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1.
Molecules ; 28(13)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37446804

RESUMEN

The present study was conducted to analyze the level of four priority polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), chrysene (Chr), benzo[a]anthracene (BaA), and benzo[b]fluoranthene (BbF), in traditionally smoked chicken products marketed in China. The results show that the amount of Æ©PAH4 (the sum of four different PAHs: BaP, Chr, BaA, and BbF) was 30.43-225.17 and 18.75-129.54 µg/kg in the skin and meat of smoked chicken products, respectively. The content of Æ©PAH4 in the smoked skin was significantly higher as compared to the smoked meat (p < 0.05). The calculation of MOE (margin of exposure) results suggested the possibilities of ingestion risk associated with the consumption of smoked chicken skin. Furthermore, the formaldehyde content in the skin of smoked chicken was 2.17-6.84 mg/kg and 0.86-2.95 mg/kg in the smoked meat. These results indicate that optimization or alternative methods for food processing should be developed to reduce the high level of harmful substances formed during processing to ensure the safety of smoked chicken products. Moreover, along with harmful substances, the moisture content and color of traditionally smoked chicken were analyzed to provide a practical reference for healthy, safe and green processing technology for smoked chicken.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Animales , Hidrocarburos Policíclicos Aromáticos/análisis , Humo , Pollos , Crisenos
2.
Molecules ; 28(1)2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36615617

RESUMEN

Soil organic matter (SOM) and its heterogeneous nature constitutes the main factor determining the fate and transformation of organic chemicals (OCs). Thus, the aim of thus research was to analyze the influence of the molecular chemodiversity of a stable SOM (S-SOM) on the sorption potential of different groups of OCs (organochloride pesticides­OCPs, and non-chlorinated pesticides­NCPs, polycyclic aromatic hydrocarbons­PAHs). The research was conducted as a batch experiment. For this purpose, a S-SOM was separated from six soils (TOC = 15.0−58.7 gkg−1; TN = 1.4−6.6 gkg−1, pH in KCl = 6.4−7.4 and WRB taxonomy: fluvisols, luviosols, leptosols) by alkaline urea and dimethylsulphoxide with sulfuric acid. Isolated S-SOM fraction was evaluated by UV−VIS, FT-IR and EEM spectroscopy to describe molecular diversity, which allowed the assessment of its potential sorption properties regarding OCs. In order to directly evaluate the sorption affinity of individual OCs to S-SOM, the mixture of the 3 deuterated contaminants: chrysene (PAHs), 4,4'DDT (OCPs) atrazine (NCPs) were applied. The sorption experiment was carried out according to the 106 OECD Guidelines. The OCs concentration was analyzed by gas chromatography triple mass spectrometry (GC-MS/MS). OCs were characterized by different sorption rates to S-SOM fractions according to the overall trend: atrazine (87.5−99.9%) > 4,4'DDT (64−81.6%) > chrysene (35.2−79.8%). Moreover, atrazine exhibited the highest saturation dynamic with fast bounding time amounting to 6 h of contact with S-SOM. Proportionally, the chrysene showed the slowest binding time achieving an average of 55% sorption after 78 h. Therefore, S-SOM isolated from different soils demonstrated varying binding capacity to OCs (CoV = 21%, 27% and 33% for atrazine, DDT and chrysene, respectively). Results indicate that each sample contains S-SOM with different degrees of transformation and sorption properties that affect the OCs availability in soil. Spectroscopic analyses have shown that the main component of S-SOM are biopolymers at various stages of transformation that contain numerous aromatic−aliphatic groups with mostly hydrophilic substituents.


