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1.
Food Chem ; 331: 127305, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32593038

RESUMO

An ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) method was established and validated for the simultaneous quantification of eight cyanogenic glucosides (CNGs) in agri-food. The eight CNGs were linamarin, lotaustralin, linustatin, neolinustatin, taxiphyllin, amygdalin, dhurrin and prunasin. CNGs were extracted with aqueous methanol and cleaned via solid-phase extraction. Analytes were separated with a C18 column via gradient elution. MS/MS analysis was performed with electrospray ionisation in positive mode. Quantification was performed in multiple reaction monitoring mode. Satisfactory validation results were obtained in terms of linearity, sensitivity, precision and accuracy, matrix effect and stability. The method was applied in typical cyanogenic agri-food. CNGs in cassava, linseed, bamboo, sorghum, apricot, almond and lima bean were analyzed.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Análise de Alimentos/métodos , Glucosídeos/análise , Glucosídeos/química , Nitrilos/química , Espectrometria de Massas em Tandem/métodos , Agricultura , Glucosídeos/isolamento & purificação , Extração em Fase Sólida , Fatores de Tempo
2.
Chemosphere ; 253: 126672, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464766

RESUMO

Mounting evidence highlights the negative impacts of neonicotinoids on non-target organisms and ecosystem, yet there are a few of methods to address the residual neonicotinoids in environment. Herein, series of sulfur and oxygen co-doped carbon nitride (SOCNx) were successfully synthesized via one-step thermal polymerization and applied in photodegradation of multi-neonicotinoids (dinotefuran, acetamiprid, clothianidin, thiacloprid, imidacloprid, nitenpyram and thiamethoxam) simultaneously for the first time. Unique tubular structure was observed at the specific doping ratio, which enhanced both mass transfer and specific surface area of graphitic carbon nitride (g-C3N4). The doping process changed the morphology of g-C3N4 materials and also affected its photocatalytic performance. The degradation rate of optimized material (SOCN8) for nitenpyram could surpass 90% just in 30 min under visible light in aqueous matrix. The degradation for target insecticide increased maximum efficiency of 57.6% compared to bulk g-C3N4. Moreover, the possible mechanism of the degradation process was proposed. The results revealed that photon-induced hole (h+) was the primary active species during the degradation of seven investigated neonicotinoids. Moreover, the SOCN8 showed excellent recyclability after four consecutive cycles, which implied promising applications for pesticide-contaminated water remedy.


Assuntos
Inseticidas/química , Neonicotinoides/química , Nitrilos/química , Fotólise , Catálise , Grafite/química , Inseticidas/efeitos da radiação , Neonicotinoides/efeitos da radiação , Compostos de Nitrogênio/química , Oxigênio/química , Enxofre/química
3.
PLoS One ; 15(5): e0230860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413033

RESUMO

Since 2000, human malaria cases in Malaysia were rapidly reduced with the use of insecticides in Indoor Residual Spray (IRS) and Long-Lasting Insecticide Net (LLIN). Unfortunately, monkey malaria in humans has shown an increase especially in Sabah and Sarawak. The insecticide currently used in IRS is deltamethrin K-Othrine® WG 250 wettable granule, targeting mosquitoes that rest and feed indoor. In Sabah, the primary vector for knowlesi malaria is An. balabacensis a species known to bite outdoor. This study evaluates an alternative method, the Outdoor Residual Spray (ORS) using a novel formulation of deltamethrin K-Othrine® (PolyZone) to examine it suitability to control knowlesi malaria vector in Sabah, compared to the current method. The study was performed at seven villages in Sabah having similar type of houses (wood, bamboo and concrete). Houses were sprayed with deltamethrin K-Othrine® (PolyZone) at two different dosages, 25 mg/m2 and 30 mg/m2 and deltamethrin K-Othrine® WG 250 wettable granule at 25 mg/m2, sprayed indoor and outdoor. Residual activity on different walls was assessed using standard cone bioassay techniques. For larval surveillances, potential breeding sites were surveyed. Larvae were collected and identified, pre and post spraying. Adult survey was done using Human Landing Catch (HLC) performed outdoor and indoor. Detection of malaria parasite in adults was conducted via microscopy and molecular methods. Deltamethrin K-Othrine® (PolyZone) showed higher efficacy when sprayed outdoor. The efficacy was found varied when sprayed on different types of wall surfaces. Deltamethrin K-Othrine® (PolyZone) at 25 mg/m2 was the most effective with regards to ability to high mortality and effective knock down (KD). The vector population was reduced significantly post-spraying and reduction in breeding sites as well. The number of simian malaria infected vector, human and simian malaria transmission were also greatly reduced.


