increase cross-linking among polyamide chains. Chemical and morphological characterization of the prepared membranes confirmed that melamine was successfully incorporated into the chemical structure of the top PA layer. Two agricultural toxic materials (atrazine and diazinon) were used to investigate the capability of the newly fabricated membranes in the removal of TOrCs. The obtained results showed that melamine-improved FO membranes provided higher atrazine and diazinon rejections in two different FO membrane configurations, including active layer facing feed solution (ALF) and active layer facing draw solution (ALD). The highest rejections of both diazinon (99.4%) and atrazine (97.3%) were achieved when the melamine modified MPD-based membrane served in ALF mode with 2 M NaCl as a draw solution.


Assuntos
Substâncias Húmicas/análise , Osmose/fisiologia , Purificação da Água/instrumentação , Purificação da Água/métodos , Atrazina/análise , Diazinon/análise , Membranas Artificiais , Nylons/química , Fenilenodiaminas/química , Polimerização , Cloreto de Sódio/química , Triazinas/química , Ácidos Tricarboxílicos/química , Água/química
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117352, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31344580

RESUMO

The detection and filtration of melamine in food products has become an emergence due to its harmful effect on humans. In present work, we have investigated the binding mechanism of melamine over carboxyl group edge-functionalized graphene quantum dots doped with oxygen and sulphur atoms (O-GQD and S-GQD). In order to monitor melamine, surface enhanced Raman scattering (SERS) is adopted which is an effective vibrational spectroscopic approach. Electronic and vibrational properties were analysed by means of well adapted density functional theory (DFT). The calculated adsorption energy of melamine over O-GQD and S-GQD is -1.18 and -0.15 eV respectively. The characteristic peak of melamine at 688 cm-1 is in good agreement with previously reported experimental work and enhances by 348.4% in SERS spectra of Mel-O-GQD and 48% in SERS spectra of Mel-S-GQD. We have calculated the chemical enhancement factor (EF) for melamine over O-GQD and S-GQD and found the enhancement of 4.51 and 1.48 which is greater than melamine­silver complexes. Our theoretical studies on SERS of melamine over O-GQD and S-GQD suggest that oxygen is a better candidate for SERS. Our work demonstrates that the graphene quantum dots are remarkable platforms for the detection of melamine.


Assuntos
Grafite/química , Pontos Quânticos/química , Análise Espectral Raman/métodos , Triazinas/análise , Oxigênio/química , Triazinas/química
7.
Analyst ; 144(22): 6641-6646, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31595888

RESUMO

The detection of the HPV L1 protein provides information about the infection status of the virus, reflects the replication status of the HPV virus in cervical cells, and helps understand the regression and progress of cervical lesions. Herein, we report a novel laser desorption ionization mass spectrometry (LDI MS) method for the sensitive detection of the HPV 16 L1 protein, based on non-covalent competitive adsorption between the HPV 16 L1 aptamer and melamine on gold nanoparticles (AuNPs). The intensity of the MS signal corresponding to the mass tag shows a linear relationship with the HPV 16 L1 concentration in the range 2-80 ng mL-1, with a limit of detection (LOD) of 58.8 pg mL-1. Using this method, the HPV 16 L1 protein is quantitatively analyzed in both clinical and vaccine samples. The described method is simple and has high sensitivity and good reliability.


Assuntos
Proteínas do Capsídeo/análise , Nanopartículas Metálicas/química , Proteínas Oncogênicas Virais/análise , Adsorção , Aptâmeros de Nucleotídeos/química , Sequência de Bases , Proteínas do Capsídeo/química , Ouro/química , Papillomavirus Humano 16/química , Limite de Detecção , Espectrometria de Massas/métodos , Proteínas Oncogênicas Virais/química , Vacinas contra Papillomavirus/análise , RNA/química , Triazinas/química
8.
Ecotoxicol Environ Saf ; 185: 109702, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31585394