Asunto(s)
Atrazina , Plaguicidas , Contaminantes del Suelo , Suelo/química , Atrazina/química , Crisenos , Espectroscopía Infrarroja por Transformada de Fourier , DDT , Espectrometría de Masas en Tándem , Adsorción , Plaguicidas/análisis , Compuestos Orgánicos/química , Contaminantes del Suelo/análisis
3.
J Environ Sci (China) ; 124: 782-793, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36182183

RESUMEN

Nitrated polycyclic aromatic hydrocarbons (NPAHs) are widespread organic pollutants that possess carcinogenic and mutagenic properties, so they may pose a risk to the environment and human health. In this study, the concentrations of 15 NPAHs and 16 polycyclic aromatic hydrocarbons (PAHs) in 30 surface water samples and 26 sediment samples were measured in 2018 from the Taige Canal, one of the main rivers flowing into Taihu Lake, China. The total NPAH concentrations in water and sediment ranged from 14.7 to 235 ng/L and 22.9 to 96.5 ng/g dw, respectively. 9-nitrophenanthrene (nd-76.3 ng/L) was the dominant compound in surface water, while 2+3-nitrofluoranthene (1.73-18.1 ng/g dw) dominated in sediment. Among PAHs, concentration ranging from 1,097 to 2,981 ng/L and 1,089 to 4,489 ng/g dw in surface water and sediment, respectively. There was a strong positive correlation between the log octanol-water partition coefficient (Kow) and log sediment-water partition coefficient due to hydrophobic interaction. The fugacity fraction value increased with the decrease of log Kow, and chrysene was transferred from water into sediment. The residual NPAHs in surface water and sediment of the Taige Canal have partial correlation. Diesel engine and coal combustion emissions were probably the principal sources of NPAHs in surface water and sediment. The results of ecological risk assessment showed that some NPAHs in water (e.g, 1-nitropyrene and 6-nitrochrysene) and sediment (e.g., 2-nitrobiphenyl, 5-nitroacenaphthene, 9-nitrophenanthrene and 2+3-nitrofluoranthene) had moderate ecological risks, which should be of concern.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , China , Crisenos/análisis , Carbón Mineral/análisis , Monitoreo del Ambiente/métodos , Fluorenos , Sedimentos Geológicos/química , Humanos , Nitratos , Octanoles , Fenantrenos , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo , Agua , Contaminantes Químicos del Agua/análisis
4.
Carcinogenesis ; 43(8): 746-753, 2022 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-35749296

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are recognized as potential etiological agents in the development of oral cancer in smokers. In particular, benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DB[a,l]P) are detected in cigarette smoke and the environment and can induce DNA damage, mutagenesis and carcinogenesis in the oral cavity of rodents. Consequently, DNA adducts are regarded as the most direct markers of genotoxicity and can be used as biomarkers of cancer risk. Thus, this study used LC-MS/MS analysis with isotope labeled internal standard to detect and quantify DNA adducts derived from B[a]P and DB[a,l]P in buccal cells of cigarette smokers and non-smokers. Participants in this study include 21 smokers and 16 non-smokers. Our data are the first to report that levels (mean ± SD) of BPDE-N2-dG were significantly (P < 0.001) higher in smokers (20.18 ± 8.40 adducts/108 dG) than in non-smokers (0.84 ± 1.02 adducts/108 dG). Likewise, levels of DBPDE-N6-dA in smokers (5.49 ± 3.41 adducts/108 dA) were significantly higher (P = 0.019) than non-smokers (2.76 ± 2.29 adducts/108 dA). Collectively, the results of this clinical study support that PAHs in tobacco smoke can contribute to the development of oral cancer in humans.


Asunto(s)
Neoplasias de la Boca , Hidrocarburos Policíclicos Aromáticos , Productos de Tabaco , Contaminación por Humo de Tabaco , Benzo(a)pireno/toxicidad , Carcinógenos/análisis , Carcinógenos/toxicidad , Cromatografía Liquida , Crisenos/análisis , Aductos de ADN , Humanos , Mucosa Bucal , Neoplasias de la Boca/inducido químicamente , Neoplasias de la Boca/genética , Hidrocarburos Policíclicos Aromáticos/toxicidad , Espectrometría de Masas en Tándem , Nicotiana/efectos adversos , Productos de Tabaco/toxicidad
5.
Toxicol Appl Pharmacol ; 438: 115830, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34933053