Assuntos
Anopheles/efeitos dos fármacos , Inseticidas/toxicidade , Malária/prevenção & controle , Doenças Parasitárias em Animais/prevenção & controle , Aerossóis , Animais , Anopheles/parasitologia , Haplorrinos , Inseticidas/química , Malária/transmissão , Malásia , Nitrilos/química , Doenças Parasitárias em Animais/transmissão , Plasmodium knowlesi/patogenicidade , Piretrinas/química
4.
AAPS PharmSciTech ; 21(3): 111, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236750

RESUMO

Low solubility of active pharmaceutical compounds (APIs) remains an important challenge in dosage form development process. In the manuscript, empirical models were developed and analyzed in order to predict dissolution of bicalutamide (BCL) from solid dispersion with various carriers. BCL was chosen as an example of a poor water-soluble API. Two separate datasets were created: one from literature data and another based on in-house experimental data. Computational experiments were conducted using artificial intelligence tools based on machine learning (AI/ML) with a plethora of techniques including artificial neural networks, decision trees, rule-based systems, and evolutionary computations. The latter resulting in classical mathematical equations provided models characterized by the lowest prediction error. In-house data turned out to be more homogeneous, as well as formulations were more extensively characterized than literature-based data. Thus, in-house data resulted in better models than literature-based data set. Among the other covariates, the best model uses for prediction of BCL dissolution profile the transmittance from IR spectrum at 1260 cm-1 wavenumber. Ab initio modeling-based in silico simulations were conducted to reveal potential BCL-excipients interaction. All crucial variables were selected automatically by AI/ML tools and resulted in reasonably simple and yet predictive models suitable for application in Quality by Design (QbD) approaches. Presented data-driven model development using AI/ML could be useful in various problems in the field of pharmaceutical technology, resulting in both predictive and investigational tools revealing new knowledge.


Assuntos
Anilidas/química , Inteligência Artificial , Aprendizado de Máquina , Nitrilos/química , Compostos de Tosil/química , Pós , Solubilidade , Tecnologia Farmacêutica
5.
Nat Chem Biol ; 16(5): 497-506, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32231343

RESUMO

We recently described glutathione peroxidase 4 (GPX4) as a promising target for killing therapy-resistant cancer cells via ferroptosis. The onset of therapy resistance by multiple types of treatment results in a stable cell state marked by high levels of polyunsaturated lipids and an acquired dependency on GPX4. Unfortunately, all existing inhibitors of GPX4 act covalently via a reactive alkyl chloride moiety that confers poor selectivity and pharmacokinetic properties. Here, we report our discovery that masked nitrile-oxide electrophiles, which have not been explored previously as covalent cellular probes, undergo remarkable chemical transformations in cells and provide an effective strategy for selective targeting of GPX4. The new GPX4-inhibiting compounds we describe exhibit unexpected proteome-wide selectivity and, in some instances, vastly improved physiochemical and pharmacokinetic properties compared to existing chloroacetamide-based GPX4 inhibitors. These features make them superior tool compounds for biological interrogation of ferroptosis and constitute starting points for development of improved inhibitors of GPX4.


Assuntos
Inibidores Enzimáticos/farmacologia , Nitrilos/química , Nitrilos/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Animais , Linhagem Celular Tumoral , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Ferroptose/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos SCID , Sondas Moleculares/química , Terapia de Alvo Molecular , Óxidos/química , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/química , Pró-Fármacos/química , Ratos Wistar , Selenocisteína/química , Selenocisteína/metabolismo , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-Atividade
6.
PLoS One ; 15(4): e0231251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287300