RESUMO

The purpose of our work was to determine the acute and chronic toxicity of three of the EU's most common herbicides - mesotrione, S-metolachlor, terbuthylazine - and their mixtures by Aliivibrio fischeri ecotoxicological assays. While comparing the sensitivity of the acute (30 min) Microtox® standard assay with the chronic (25 h) test adapted to microtiter plate, joint effects (antagonism, additive effect and synergism) to the bioluminescence inhibition (consequently the metabolic damage) in A. fischeri were also determined by Combination Index (CI) method. 30 min of exposure to mesotrione and S-metolachlor resulted in a relatively low acute toxicity (EC50 values were 118 and 265 mg/L), while terbuthylazine did not cause bioluminescence inhibition at all. Results showed that the chronic toxicity of S-metolachlor and terbuthylazine to A. fischeri (EC5010h = 59.2 and 4.9 mg/L and EC5015h = 54.0 and 9.6 mg/L, respectively) is larger by at least one order of magnitude than that after 30 min of contact time. Considering mesotrione no significant difference was experienced in toxicity. Regarding the EC50 values, all of the mixtures had synergistic joint effects in the acute assay. However, in the chronic test all the mixtures showed antagonistic responses with the exception of mesotrione and S-metolachlor (ratio 1:1) combination, which also had additive and synergistic effects after 10 and 15 h of exposure, similarly to the short-term test. This is also the first report of the joint effects of these herbicides. The chronic test is a more sensitive indicator to the active ingredients; both acute and chronic assays supply valuable data of the toxic properties of the pesticides. Moreover, the short- and long-term joint effects of their mixtures supporting a more accurate and reliable risk assessment.


Assuntos
Acetamidas/toxicidade , Aliivibrio fischeri/efeitos dos fármacos , Cicloexanonas/toxicidade , Herbicidas/toxicidade , Triazinas/toxicidade , Poluentes Químicos da Água/toxicidade , Acetamidas/química , Bioensaio , Cicloexanonas/química , Relação Dose-Resposta a Droga , Ecotoxicologia , Herbicidas/química , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Triazinas/química , Poluentes Químicos da Água/química
9.
Mater Sci Eng C Mater Biol Appl ; 104: 109975, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500037

RESUMO

Sulfonated melamine-formaldehyde including iron oxide nanoparticles were synthesized by sulfonation of melamine-formaldehyde and then Fe3O4 nanoparticles were bounded onto the surface of sulfonated melamine-formaldehyde (SMF). Two different iron oxide nanostructures including nanorods/spheres and nanospheres on sulfonated melamine-formaldehyde (SMF/Fe3O4) were obtained only by modifying the time of radiation from 4 to 8 h in our synthetic method. Furthermore core/shell (Fe3O4@SMF) was prepared by entrapping Fe3O4 magnetic nanoparticles as the core and sulfonated melamine-formaldehyde as the outer shell. The prepared components were characterized via, Fourier transform infrared spectroscopy (FT-IR), titration, X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) analysis, Barret-Joyner-Halenda (BJH) analysis, vibrating sample magnetometer (VSM), energy-dispersive X-ray (EDX) spectroscopy, and thermal gravimetric analysis (TGA). According to obtained results, the synthesized products had a thermal stability near 180 °C, particle-size distribution around of 20-140 nm and surface area between 6 and 10 m2/g. In this study, vapor was used as a heat source. These effective and magnetically recoverable catalysts were employed for the synthesis of numerous 3,4-dihydropyrimidin-2(1H)-ones by utilizing aldehydes, ethylacetoacetate and urea. Functional easiness, excellent yields, short reaction time, the simplicity of work-up or filter, and thermal stability of these catalysts created them as appropriate heterogeneous systems and acceptable alternative to different heterogeneous catalysts.


Assuntos
Compostos Férricos/química , Nanotubos/química , Triazinas/química , Catálise/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Magnetismo/métodos , Nanopartículas de Magnetita/química , Nanopartículas/química , Nanoestruturas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Inquéritos e Questionários , Ultrassom/métodos , Difração de Raios X/métodos
10.
Eur J Med Chem ; 183: 111641, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514062

RESUMO

Cyclin dependent kinase 7 (CDK7) plays a double role as it activates several other cyclin dependent kinases and participates to the initiation of transcription. This kinase is overexpressed in various types of tumors. Relatively few selective CDK7 inhibitors have been up to now disclosed. Most of these inhibitors belong to two chemical families: pyrazolopyrimidines and pyrazolotriazines on one side and pyrimidines on another side. They also differ by their molecular mechanism of action. Some are acting as competitive inhibitors and some others are covalent inhibitors. With these tools, the understanding of the potential therapeutic interest of CDK7 inhibitors in cancer is rapidly growing. They display antiproliferative activity against various types of tumors and leukemia and synergies have been identified. Two inhibitors are undergoing clinical testing. The most potent compounds inhibit a large number of cell-lines with IC50 < 200 nM.