RESUMEN

Dibenzo[def,p]chrysene (DBC) is an environmental polycyclic aromatic hydrocarbon (PAH) that causes tumors in mice and has been classified as a probable human carcinogen by the International Agency for Research on Cancer. Animal toxicity studies often utilize higher doses than are found in relevant human exposures. Additionally, like many PAHs, DBC requires metabolic bioactivation to form the ultimate toxicant, and species differences in DBC and DBC metabolite metabolism have been observed. To understand the implications of dose and species differences, a physiologically based pharmacokinetic model (PBPK) for DBC and major metabolites was developed in mice and humans. Metabolism parameters used in the model were obtained from experimental in vitro metabolism assays using mice and human hepatic microsomes. PBPK model simulations were evaluated against mice dosed with 15 mg/kg DBC by oral gavage and human volunteers orally microdosed with 29 ng of DBC. DBC and its primary metabolite DBC-11,12-diol were measured in blood of mice and humans, while in urine, the majority of DBC metabolites were obeserved as conjugated DBC-11,12-diol, conjugated DBC tetrols, and unconjugated DBC tetrols. The PBPK model was able to predict the time course concentrations of DBC, DBC-11,12-diol, and other DBC metabolites in blood and urine of human volunteers and mice with reasonable accuracy. Agreement between model simulations and measured pharmacokinetic data in mice and human studies demonstrate the success and versatility of our model for interspecies extrapolation and applicability for different doses. Furthermore, our simulations show that internal dose metrics used for risk assessment do not necessarily scale allometrically, and that PBPK modeling provides a reliable approach to appropriately account for interspecies differences in metabolism and physiology.


Asunto(s)
Crisenos/administración & dosificación , Crisenos/farmacocinética , Cistina/análogos & derivados , Animales , Carcinógenos/administración & dosificación , Carcinógenos/farmacocinética , Cistina/administración & dosificación , Cistina/farmacocinética , Femenino , Humanos , Masculino , Ratones , Modelos Biológicos , Neoplasias/inducido químicamente
6.
Chem Res Toxicol ; 35(11): 2152-2159, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36260657

RESUMEN

In a series of previous studies we reported that black raspberry (BRB) powder inhibits dibenzo[a,l]pyrene (DBP)-induced DNA damage, mutagenesis, and oral squamous cell carcinoma (OSCC) development in mice. In the present study, using human oral leukoplakia (MSK-Leuk1) and squamous cell carcinoma (SCC1483) cells, we tested the hypothesis that BRB extract (BRBE) will enhance the synthesis of glutathione (GSH) and in turn increase GSH conjugation of the fjord-region DBP diol epoxide (DBPDE) derived from DBP leading to inhibition of DBP-induced DNA damage. The syntheses of DBPDE-GSH conjugate, DBPDE-dA adduct, and the corresponding isotope-labeled internal standards were performed; LC-MS/MS methods were used for their quantification. BRBE significantly (p < 0.05) increased cellular GSH by 31% and 13% at 6 and 24 h, respectively, in OSCC cells; in MSK-LeuK1 cells, the levels of GSH significantly (p < 0.05) increased by 55% and 22%, at 1 and 6 h. Since BRBE significantly enhanced the synthesis of GSH in both cell types, subsequent experiments were performed in MSK-Leuk1 cells. Western blot analysis was performed to determine the types of proteins involved in the synthesis of GSH. BRBE significantly (p < 0.05) increased the protein expression (2.5-fold) of the glutamate-cysteine ligase catalytic subunit (GCLC) but had no effect on the glutamate-cysteine ligase modifier subunit (GCLM) and glutathione synthetase (GSS). LC-MS/MS analysis showed that pretreatment of cells with BRBE followed by DBPDE significantly (p < 0.05) increased the levels of DBPDE-GSH conjugate (2.5-fold) and decreased DNA damage by 74% measured by assessing levels of DBPDE-dA adduct formation. Collectively, the results of this in vitro study clearly support our hypothesis, and the LC-MS/MS methods developed in the present study will be highly useful in testing the same hypothesis initially in our mouse model and ultimately in smokers.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Boca , Rubus , Humanos , Ratones , Animales , Carcinógenos , Crisenos , Benzopirenos/metabolismo , Compuestos Epoxi , Nicotiana/metabolismo , Glutamato-Cisteína Ligasa , Aductos de ADN , Cromatografía Liquida , Estuarios , Neoplasias de la Boca/inducido químicamente , Espectrometría de Masas en Tándem , Glutatión/metabolismo , Extractos Vegetales/farmacología
7.
J Org Chem ; 87(24): 16276-16296, 2022 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-36459435