RESUMO

Outdoor residual spraying is proposed for the control of exophilic mosquitoes. However, the residual effect of insecticide mists applied to outdoor resting habitats of mosquitoes is not well characterized. The objective of this study was to assess the longevity of the residual insecticidal effect of three pyrethroid formulations applied to outdoor vegetation against the Southeast Asian malaria vector Anopheles dirus. Lambda-cyhalothrin capsule suspension, deltamethrin emulsifiable concentrate and bifenthrin wettable powder were sprayed on dense bamboo bushes on the Thailand-Myanmar border during the dry season 2018. The duration and magnitude of the residual insecticidal effect were assessed weekly with a standard cone assay, using freshly collected insecticide-treated bamboo leaves and a laboratory-adapted colony of Anopheles dirus sensu stricto susceptible to pyrethroids. The experiment was repeated during the rainy season to assess the persistence of the lambda-cyhalothrin formulation after natural rains and artificial washings. During the dry season (cumulative rainfall = 28 mm in 111 days), mortality and knockdown (KD) rates were >80% for 60 days with bifenthrin and 90 days with lambda-cyhalothrin and deltamethrin. The 50% knockdown time (TKD50) was <15 min with lambda-cyhalothrin and deltamethrin, and <30 min with bifenthrin. During the rainy season (cumulative rainfall = 465 mm in 51 days), mortality and KD rates were >80% for 42 days and TKD50 was <15 min with lambda-cyhalothrin. Additional artificial washing of the testing material with 10L of tap water before performing the cone tests had no significant effect on the residual insecticidal effect of this formulation. Long-lasting residual insecticidal effect can be obtained when spraying pyrethroid insecticides on the outdoor resting habitats of malaria vectors.


Assuntos
Anopheles/efeitos dos fármacos , Insetos Vetores/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Nitrilos/farmacologia , Piretrinas/farmacologia , Animais , Anopheles/crescimento & desenvolvimento , Insetos Vetores/crescimento & desenvolvimento , Inseticidas/química , Mianmar , Nitrilos/química , Piretrinas/química , Tailândia
7.
Mar Biotechnol (NY) ; 22(2): 317-330, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124098

RESUMO

The organic synthesis has been driven by the need of sustainable processes, which also requires efficiency and cost-effectiveness. In this work, we described the synthesis of nine Knoevenagel adducts between cyanoacetamide and aromatic aldehydes ((E)-2-cyano-3-(phenyl)acrylamide derivatives), employing triethylamine as catalyst under microwave irradiation in 30 min with excellent yields (93-99% yield). Then, these adducts were employed in the C-C double bond bioreduction by the marine-derived fungus Cladosporium sp. CBMAI 1237 for obtention of 2-cyano-3-phenylpropanamide derivatives in mild conditions and short reaction time for a whole-cells reduction (phosphate buffer pH 7.0, 32 °C, 130 rpm, 8 h) with good yields (48-90%). It is important to emphasize that the experimental conditions, especially the reaction time, should be carefully evaluated for the obtention of high yields. Since a biodegradation process consumed the obtained product in extended periods, probably due to the use of the substrate as carbon and nitrogen source. This approach showed that the use of coupled and greener catalysis methods such as microwave irradiation and biocatalytic reduction, which employs unique biocatalysts like marine-derived fungi, can be an interesting tool for the obtention of organic molecules.


Assuntos
Amidas/síntese química , Biocatálise , Cladosporium/metabolismo , Micro-Ondas , Aldeídos/química , Etilaminas/química , Nitrilos/química
8.
J Chromatogr A ; 1620: 461007, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32151417

RESUMO

Evaluation of chiral pesticides remains a frequently neglected matter in routine food control laboratories. This fact is due to the existence of many residue definitions but also due to the lack of robust instrumental methods for the evaluation of these isomeric compounds. However, supercritical fluid chromatography coupled to mass spectrometry (SFC-ESI-MS/MS) has been demonstrated to perform fast and highly efficient separations without the need to change the mobile phase employed in multiresidue pesticide analyses. Regarding chiral stationary phase columns, the polysaccharide-based ones clearly demonstrate the best separation technology. Two polysaccharide-based columns were tested in this study, and the robustness of their combination with SFC was verified. The enantiomers of lambda-cyhalothrin and metalaxyl were studied precisely due to their markedly distinct toxicity and enantioselectivity. Furthermore, the acute reference dose for gamma-cyhalothrin is half in comparison with its enantiomer (0.0025 and 0.005 mg/kg respectively), which is present in the lambda-cyhalothin residue definition. These enantiomers were analyzed in terms of linearity, reproducibility, and matrix effects in four representative matrices (tomato, orange, leek, and cayenne). Additionally, field tests under greenhouse conditions for these compounds were performed. The results obtained after different sample collections revealed a similar degradation in lambda-cyhalothrin enantiomers (R, S, S, and S, R, R) but not in the case of metalaxyl-M (mefenoxam) where the degradation in tomato was 2 to 6 times less in comparison with its S-enantiomer.