Assuntos
Antineoplásicos/química , Quinases Ciclina-Dependentes/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Pirimidinas/química , Triazinas/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desenvolvimento de Medicamentos , Humanos , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Triazinas/farmacologia
11.
Sensors (Basel) ; 19(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491964

RESUMO

The globalization of food distribution has made necessary to secure safe products to the general consumers through the rapid detection of harmful additives on the field. For this purpose, we developed a cuvette-type localized surface plasmon resonance (LSPR) sensor that can be easily used by consumers with conventional ultraviolet-visible light spectrophotometer for in-situ measurements. Gold nanoparticles were uniformly deposited on a transparent substrate via a self-assembly method to obtain a plasmonically active chip, and the chemical receptor p-nitroaniline (p-NA) was functionalized to stabilize the device sensitivity under external temperature and pH conditions. The fabricated chip was fixed onto a support and combined with a cuvette-type LSPR sensor. To evaluate the applicability of this sensor on the field, sensitivity and quantitative analysis experiments were conducted onto melamine as a model sample from harmful food additives. Under optimal reaction condition (2 mM p-NA for 20 min), we achieved an excellent detection limit (0.01 ppb) and a dynamic range allowing quantitative analysis over a wide concentration range (0.1-1000 ppb) from commercially available milk powder samples.


Assuntos
Técnicas Biossensoriais , Fórmulas Infantis/química , Triazinas/isolamento & purificação , Animais , Ouro/química , Humanos , Lactente , Limite de Detecção , Nanopartículas Metálicas/química , Ressonância de Plasmônio de Superfície , Triazinas/química
12.
Anal Chim Acta ; 1082: 176-185, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472706

RESUMO

We report herein a novel multiple electrochemical aptasensor based on covalent-organic framework (COF) for sensitive and simultaneous detection of miRNA 155 and miRNA 122, by using shell-encoded gold nanoparticles (Au NPs) as signal labels (AgNCs@AuNPs and Cu2O@AuNPs, respectively, NCs = nanoclusters). A new COF nanowire was synthesized via condensation polymerization of 1,3,6,8-tetra(4-carboxylphenyl)pyrene and melamine (represented by TBAPy-MA-COF-COOH) for multiple aptasensor fabrication. The nanowire was then used as a platform for anchoring single-strand DNA (ssDNA), which was hybridized with the complementary aptamer (cApt) probes of miRNA 155 and miRNA 122. AgNCs@AuNPs and Cu2O@AuNPs modified with cApts show separated differential pulse voltammetry (DPV) peaks at 0.08 and -0.1 V, respectively. The signal labels immobilized with cApts were released from the hybridized DNA complex and bound to their corresponding targets when contacting miRNAs. This phenomenon results in the substantial decline of the DPV peak current density of the signal labels. The developed TBAPy-MA-COF-COOH-based aptasensor has superior performance for sensing miRNA 155 and miRNA 122 simultaneously, with ultrasensitive low detection limits of 6.7 and 1.5 fM (S/N = 3), respectively, a wide linear range of 0.01-1000 pM, and high selectivity and applicability for serum samples. The proposed TBAPy-MA-based aptasensor demonstrates potential for simultaneous detection of multiple cancer biomarkers by replacing other ssDNA and aptamer strands.


