Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.475
Filtrar
1.
Molecules ; 26(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34684680

RESUMO

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate-good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.


Assuntos
Tiazinas , Trypanosoma brucei brucei/efeitos dos fármacos , Anidridos/química , Animais , Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Organofosfonatos/química , Tiazinas/síntese química , Tiazinas/farmacologia
2.
J Agric Food Chem ; 69(36): 10440-10449, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469128

RESUMO

The widespread application of neonicotinoid insecticides (NEOs) in agriculture causes a series of environmental and ecological problems. Microbial remediation is a popular approach to relieve these negative impacts, but the associated molecular mechanisms are rarely explored. Nitrile hydratase (NHase), an enzyme commonly used in industry for amide production, was discovered to be responsible for the degradation of acetamiprid (ACE) and thiacloprid (THI) by microbes. Since then, research into NHases in NEO degradation has attracted increasing attention. In this review, microbial degradation of ACE and THI is briefly described. We then focus on NHase evolution, gene composition, maturation mechanisms, expression, and biochemical properties with regard to application of NHases in NEO degradation for bioremediation.


Assuntos
Hidroliases , Nitrilas , Neonicotinoides , Tiazinas
3.
Cochrane Database Syst Rev ; 9: CD010062, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554571

RESUMO

BACKGROUND: This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures. Pharmacological treatment remains the first choice to control epilepsy. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we have presented a summary of evidence for the use of STM as monotherapy in epilepsy. OBJECTIVES: To assess the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug for people with epilepsy. SEARCH METHODS: We searched the following databases on 13 April 2020: the Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 10 April 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: treatment withdrawal; seizure-free at six months; adverse effects; and quality of life scoring. We conducted the primary analyses by intention-to-treat where possible, and presented a narrative analysis of the data. MAIN RESULTS: We included four studies involving a total of 355 participants: three studies (209 participants) with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS), and one study (146 participants) with a diagnosis of generalised tonic-clonic seizures (GTCS). STM was given as monotherapy compared with placebo and with levetiracetam in the BECTS studies, and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. For the primary outcome, the total number of dropouts caused either by seizure recurrence or adverse reaction was significantly higher in the levetiracetam treatment arm compared to the STM treatment arm (RR 0.32, 95% Cl 0.10 to 1.03; 1 study, 43 participants; low-certainty evidence). For the secondary outcomes for this comparison, results for seizure freedom were inconclusive (RR 1.12, 95% Cl 0.88 to 1.44; 1 study, 43 participants; low-certainty evidence). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than participants receiving phenytoin in the GTCS study (RR 0.03, 95% CI 0.00 to 0.58; 1 study, 146 participants; low-certainty evidence). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. The most common adverse events were related to behavioural disturbances when STM was compared with levetiracetam (RR 0.95, 95% Cl 0.59 to 1.55; 1 study, 43 participants; low-certainty evidence), with the same incidence in both groups. No data were reported for quality of life. Overall, we assessed one study at high risk of bias and one study at unclear bias across the seven domains, mainly due to lack of information regarding study design. Only one trial reported effective methods for blinding. The risk of bias assessments for the other two studies ranged from low to high. We rated the overall certainty of the evidence for the outcomes as low using the GRADE approach. AUTHORS' CONCLUSIONS: This review provides insufficient information to inform clinical practice. Small sample sizes, poor methodological quality, and lack of data on important outcome measures precluded any meaningful conclusions regarding the efficacy and tolerability of sulthiame as monotherapy in epilepsy. More trials, recruiting larger populations, over longer periods, are needed to determine whether sulthiame has a clinical use.