RESUMEN

Reaction of 6-nitrochrysene with ethyl isocyanoacetate in the presence of a non-nucleophilic base gave a c-annulated pyrrole ethyl ester that was used to prepare chrysene-fused tripyrranes and a chrysopyrrole dialdehyde. Chrysene-fused tripyrranes were reacted with a pyrrole dialdehyde, but poor yields of chrysoporphyrins were obtained. However, condensation of the chrysopyrrole dialdehyde with a series of tripyrranes afforded excellent yields of chrysoporphyrins and an acenaphtho-chrysoporphyrin. Iron(III) chloride mediated oxidative cyclization of a dihexylchrysoporphyrin afforded a benzopyrene-fused porphyrin that exhibited a strongly red-shifted electronic absorption spectrum. DFT calculations show that both chrysoporphyrins and the benzopyrene-fused porphyrin have tautomers that possess 34π electron delocalization pathways that pass through the porphyrin nucleus and the fused polycyclic aromatic hydrocarbon (PAH) units. Protonation gave dications that favor 36-atom 34π electron circuits. c-Annulated pyrrole dialdehydes were also condensed with a carbatripyrrin to generate PAH-fused carbaporphyrins that retained fully aromatic properties.


Asunto(s)
Crisenos , Porfirinas , Compuestos Férricos , Benzopirenos , Benzo(a)pireno
8.
J Org Chem ; 87(2): 1559-1563, 2022 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-35014253

RESUMEN

We have developed robust, operationally simple syntheses of fluorenes and of dibenzo[g,p]chrysenes through oxidative cascade processes. These structures that are commonly encountered in optoelectronic materials, dyes, and pharmaceutical products are accessible from 1,4-dioxaspiro[4.5]decan-8-one. The reactions are conducted open to air with inexpensive, safe CuBr2 or CuCl2.


Asunto(s)
Crisenos , Fluorenos , Oxidación-Reducción , Estrés Oxidativo
9.
Org Biomol Chem ; 20(44): 8657-8661, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36281731

RESUMEN

A palladium-catalyzed bay-region annulative π-extension reaction of o-halobiphenyls with o-chloropyridinecarboxylic acids was developed. The reaction was carried out with a 1 : 1 ratio of substrates. A variety of azatriphenylene derivatives could be synthesized by this approach. This transformation could be applied to the synthesis of ionic liquid-crystalline molecules.


Asunto(s)
Compuestos Aza , Paladio , Paladio/química , Catálisis , Crisenos
10.
Molecules ; 27(20)2022 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-36296506

RESUMEN

Smoked cheeses are particularly popular among consumers for their flavor and aroma. Of interest, therefore, is the health aspect related to the likelihood of polycyclic aromatic hydrocarbons (PAHs), which are known carcinogens found in smoked products. Thus, the purpose of this study was to evaluate the occurrence of 15 polycyclic aromatic hydrocarbons (PAHs) in smoked and non-smoked cheeses purchased in Poland to monitor their safety. The level of selected PAHs in cheese samples was determined using the HPLC-DAD-FLD method. Most of the cheeses tested met the maximum level of benzo[a]pyrene (2 µg/kg) and the sum of benz[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene (12 µg/kg) established for these products. However, all the cheeses studied in this work had relatively low amounts of the sum of these compounds compared to the information available in the cheese literature, ranging from

Asunto(s)
Queso , Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Hidrocarburos Policíclicos Aromáticos/análisis , Crisenos , Humo , Cromatografía Líquida de Alta Presión , Benzo(a)pireno/análisis , Polonia , Acenaftenos , Fluorenos , Carcinógenos , Antracenos
11.
Water Sci Technol ; 84(10-11): 2737-2748, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34850690