Assuntos
Nanopartículas Metálicas/química , MicroRNAs/sangue , Nanofios/química , Polímeros/química , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Técnicas Biossensoriais/métodos , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Ouro/química , Humanos , Limite de Detecção , Hibridização de Ácido Nucleico , Pirenos/química , Reprodutibilidade dos Testes , Triazinas/química
13.
Chemistry ; 25(58): 13275-13279, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31398268

RESUMO

Manipulation of the emerging anion-π interactions in a highly cooperative manner through sophisticated host design represents a very challenging task. In this work, unprecedented tetrahedral anion-π receptors have been successfully constructed for complementary accommodation of tetrahedral and relevant anions. The synthesis was achieved by a macrocycle-directed approach by using large macrocycle precursors bearing four reactive sites, which enabled a kinetic-favored pathway and afforded the otherwise inaccessible tetrahedral cages in considerable yields. Crystal structure suggested that the tetrahedral cages have an enclosed three-dimensional cavity surrounded by four electron-deficient triazine faces in a tetrahedral array. The complementary accommodation of a series of tetrahedral and relevant anions including BF4 - , ClO4 - , H2 PO4 - , HSO4 - , SO4 2- and PF6 - was revealed by ESI-MS and DFT calculations. Crystal structures of ClO4 - and PF6 - complexes showed that the anion was nicely encapsulated within the tetrahedral cavity with up to quadruple cooperative anion-π interactions by an excellent shape and size match. The strong anion-π binding was further confirmed by negative ion photoelectron spectroscopy measurements.


Assuntos
Compostos Macrocíclicos/química , Triazinas/química , Ânions/química , Boratos/química , Reagentes para Ligações Cruzadas/química , Cristalização , Teoria da Densidade Funcional , Estrutura Molecular , Percloratos/química , Espectrometria de Massas por Ionização por Electrospray , Sulfatos/química
14.
Molecules ; 24(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370274

RESUMO

Phosphodiesterase 2A (PDE2A) is highly expressed in distinct areas of the brain, which are known to be related to neuropsychiatric diseases. The development of suitable PDE2A tracers for Positron Emission Tomography (PET) would permit the in vivo imaging of the PDE2A and evaluation of disease-mediated alterations of its expression. A series of novel fluorinated PDE2A inhibitors on the basis of a Benzoimidazotriazine (BIT) scaffold was prepared leading to a prospective inhibitor for further development of a PDE2A PET imaging agent. BIT derivatives (BIT1-9) were obtained by a seven-step synthesis route, and their inhibitory potency towards PDE2A and selectivity over other PDEs were evaluated. BIT1 demonstrated much higher inhibition than other BIT derivatives (82.9% inhibition of PDE2A at 10 nM). BIT1 displayed an IC50 for PDE2A of 3.33 nM with 16-fold selectivity over PDE10A. This finding revealed that a derivative bearing both a 2-fluoro-pyridin-4-yl and 2-chloro-5-methoxy-phenyl unit at the 8- and 1-position, respectively, appeared to be the most potent inhibitor. In vitro studies of BIT1 using mouse liver microsomes (MLM) disclosed BIT1 as a suitable ligand for 18F-labeling. Nevertheless, future in vivo metabolism studies are required.


Assuntos
Encéfalo/enzimologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Compostos Radiofarmacêuticos/química , Triazinas/síntese química , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/química , Humanos , Ligantes , Camundongos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Triazinas/química , Triazinas/farmacologia
15.
Asian Pac J Cancer Prev ; 20(8): 2287-2297, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450897

RESUMO

Acute myeloid leukemia (AML) is symbolized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation, frequently resulting in hematopoietic insufficiency (granulocytopenia, thrombocytopenia, or anemia) with or without leukocytosis either by a predominance of immature forms or a loss of normal hematopoiesis. IDH2 gene encodes for isocitrate dehydrogenase enzyme which is involved in the TCA cycle domino effect and converts isocitrate to alpha-ketoglutarate. In the U.S, the annual incidence of AML progressively increases with age to a peak of 12.6 per 100,000 adults of 65 years or older. Mutations in isocitrate dehydrogenase 2 (arginine 132) have been demonstrated to be recurrent gene alterations in acute myeloid leukemia (AML) by forming 2-Hydroxy alpha ketoglutarate which, instead of participating in TCA cycle, accumulates to form AML. The current study approaches by molecular docking and virtual screening to elucidate inhibitor with superior affinity against IDH2 and achieve a pharmacological profile. To obtain the best established drug Molegro Virtual Docker algorithm was executed. The compound AG-221 (Pub CID 71299339) having the high affinity score was subjected to similarity search to retrieve the drugs with similar properties. The virtual screened compound SCHEMBL16391748 (PubChem CID-117816179) shows high affinity for the protein. Comparative study and ADMET study for both the above compounds resulted in equivalent chemical properties. Virtual screened compound SCHEMBL16391748 (PubChem CID-117816179) shows the lowest re-rank score. These drugs are identified as high potential IDH2 inhibitors and can halt AML when validated through further In vitro screening.