Assuntos
Alanina/análogos & derivados , Cromatografia com Fluido Supercrítico/métodos , Nitrilos/análise , Praguicidas/análise , Piretrinas/análise , Alanina/análise , Alanina/química , Nitrilos/química , Praguicidas/química , Polissacarídeos/química , Piretrinas/química , Reprodutibilidade dos Testes , Estereoisomerismo , Espectrometria de Massas em Tandem
9.
Org Biomol Chem ; 18(7): 1279-1336, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32025682

RESUMO

Enantio- and diastereodivergent routes to marine-origin natural products with different sizes of cyclic ethers and lactones have been used in order to assign stereochemical features. Kainoid amino acids such as isodomoic acids have been synthesized using diastereodivergent routes. The bis(indole) alkaloid dragmacidin F has been prepared by enantiodivergent strategies as well as furanoterpenes and the tetracyclic agelastatin A. Natural products containing five-membered lactones like quercus lactones, muricatacins, goniofufuranones, methylenolactocins and frenolicin B have been synthesized using stereodivergent routes. Macrolides are very abundant lactones and have been mainly prepared from the corresponding seco-acids by lactonization, such as lasiodiplodin, zaeralanes, macrosphelides and haloprins, or by ring-closing metathesis, such as aspercyclides, microcarpalides, macrolides FD-891 and 892, and tetradic-5-en-9-olides. Other natural products including cyclic ethers (such as sesamin, asarinin, acetogenins, centrolobines and nabilones), alcohols (such as sulcatol), esters (such as methyl jasmonates), polycyclic precursors of fredericamycin, amino alcohols (such as ambroxol and sphingosines), isoprostanes, isofurans, polyketide precursors of anachelins, brevicomins, gummiferol, shikimic acid and the related compounds, and the pheromone disparlure have been synthesized stereodivergently. Heterocyclic systems such as epoxides, theobroxides and bromoxones, oxetan-3-ones, 5- to 8-membered cyclic ethers, azetidones, γ-lactams, oxazolidinones, bis(oxazolines), dihydropyridoisoindolines and octahydroisoquinolines have been prepared following stereodivergent routes. Stereodivergent routes to unnatural compounds such as alkenes, dienes, allenes, cyclopropanes, alcohols, aldols, amines, amino alcohols, ß-amino acids, carboxylic acids, lactones, nitriles and α-amino nitriles have been considered as well.


Assuntos
Produtos Biológicos/síntese química , Compostos Heterocíclicos/síntese química , Lactonas/síntese química , Álcoois/síntese química , Álcoois/química , Alcenos/síntese química , Alcenos/química , Aminas/síntese química , Aminas/química , Aminoácidos/síntese química , Aminoácidos/química , Produtos Biológicos/química , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Compostos Heterocíclicos/química , Lactonas/química , Estrutura Molecular , Nitrilos/síntese química , Nitrilos/química , Estereoisomerismo
10.
Molecules ; 25(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936309

RESUMO

A series of novel 7-substituted-5-(1H-indol-3-yl)tetrazolo[1,5-a]pyrimidine-6-carbonitrile was synthesized via a one-pot, three-multicomponent reaction of appropriate aldehydes, 1H-tetrazole-5-amine and 3-cyanoacetyl indole in catalytic triethylamine. The cytotoxic activity of the new synthesized tetrazolopyrimidine-6-carbonitrile compounds was investigated against HCT-116, MCF-7, MDA-MB-231, A549 human cancer cell lines and one human healthy normal cell line (RPE-1) using the MTT cytotoxicity assay. Compounds 4h, 4b, 4c, 4i and 4a showed potent anticancer activities against human colon cancer. Additionally, all the compounds showed potent anticancer activities on human lung cancer.