RESUMEN

Polyaromatic hydrocarbons (PAHs) are uncharged, non-polar molecules generated from natural and anthropogenic activities, where the emissions from anthropogenic activities predominate. Chrysene is a high molecular weight PAH, which is found to be highly recalcitrant and mutagenic in nature. The aim of this study was to isolate chrysene-degrading microorganisms from oil-contaminated water and to enhance their degradative conditions using design expert. From the various samples collected, 19 bacterial strains were obtained through enrichment culture and the one which showed highest activity was identified by 16S rRNA sequencing as Bacillus halotolerans. Under optimum conditions of 100 mg/L chrysene concentration, 1,000 mg/L nitrogen source, and pH 6, B. halotolerans exhibited 90% chrysene degradation on sixth day. Positive results for the enzymes laccase and catechol 1,2 dioxygenase confirmed the ability for chrysene degradation by the isolated strain. Major metabolic intermediate determined in gas chromatography-mass spectrometry (GCMS) analysis was diisooctyl phthalate. Hence it can be concluded that B. halotolerans can be a promising candidate for the removal of high molecular weight (HMW) hydrocarbons from contaminated environments.


Asunto(s)
Crisenos , Hidrocarburos Policíclicos Aromáticos , Bacterias/genética , Biodegradación Ambiental , ARN Ribosómico 16S/genética , Agua
12.
Toxicol Appl Pharmacol ; 396: 114995, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32251684

RESUMEN

Currently, the environmental impact of ubiquitous plastic debris triggered quite some public attention. However, the global impact of microplastic on human health is by and large either unknown or neglected. By looking at the underlying biochemical mechanisms leading to the global health threat microplastic was discovered to carry persistent organic pollutants, such as polycyclic aromatic hydrocarbons (PAH), to marine life. The effect of microplastic-ingestion in the human body remains unfortunately somewhat elusive as of yet. For this reason, we screened for compounds binding to the human estrogen receptor α (ERα) and identified the PAH compounds indeno[1,2,3-cd]pyrene (Indpy) and picene (Pice) with a high binding affinity. We applied next generation sequencing to analyze the differentially expressed genes in MCF-7 cells after treatment with Indpy and Pice. We found 8 upregulated genes: ABCC5, CCNG2, CYP1A1, DDIT4, IER3, RUNX2, STC2, and SLC7A5 and 14 downregulated genes: ADORA1, CEBPB, CELSR2, CTSD, CXCL12, KRT19, PGR, PKIB, RARA, RET, SEMA3B, SIAH2, TFAP2C, and XBP1 induced by both ligands and associated with ESR1-regulation. The altered gene expression may influence cell proliferation and metastasis, favoring cancer development with a poor response to therapy. In addition, we confirmed the binding of Indpy and Pice to ERα using molecular docking and microscale thermophoresis. ERα activation was measured with ESR1-overexpressing HEK293 (HEK-ESR1) cells and confirmed for Indpy. In conclusion, we showed an ESR1-mediated influence of the PAH compounds Indpy and Pice on the gene expression pattern of MCF-7 cells, possibly also promoting breast cancer development in patients.


Asunto(s)
Crisenos/farmacología , Receptor alfa de Estrógeno/metabolismo , Expresión Génica/efectos de los fármacos , Pirenos/farmacología , Transducción de Señal/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7/efectos de los fármacos , Simulación del Acoplamiento Molecular , Reacción en Cadena en Tiempo Real de la Polimerasa
13.
Chem Res Toxicol ; 33(7): 1997-2005, 2020 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-32551527