Assuntos
Ensaios de Triagem em Larga Escala , Isocitrato Desidrogenase/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Aminopiridinas/química , Aminopiridinas/metabolismo , Humanos , Isocitrato Desidrogenase/química , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Triazinas/química , Triazinas/metabolismo
16.
Chem Asian J ; 14(22): 3962-3968, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31389664

RESUMO

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3-deazaneplanocin A, galidesivir, GS-6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS-6620, remdesivir and pyrazofurin) are C-nucleosides, and two of them (GS-6620, remdesivir) also contain a phosphoramidate part. The C-nucleoside and phosphoramidate (and for the adenine analogues the 1'-cyano group as well) may be considered as essential attributes for their antiviral activity.


Assuntos
Adenina/análogos & derivados , Antivirais/química , Guanina/análogos & derivados , Febres Hemorrágicas Virais/tratamento farmacológico , Adenina/farmacologia , Adenina/uso terapêutico , Amidas/química , Amidas/metabolismo , Amidas/farmacologia , Amidas/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Pareamento de Bases , Ebolavirus/efeitos dos fármacos , Guanina/farmacologia , Guanina/uso terapêutico , Humanos , Nucleotídeos/química , Nucleotídeos/uso terapêutico , Ácidos Fosfóricos/química , Ácidos Fosfóricos/uso terapêutico , Pirazinas/química , Pirazinas/metabolismo , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Triazinas/química , Triazinas/uso terapêutico
17.
Arch Pharm (Weinheim) ; 352(9): e1900053, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31380598

RESUMO

The present research focused on designing a quinazoline skeleton, framed via 1,3,5-triazine derivatives (QBT) through field mapping and alignment studies. The QBT derivatives were synthesized via time- and cost-effective protocol. The 3D-QSAR study, computational physicochemical properties, and ADME calculation of the derivatives were performed to establish the affinity towards the biological system. Molecular docking in the adenosine triphosphate binding site of the RET tyrosine kinase domain (PDB ID: 7IVU) was studied to elucidate vital structural residues necessary for bioactivity. The derivatives were evaluated for anticancer potency against TPC-1 cells (thyroid cancer), MCF-7 cells (breast cancer), and one normal cell line (human foreskin fibroblasts) via 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay followed by an in ovo CAM assay. The entire series of derivatives (8a-o) showed mild to significant anticancer potency against the selected cancer cell lines.


Assuntos
Antineoplásicos/síntese química , Desenho de Drogas , Inibidores de Proteínas Quinases/síntese química , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Quinazolinas/química , Triazinas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Estrutura Molecular , Fosforilação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Relação Quantitativa Estrutura-Atividade , Triazinas/química , Triazinas/farmacologia
18.
Molecules ; 24(14)2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31337009

RESUMO

Organic room temperature persistent luminescence is a fascinating but still largely unexplored phenomenon. Cyclic-triimidazole and its halogenated (Br, I) derivatives have recently revealed as intriguing phosphors characterized by multifaceted emissive behavior including room temperature ultralong phosphorescence (RTUP) associated with the presence of H-aggregates in their crystal structure. Here, we move towards a multicomponent system by incorporating a fluoropyridinic fragment on the cyclic-triimidazole scaffold. Such chromophore enhances the molecular properties resulting in a high photoluminescence quantum yield (PL QY) in solution but preserves the solid-state RTUP. By means of X-ray diffraction (XRD) analysis, theoretical calculations, steady-state and time-resolved spectroscopy on solutions, polymethylmethacrylate (PMMA) blends and crystals, the nature of the different radiative deactivation channels of the compound has been disclosed. In particular, the molecular fluorescence and phosphorescence, this latter observed in frozen solution and in PMMA blends, are associated to deactivation from S1 and T1 respectively, while the low energy RTUP, observed only for crystals, is interpreted as originated from H aggregates.