Assuntos
Epilepsia , Tiazinas , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Qualidade de Vida , Tiazinas/uso terapêutico
4.
BMC Ophthalmol ; 21(1): 319, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470600

RESUMO

BACKGROUND: Long-term use of topical, especially benzalkonium chloride (BAC)-preserved, antiglaucoma medications can cause a negative impact on the ocular surface. The aim of the study was to assess the effect of topical carbonic anhydrase inhibitors (CAIs) on selected oxidative stress biomarkers in the tear film. METHODS: The patients were divided into four sex-matched groups: group C (n = 25) - control group - subjects who did not use topical antiglaucoma medications, group DL (n = 14) - patients using preservative-free dorzolamide, group DL + BAC (n = 16) - patients using topical BAC-preserved dorzolamide, group BL + BAC (n = 17) - patients using BAC-preserved brinzolamide. Subjects in all the study groups have been using the eye drops two times daily for 6-12 months. The oxidative stress biomarkers in the tear film samples were measured: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). RESULTS: The advanced oxidation protein products content, Total Oxidant Status as well as superoxide dismutase and catalase activities in the group DL + BAC and BL + BAC were higher in comparison with the group C. The total sulfhydryl groups content was lower in the group DL + BAC and BL + BAC when compared to group C. Oxidative Stress Index was higher in the groups DL + BAC and BL + BAC in comparison with the groups DL and C. CONCLUSIONS: Use of topical benzalkonium chloride-preserved carbonic anhydrase inhibitors increases oxidative stress in the tear film.


Assuntos
Compostos de Benzalcônio , Inibidores da Anidrase Carbônica , Compostos de Benzalcônio/farmacologia , Biomarcadores , Humanos , Soluções Oftálmicas , Estresse Oxidativo , Sulfonamidas , Tiazinas , Tiofenos
5.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576043

RESUMO

The functional expression of the cockroach Pameα7 nicotinic acetylcholine receptor subunit has been previously studied, and was found to be able to form a homomeric receptor when expressed in Xenopus laevis oocytes. In this study, we found that the neonicotinoid insecticide imidacloprid is unable to activate the cockroach Pameα7 receptor, although thiacloprid induces low inward currents, suggesting that it is a partial agonist. In addition, the co-application or 5 min pretreatment with 10 µM imidacloprid increased nicotine current amplitudes, while the co-application or 5 min pretreatment with 10 µM thiacloprid decreased nicotine-evoked current amplitudes by 54% and 28%, respectively. This suggesting that these two representatives of neonicotinoid insecticides bind differently to the cockroach Pameα7 receptor. Interestingly, the docking models demonstrate that the orientation and interactions of the two insecticides in the cockroach Pameα7 nAChR binding pocket are very similar. Electrophysiological results have provided evidence to suggest that imidacloprid and thiacloprid could act as modulators of the cockroach Pameα7 receptors.


Assuntos
Inseticidas/farmacologia , Neonicotinoides/farmacologia , Antagonistas Nicotínicos/farmacologia , Nitrocompostos/farmacologia , Tiazinas/farmacologia , Animais , Baratas/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Técnicas de Patch-Clamp , Receptores Nicotínicos , Xenopus laevis
6.
Environ Pollut ; 289: 117892, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34385134

RESUMO

Thiacloprid is a neonicotinoid insecticide widely exploited in agriculture and easily mobilized towards aquatic environments by atmospheric agents. However, little information about its toxicological effects on aquatic invertebrate bioindicators is available. In this study, specimens of the mussel Mytilus galloprovincialis were exposed to thiacloprid at environmental (4.5 µg L-1) and 100 times higher than environmental (450 µg L-1) concentrations for 20 days. Thiacloprid affected haemolymph biochemical parameters, cell viability in the digestive gland, antioxidant biomarkers and lipid peroxidation in the digestive gland and gills at environmentally relevant concentrations (4.5 µg L-1). In addition, thiacloprid exposure caused histological damage to the digestive gland and gills. Interestingly, the pesticide was detected at levels equal to 0.14 ng g-1 in the soft tissues of sentinels exposed for 20 days to 450 µg L-1 thiacloprid in seawaterµ. Due to its harmful potential and cumulative effects after long-term exposure of M. galloprovincialis, thiacloprid may pose a potential risk to nontarget aquatic organisms, as well as to human health. This aspect requires further in-depth investigation.