RESUMEN

The environmental pollutant 6-nitrochrysene (6-NC) is a potent mutagen and a mammary carcinogen in rats. 6-NC is the most potent carcinogen ever tested in the newborn mouse assay. In mammalian cells, it is metabolically activated by nitroreduction and a combination of ring oxidation and nitroreduction pathways. The nitroreduction pathway yields two major adducts with 2'-deoxyguanosine (dG), one at the C8-position, N-(dG-8-yl)-6-AC, and the other at the exocyclic N2-position, 5-(dG-N2-yl)-6-AC. Here, we report the total synthesis of a site-specific oligonucleotide containing the 6-NC-derived C8 dG adduct, N-(dG-8-yl)-6-AC. Pd-catalyzed Buchwald-Hartwig cross coupling of 6-aminochrysene with protected C8-bromo-dG derivative served as the key reaction to furnish protected N-(dG-8-yl)-6-AC in 56% yield. The monomer for solid-phase DNA synthesis was prepared by its deprotection followed by conversion to the corresponding 5'-O-dimethoxytrityl 3'-phosphoramidite, which was used to synthesize a site-specifically adducted oligonucleotide. After purification and characterization, the adduct-containing oligonucleotide was incorporated into a plasmid and replicated in human embryonic kidney (HEK) 293T cells, which showed that N-(dG-8-yl)-6-AC stalls DNA replication as evidenced by 77% translesion synthesis (TLS) efficiency relative to the control and that the adduct is mutagenic (mutation frequency (MF) 17.8%) inducing largely G→T transversions. We also investigated the roles of several translesion synthesis DNA polymerases in the bypass of N-(dG-8-yl)-6-AC using siRNA knockdown approach. TLS efficiency was reduced in hPol η-, hPol κ-, hPol ζ-, and hREV1-deficient HEK 293T cells to 66%, 45%, 37%, and 32%, respectively. Notably, TLS efficiency was reduced to 18% in cells with concurrent knockdown of hPol κ, hPol ζ, and REV1, suggesting that these three polymerases play critical roles in bypassing N-(dG-8-yl)-6-AC. MF increased to 23.1% and 32.2% in hPol κ- and hREV1-deficient cells, whereas it decreased to 11.8% in hPol ζ-deficient cells. This suggests that hPol κ and hREV1 are involved in error-free TLS of this lesion, whereas hPol ζ performs error-prone bypass.


Asunto(s)
Crisenos/administración & dosificación , Aductos de ADN , Oligonucleótidos/administración & dosificación , Replicación del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , Células HEK293 , Humanos
14.
Ecotoxicol Environ Saf ; 200: 110780, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32470683

RESUMEN

A green synthesis method for nanoscale silver using ß-cyclodextrin as both reducing agent and stabilizer was developed. ß-cyclodextrin was used not only as a reducing agent but also a stabilizing agent for nano-silver, and is also an excellent detection substrate due to its special structure (inner hydrophobic and outer hydrophilic ring structure). Then, the green synthesized silver nanoparticles were used as Surface-enhanced Raman spectroscopy (SERS) enhanced substrates to detect polycyclic aromatic hydrocarbons, such as: anthracene, pyrene, chrysene and triphenylene. The SERS substrate can be used for both quantitative detection of the four polycyclic aromatic hydrocarbons and qualitative identification of mixtures of these hydrocarbons. This synthesis method is simple and convenient, having great potential in simultaneous and rapid detection of environmental organic pollutants.


Asunto(s)
Tecnología Química Verde/métodos , Nanopartículas del Metal/química , Hidrocarburos Policíclicos Aromáticos/análisis , Plata/química , Espectrometría Raman/métodos , beta-Ciclodextrinas/química , Antracenos/análisis , Crisenos/análisis , Interacciones Hidrofóbicas e Hidrofílicas , Pirenos/análisis
15.
Int J Mol Sci ; 21(17)2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32825444

RESUMEN

At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug's safety and efficacy; many are poorly soluble, poorly bioavailable drugs. Current tools to reformulate antiviral APIs into safer and more bioavailable forms include pharmaceutical salts and cocrystals, even though it is difficult to classify solid forms into these regulatory-wise mutually exclusive categories. Pure liquid salt forms of APIs, ionic liquids that incorporate APIs into their structures (API-ILs) present all the advantages that salt forms provide from a pharmaceutical standpoint, without being subject to solid-state matter problems. In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different.


Asunto(s)
Aciclovir/química , Antivirales/química , Betacoronavirus/efectos de los fármacos , Butiratos/química , Crisenos/química , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Aciclovir/farmacología , Antivirales/farmacología , Disponibilidad Biológica , Butiratos/farmacología , COVID-19 , Química Farmacéutica/métodos , Crisenos/farmacología , Reposicionamiento de Medicamentos/métodos , Humanos , Líquidos Iónicos/química , Pandemias , Triterpenos Pentacíclicos , SARS-CoV-2 , Solubilidad , Tratamiento Farmacológico de COVID-19
16.
Molecules ; 25(4)2020 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-32093302