Assuntos
Fluorescência , Luminescência , Temperatura Ambiente , Triazinas/química , Teoria da Densidade Funcional , Análise Espectral
19.
Molecules ; 24(14)2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295864

RESUMO

Extracellular acidification is an important feature of tumor microenvironments but has yet to be successfully exploited in cancer therapy. The reversal of the pH gradient across the plasma membrane in cells that regulate intracellular pH (pHi) has potential to drive the selective uptake of weak acids at low extracellular pH (pHe). Here, we investigate the dual targeting of low pHe and hypoxia, another key feature of tumor microenvironments. We prepared eight bioreductive prodrugs based on the benzotriazine di-oxide (BTO) nucleus by appending alkanoic or aminoalkanoic acid sidechains. The BTO acids showed modest selectivity for both low pHe (pH 6.5 versus 7.4, ratios 2 to 5-fold) and anoxia (ratios 2 to 8-fold) in SiHa and FaDu cell cultures. Related neutral BTOs were not selective for acidosis, but had greater cytotoxic potency and hypoxic selectivity than the BTO acids. Investigation of the uptake and metabolism of representative BTO acids confirmed enhanced uptake at low pHe, but lower intracellular concentrations than expected for passive diffusion. Further, the modulation of intracellular reductase activity and competition by the cell-excluded electron acceptor WST-1 suggests that the majority of metabolic reductions of BTO acids occur at the cell surface, compromising the engagement of the resulting free radicals with intracellular targets. Thus, the present study provides support for designing bioreductive prodrugs that exploit pH-dependent partitioning, suggesting, however, that that the approach should be applied to prodrugs with obligate intracellular activation.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Neoplasias/metabolismo , Pró-Fármacos , Triazinas/química , Triazinas/farmacologia , Linhagem Celular Tumoral , Fenômenos Químicos , Relação Dose-Resposta a Droga , Desenho de Drogas , Humanos , Modelos Biológicos , Estrutura Molecular , Oxirredução/efeitos dos fármacos , Óxidos
20.
Ecotoxicol Environ Saf ; 182: 109455, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31344592

RESUMO

Irgarol 1051 is highly toxic to marine autotrophs and has been widely used as an antifouling booster biocide. This study tested the toxicities of two s-triazine derivatives of Irgarol, namely M2 (3-[4-tert-butylamino-6-methylthiol-s-triazin-2-ylamino]propionaldehyde) and M3 (2-methylthio-4,6-bis-tert-butylamino-s-triazine) to two marine diatom species, Skeletonema costatum and Thalassiosira pseudonana through standard acute (96h) and chronic (7d) growth inhibition tests. Results showed that both of the two chemicals significantly inhibited the growth of S. costatum (M2: 96h-EC50 = 6789.7 µg L-1, 7d-EC50 = 3503.7 µg L-1; M3: 96h-EC50 = 45193.9 µg L-1, 7d-EC50 = 5330.0 µg L-1) and T. pseudonana (M2: 96h-EC50 = 366.2 µg L-1, 7d-EC50 = 312.5 µg L-1; M3: 96h-EC50 = 2633.4 µg L-1, 7d-EC50 = 710.5 µg L-1), while their toxicity effects were much milder than Irgarol and its major degradation product M1. By comparing with previous findings, the susceptibilities of these s-triazine compounds to two tested species were ranked as: Irgarol > M1 ≫ M2 > M3. This study promotes future research efforts on better understanding of the ecotoxicities of M2 and M3, and incorporating such information to improve the current monitoring, risk assessment and regulation of the use of Irgarol.


Assuntos
Diatomáceas/efeitos dos fármacos , Desinfetantes/toxicidade , Triazinas/toxicidade , Poluentes Químicos da Água/toxicidade , Diatomáceas/crescimento & desenvolvimento , Desinfetantes/química , Especificidade da Espécie , Relação Estrutura-Atividade , Testes de Toxicidade , Triazinas/química , Poluentes Químicos da Água/química
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