Assuntos
Nitrilos/farmacologia , Pirimidinas/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Concentração Inibidora 50 , Nitrilos/síntese química , Nitrilos/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
11.
Molecules ; 25(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941051

RESUMO

A high-nitrogen compound, 2,2'-azobis(1H-imidazole-4,5-dicarbonitrile) (TCAD), was synthesized from commercially available 2-amino-1H-imidazole-4,5-dicarbonitrile. It was characterized with infrared and nuclear magnetic resonance spectroscopy. Its structure was determined by single crystal X-ray diffraction. The crystal of TCAD tetrahydrate is monoclinic, with space group P21/c with crystal parameters of a = 10.2935(2) Å, b = 7.36760(10) Å, c = 20.1447(4) Å, V = 1500.27(5) Å3, Z = 4, and F(000) = 688. Computational methods were used in order to fully optimize the molecular structure, calculate the electrostatic potential of an isolated molecule, and to compute thermodynamic parameters. TCAD has very high thermal stability with temperature of decomposition at 369 °C. Kinetics of thermal decomposition of this compound were studied and apparent energy of activation as well as the maximum safe temperature of technological process were determined.


Assuntos
Imidazóis/química , Nitrilos/química , Cinética , Modelos Moleculares , Estrutura Molecular , Difração de Raios X
12.
Molecules ; 25(2)2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31940892

RESUMO

Understanding the solvation and ion-pairing interactions of anionic substrates in room-temperature ionic liquids (RTIL) is key for the electrochemical applications of these new classes of solvents. In this work, cyclic voltammetry and visible and infrared spectroelectrochemistry of tetracyanoquinodimethane (TCNQ) was examined in molecular (acetonitrile) and RTIL solvents, as well as mixtures of these solvents. The overall results were consistent with the formation of RTIL/acetonitrile nanodomains. The voltammetry indicated that the first electrogenerated product, TCNQ-, was not incorporated into the RTIL nanodomain, while the second electrogenerated product, TCNQ2-, was strongly attracted to the RTIL nanodomain. The visible spectroelectrochemistry was also consistent with these observations. Infrared spectroelectrochemistry showed no discrete ion pairing between the cation and TCNQ- in either the acetonitrile or RTIL solutions. Discrete ion pairing was, however, observed in the acetonitrile domain between the tetrabutylammonium ion and TCNQ2-. On the other hand, no discrete ion pairing was observed in BMImPF6 or BMImBF4 solutions with TCNQ2-. In BMImNTf2, however, discrete ion pairs were formed with BMIm+ and TCNQ2-. Density function theory (DFT) calculations showed that the cations paired above and below the aromatic ring. The results of this work support the understanding of the redox chemistry in RTIL solutions.


Assuntos
Acetonitrilos/química , Líquidos Iônicos/química , Nitrilos/química , Solventes/química , Técnicas Eletroquímicas , Modelos Químicos , Oxirredução , Teoria Quântica , Soluções , Termodinâmica
14.
J Agric Food Chem ; 68(5): 1397-1404, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31917559

RESUMO

Volatiles affect tea (Camellia sinensis) aroma quality and have roles in tea plant defense against stresses. Some volatiles defend against stresses through their toxicity, which might affect tea safety. Benzyl nitrile is a defense-related toxic volatile compound that accumulates in tea under stresses, but its formation mechanism in tea remains unknown. In this study, l-[2H8]phenylalanine feeding experiments and enzyme reactions showed that benzyl nitrile was generated from l-phenylalanine via phenylacetaldoxime in tea. CsCYP79D73 showed activity for converting l-phenylalanine into phenylacetaldoxime, while CsCYP71AT96s showed activity for converting phenylacetaldoxime into benzyl nitrile. Continuous wounding in the oolong tea process significantly enhanced the CsCYP79D73 expression level and phenylacetaldoxime and benzyl nitrile contents. Benzyl nitrile accumulation under continuous wounding stress was attributed to an increase in jasmonic acid, which activated CsCYP79D73 expression. This represents the first elucidation of the formation mechanism of benzyl nitrile in tea.


Assuntos
Camellia sinensis/metabolismo , Nitrilos/metabolismo , Fenilalanina/metabolismo , Camellia sinensis/química , Camellia sinensis/genética , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Ciclopentanos/metabolismo , Nitrilos/química , Oxilipinas/metabolismo , Fenilalanina/química , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico
15.
J Agric Food Chem ; 68(3): 735-741, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31895559