RESUMEN

A new 2,7,10,15-tetraethynyldibenzo[g,p]chrysene ligand (1) and two tetranuclear gold(I) derivatives containing PPh3 (3) and PMe3 (4) phosphines were synthesized and characterized by 1H and 31P NMR, IR spectroscopy, and high-resolution mass spectrometry. The compounds were studied in order to analyze the effect of the introduction of gold(I) on the supramolecular aggregation and photophysical properties. Absorption and emission spectra displayed broad bands due to the establishment of π π interactions as an indication of intermolecular contacts and the formation of aggregates. A decrease of the recorded quantum yield (QY) of the gold(I) derivatives was observed compared to the uncomplexed ligand. The introduction of the complexes into poly methyl methacrylate (PMMA) and Zeonex 480R matrixes was analyzed, and an increase of the measured QY of 4 in Zeonex was observed. No phosphorescent emission was detected.


Asunto(s)
Crisenos/química , Oro/química , Luminiscencia , Compuestos Orgánicos de Oro , Procesos Fotoquímicos , Compuestos Orgánicos de Oro/síntesis química , Compuestos Orgánicos de Oro/química
17.
Environ Geochem Health ; 42(8): 2485-2494, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31264041

RESUMEN

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


Asunto(s)
Benzo(a)pireno/metabolismo , Contaminantes del Suelo/metabolismo , Benzo(a)pireno/química , Biodegradación Ambiental , Crisenos/química , Crisenos/metabolismo , Fluorenos/química , Fluorenos/metabolismo , Hordeum/metabolismo , Fenantrenos/química , Fenantrenos/metabolismo , Hidrocarburos Policíclicos Aromáticos/química , Hidrocarburos Policíclicos Aromáticos/metabolismo , Pirenos/química , Pirenos/metabolismo , Federación de Rusia , Suelo/química , Contaminantes del Suelo/química
18.
Environ Geochem Health ; 42(9): 2853-2863, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32166521

RESUMEN

The total mean ∑[Formula: see text] in samples were from 75.3 to 387.0 ng/g dry weight (d.w) and showed high value in black dry tea, followed by herbal, oolong, and green tea. The mean ∑[Formula: see text] (a combination of benz[a]anthracene, chrysene, benzo[b]fluoranthene, and benzo[a]pyrene) values were 54.3 ng/g, 16.4 ng/g, 14.2 ng/g, and 6.6 ng/g for black, herbal, green, and oolong teas, respectively. Concentration for benzo[a]pyrene (BaP) was from 0.4 to 35.8 ng/g, and the BaP equivalent concentration values ranged from 0.3 to 48.1 ng/g. There was only 1 black tea sample that BaP concentration exceeded the maximum level according to European Union (EU) standards. Tea samples marketed in Vietnam showed insignificant difference with the samples from other origins by same analytical method. Black teas showed high PAHs contents in dry tea samples but the released percentage of sum of PAHs from tea-to-tea infusion was lower than that in other tea type samples. The released percentages of PAH4 from tea-to-tea infusion were 40.7, 15.4, and 1.9 for green, herbal, and black tea. High temperature in black tea manufacturing processes might reduce essential oil content in tea that might effect on the PAHs partially release into the infusion. Indeed, based on EU regulations, we may conclude that tea consumers are safe in risk of exposure to PAHs obtained from teas.


Asunto(s)
Exposición Dietética/análisis , Contaminación de Alimentos/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Té/química , Benzo(a)pireno/análisis , Camellia sinensis/química , Crisenos/análisis , Exposición Dietética/efectos adversos , Fluorenos/análisis , Humanos , Hojas de la Planta/química , Medición de Riesgo/métodos , Tés de Hierbas/análisis , Vietnam
19.
Wei Sheng Yan Jiu ; 49(5): 769-774, 2020 Sep.
Artículo en Zh | MEDLINE | ID: mdl-33070822