RESUMO

Facile fabrication of difunctional nanoparticles (NPs) for pesticide delivery and imaging is still a fascinating challenge. Here, water-dispersible difunctional NPs were developed using flash nanoprecipitation (FNP) where self-assembling amphiphilic block copolymers were used to encapsulate a highly hydrophobic model pesticide, Lambda-cyhalothrin, and the fluorescent dye Nile red. The particle size (ranging from 158 to 280 nm) and fluorescence property of NPs could be controlled by varying the flow rate or Nile red feed concentration. The aggregation state and rearrangement of the dye molecules in the NPs were also investigated. IVIS imaging and confocal laser scanning microscopy analysis demonstrated that the resulting difunctional nanopesticide particles could allow accurate in situ tracking of the pesticide on the leaf surface, while effectively avoiding interference from chlorophyll autofluorescence. The difunctional NP suspension maintained high insecticidal activity and stability. This work demonstrates the feasibility and great potential of the FNP method in universal fabrication of multifunctional NPs with in situ pesticide tracing and crop protection capabilities.


Assuntos
Nanopartículas/química , Nitrilos/química , Imagem Óptica/métodos , Praguicidas/química , Piretrinas/química , Proteção de Cultivos , Fluorescência , Tamanho da Partícula , Folhas de Planta/química , Polietilenoglicóis/química
16.
Chem Pharm Bull (Tokyo) ; 68(1): 1-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902899

RESUMO

Novel reactions using hetero-heavy atoms (P, S, Si, Se, and Sn) were developed and applied to the synthesis of biofunctional molecules and some medicine-candidates, in which the following items are covered. 1) Development of introduction of C1-unit using cyanophosphates (CPs). 2) Carbene-generation under neutral condition from CPs and its application to organic synthesis. 3) [3,3]Sigmatropic rearrangement-ring expansion reactions of medium-sized cyclic thionocarbonates containing a sulfur atom and their application to natural product synthesis. 4) Stereoselective synthesis of novel ß-imidazole C-nucleosides via diazafulvene intermediates and their application to investigating ribozyme reaction mechanism. 5) Developments of novel histamine H3- and H4-receptor ligands using new synthetic methods involving Se or Sn atoms.


Assuntos
Produtos Biológicos/química , Metais/química , Animais , Produtos Biológicos/síntese química , Proliferação de Células/efeitos dos fármacos , Agonistas dos Receptores Histamínicos/síntese química , Agonistas dos Receptores Histamínicos/química , Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/síntese química , Antagonistas dos Receptores Histamínicos/química , Antagonistas dos Receptores Histamínicos/farmacologia , Humanos , Metano/análogos & derivados , Metano/química , Metano/metabolismo , Nitrilos/química , Nucleosídeos/síntese química , Nucleosídeos/química
17.
Pharm Res ; 37(3): 36, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965346

RESUMO

PURPOSE: We describe the preparation of injectable polymeric paste (IPP) formulations for local and sustained release of drugs. Furthermore, we include the characterization and possible applications of such pastes. Particular attention is paid to characteristics relevant to the successful clinical formulation development, such as viscosity, injectability, degradation, drug release, sterilization, stability performance and pharmacokinetics. METHODS: Paste injectability was characterized using measured viscosity and the Hagen-Poiseuille equation to determine injection forces. Drug degradation, release and formulation stability experiments were performed in vitro and drug levels were quantified using HPLC-UV methods. Pharmacokinetic evaluation of sustained-release lidocaine IPPs used five groups of six rats receiving increasing doses subcutaneously. An anti-cancer formulation was evaluated in a subcutaneous tumor xenograft mouse model. RESULTS: The viscosity and injectability of IPPs could be controlled by changing the polymeric composition. IPPs demonstrated good long-term stability and tunable drug-release with low systemic exposure in vivo in rats. Preliminary data in a subcutaneous tumor model points to a sustained anticancer effect. CONCLUSIONS: These IPPs are tunable platforms for local and sustained delivery of drugs and have potential for further clinical development to treat a number of diseases.