RESUMEN

OBJECTIVE: To analyze the pollution characteristics of polycyclic aromatic hydrocarbons(PAHs) in atmospheric PM_(2. 5) in Lianhu district and Yanta district of Xi'an City. METHODS: From 2016-2018, PM_(2. 5) samples were regularly collected at monitoring points in two districts of Xi'an City, and analyzed the content of naphthalene, acenaphthylene, fluorene, acenaphthene, phenanthrene, anthracene, fluoranthene, pyrene, chrysene, benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, dibenz(a, h)anthracene, benzo(g, h, i)perylene, indeno(1, 2, 3-cd)pyrene in the samples according to Ambient air and stationary source emissions-Determination of gas and particle-phase polycyclic aromatic hydrocarbons-High performance liquid chromatography(HJ 647-2013). The test result were analyzed and evaluated according to different years, regions and seasons. RESULTS: The median total PAHs mass concentrations(ΣPAHs) in Lianhu district and Yanta district were 11. 68 and 12. 53 ng/m~3, respectively, with no significant difference(P>0. 05). The ΣPAHs of the two districts were decreasing year by year(P<0. 05). The median ΣPAHs in Lianhu district and Yanta district were highest in winter(55. 50, 55. 61 ng/m~3) and lowest in summer(4. 62, 4. 57 ng/m~3). The top three single indicators of the median PAHs in Lianhu district were benz(b)fluoranthene(1. 90 ng/m~3), benzo(g, h, i)perylene(1. 67 ng/m~3) and chrysene(1. 34 ng/m~3), In Yanta district, they were benz(b)fluoranthene(1. 95 ng/m~3), benzo(g, h, i)perylene(1. 63 ng/m~3) and pyrene(1. 47 ng/m~3). The average mass concentrations of benzo(a)pyrene in Lianhu district and Yanta district were 1. 33 ng/m~3 and 1. 10 ng/m~3, respectively. Among all the samples, the qualified samples of benzo(a)pyrene accounted for 72. 75% of the total samples, and the Lianhu district and Yanta district were 71. 20% and 74. 30%, respectively(P>0. 05). CONCLUSION: The degree of atmospheric PAHs pollution in Xi'an had decreased year by year, and PAHs pollution in winter was more serious.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Benzo(a)pireno , Cromatografía Líquida de Alta Presión , Crisenos , Contaminación Ambiental , Hidrocarburos Policíclicos Aromáticos/análisis
20.
Ecotoxicology ; 28(8): 964-972, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31414340

RESUMEN

Polyaromatic hydrocarbons are a group of chemical pollutants which cause a significant threat to the living organisms in estuaries and marine ecosystems. We report the effect of chrysene, a major PAH pollutant found in Cochin Estuary along the southwest coast of India, on the neuroendocrine and immune gene expression of the post larvae (PL-25) of Penaeus monodon. The PL- 25 of P. monodon were administered with feed coated with increasing concentrations of chrysene (1, 2 and 3 µg/g) for 10 days and the gene expression was studied on 7th, 11th and 15th day. The PL exposed to chrysene showed moulting stress and changes in the levels of moult-inhibiting hormone I (MIH I) indicated by irregular moulting in the experimental tanks. At the molecular level, the higher concentration of chrysene induced two-fold upregulation of neuroendocrine (MIH I) and downregulation of immune (ProPO and crustin) gene on the 7th day of exposure. The expression of MIH I gene reduced on withdrawing the experimental feed (on 11th day), while continued downregulation of ProPO and crustin were observed on the 11th day. The results of the present study indicate that the microgram levels of PAH can impinge the neuroendocrine and immune system of the P. monodon, which may induce morbidity and mortality to the larvae in polluted coastal ecosystems. Therefore, more attention may be given to avoid PAH pollution in the estuaries to maintain a healthy ecosystem and to protect the animals from extinction.


Asunto(s)
Crisenos/efectos adversos , Expresión Génica/efectos de los fármacos , Inmunotoxinas/efectos adversos , Neurotoxinas/efectos adversos , Penaeidae/efectos de los fármacos , Contaminantes Químicos del Agua/efectos adversos , Animales , Relación Dosis-Respuesta a Droga , Sistema Inmunológico/efectos de los fármacos , India , Sistemas Neurosecretores/efectos de los fármacos , Penaeidae/crecimiento & desarrollo , Penaeidae/inmunología , Penaeidae/fisiología
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