Assuntos
Portadores de Fármacos/química , Composição de Medicamentos/métodos , Pomadas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Anilidas/química , Anilidas/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Docetaxel/química , Docetaxel/farmacologia , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Injeções , Lidocaína/química , Lidocaína/farmacocinética , Masculino , Camundongos , Camundongos Nus , Neoplasias Experimentais , Nitrilos/química , Nitrilos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Ratos , Compostos de Tosil/química , Compostos de Tosil/farmacologia , Viscosidade
18.
J Agric Food Chem ; 68(6): 1546-1554, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31986047

RESUMO

Bromoxynil is an increasingly applied nitrile herbicide. Under aerobic conditions, hydration, nitrilation, or hydroxylation of the nitrile group commonly occurs, whereas under anaerobic conditions reductive dehalogenation is common. This work studied the isotope effects associated with these processes by soil cultures. The aerobic soil enrichment culture presented a significant increase in Stenotrophomonas, Pseudomonas, Chryseobacterium, Achromobacter, Azospirillum, and Arcticibacter, and degradation products indicated that nitrile hydratase was the dominant degradation route. The anaerobic culture was dominated by Proteobacteria and Firmicutes phyla with a significant increase in Dethiosulfatibacter, and degradation products indicated reductive debromination as a major degradation route. Distinct dual-isotope trends (δ13C, δ15N) were determined for the two routes: a strong inverse nitrogen isotope effect (εN = 10.56 ± 0.36‰) and an insignificant carbon isotope effect (εC = 0.37 ± 0.36‰) for the aerobic process versus a negligible effect for both elements in the anaerobic process. These trends differ from formerly reported trends for the photodegradation of bromoxynil and enable one to distinguish between the processes in the field.


Assuntos
Bactérias/metabolismo , Herbicidas/química , Nitrilos/química , Poluentes do Solo/química , Aerobiose , Anaerobiose , Biodegradação Ambiental , Isótopos de Carbono/química , Isótopos de Nitrogênio/química , Solo/química , Microbiologia do Solo
19.
Talanta ; 209: 120579, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892066

RESUMO

Sialic acid (SA) is a special monosaccharide widely distributed at the termini of sugar chains on the cell surface, and its expression level is closely connected with various biological and pathological processes. Therefore, accurate quantitative detection of SA on cancer cell surface is of great significance for clinical diagnosis and therapy. Here, we developed a whole-surface accessible method of accurate SERS quantification of SA level on a single cell, in which silver nanoparticles functionalized with 4-mercaptophenylboric acid and 4-mercaptobenzenitrile was used as the background-free SERS probe. The cyano group on the nanoprobe showed a unique Raman shift at 2232 cm-1, where most of the biological samples have no Raman response. Meanwhile, the boronic acid group had high specificity to SA molecules at physiological pH. The expression level of SA can be accurately quantitated on the basis of the CN Raman signal. The average number of expressed SA molecules on the surface of a single HeLa cell was 4.6 × 107. And SERS imaging of a single cell was achieved at 2232 cm-1 without biological interference. We evaluated SA expression level on the surface of different cancer cells and dynamically monitored SA expression under the influence of drugs. The proposed approach is accurate as well as sensitive for background-free quantification of SA on cell surface, which is promising for revealing the relationship between tumors and cell surface glycosylation.


Assuntos
Nanopartículas Metálicas/química , Ácidos Siálicos/análise , Prata/química , Análise Espectral Raman/métodos , Compostos de Sulfidrila/química , Ácidos Bóricos/química , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Nitrilos/química , Análise de Célula Única/métodos
20.
Phytochemistry ; 170: 112214, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31794881

RESUMO

In recent years, ionic liquids and deep eutectic solvents (DESs) have gained increasing attention due to their ability to extract and solubilize metabolites and biopolymers in quantities far beyond their solubility in oil and water. The hypothesis that naturally occurring metabolites are able to form a natural deep eutectic solvent (NADES), thereby constituting a third intracellular phase in addition to the aqueous and lipid phases, has prompted researchers to study the role of NADES in living systems. As an excellent solvent for specialized metabolites, formation of NADES in response to dehydration of plant cells could provide an appropriate environment for the functional storage of enzymes during drought. Using the enzymes catalyzing the biosynthesis of the defense compound dhurrin as an experimental model system, we demonstrate that enzymes involved in this pathway exhibit increased stability in NADES compared with aqueous buffer solutions, and that enzyme activity is restored upon rehydration. Inspired by nature, application of NADES provides a biotechnological approach for long-term storage of entire biosynthetic pathways including membrane-anchored enzymes.


Assuntos
Produtos Biológicos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Nitrilos/metabolismo , Compostos Fitoquímicos/biossíntese , Sorghum/química , Produtos Biológicos/química , Estrutura Molecular , Nitrilos/química , Compostos Fitoquímicos/química , Solubilidade , Solventes , Sorghum/citologia , Sorghum/metabolismo
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