Assuntos
Mytilus , Tiazinas , Poluentes Químicos da Água , Animais , Biomarcadores , Brânquias , Humanos , Neonicotinoides/toxicidade , Tiazinas/toxicidade , Poluentes Químicos da Água/toxicidade
7.
Water Res ; 203: 117493, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365194

RESUMO

Developing strategies to identify the origins of contaminants in watersheds is crucial for source water protection. The use of multiple tracers improves the ability to identify contamination events originating from various land use activities. The objective of this study was to evaluate the use of acesulfame and chloride as co-tracers to represent the impact of pollution originating from wastewater and road de-icing on water quality in a municipal drinking water source. The study included a two-year sampling and water quality analysis program in numerous locations within a drinking water reservoir comprising a lake (upstream) and a river (downstream) which supply raw water to a municipal water treatment plant. Results showed that the spatial variability of acesulfame and chloride within the watershed of the lake-river systems depends on the location of contaminant sources, mainly municipal wastewater and septic tank discharges (for acesulfame) and the presence of small tributaries of the lake and river (for chloride). Temporal variability of the tracers under study differed according to the sampling location and was mainly affected by seasonal conditions. Correlation analyses between the two tracers in lake and river waters (in terms of concentrations and loads) made it possible to pinpoint the probable origins of contamination. The assessment of the spatio-temporal variability of these co-tracers within the lake-river watersheds allowed for the delineation of priority intervention zones as a decision-making tool for municipal authorities in improving drinking water source protection.


Assuntos
Água Potável , Poluentes Químicos da Água , Cloretos , Monitoramento Ambiental , Tiazinas , Águas Residuárias , Poluentes Químicos da Água/análise
8.
J Vet Intern Med ; 35(5): 2196-2204, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34464464

RESUMO

BACKGROUND: Diagnosis of gastric ulcers by methods other than gastroscopy in dogs has been problematic for many years and biomarkers such as serum gastrin (SG) concentrations have been introduced as a noninvasive way to evaluate gastric diseases. OBJECTIVES: To determine the time course changes in hematology, SG concentrations, and gastroscopic images of meloxicam-induced gastric ulceration in dogs and identify a relationship between SG and gastroscopic image analysis in a clinical setting. ANIMALS: Fifteen crossbreed dogs. METHODS: Two groups: control (n = 5) and meloxicam-treated (n = 10). The meloxicam-treated group received meloxicam 0.2 mg/kg PO for 15 days. Clinical signs, hematology, SG, and image analysis (PI, pixel intensity; ID, integrated density; RA, relative area; and UI, ulcer index) of the gastroscopic examination were evaluated across time (T5, time 5 day; T10, time 10 day; and T15, time 15 day). RESULTS: Significant changes were observed among 3 time points and between the 2 groups in terms of SG, hematology, and gastroscopic image analysis. In the meloxicam-treated group, decreases in hemoglobin concentration, red blood cell count and packed cell volume at T10 and T15 (P = .0001) were observed, whereas SG, ID, and UI increased over time (P < .0001). The PI decreased significantly (P = .0001) in the meloxicam-treated group compared to controls. Significant correlations were found between SG and PI, and ID and ulcer area (r = -0.89, 0.81, 0.64), respectively. CONCLUSION AND CLINICAL IMPORTANCE: Gastroscopy is the gold standard for early descriptive diagnosis of gastric ulcerations in dogs, and SG is a good indicator for meloxicam-induced gastric ulcers in dogs and can predict the gastroscopic score of the lesion.


Assuntos
Doenças do Cão , Hematologia , Úlcera Gástrica , Tiazinas , Animais , Doenças do Cão/induzido quimicamente , Doenças do Cão/diagnóstico , Cães , Gastrinas , Gastroscopia/veterinária , Meloxicam , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/veterinária , Tiazinas/efeitos adversos , Tiazóis/efeitos adversos
9.
Molecules ; 26(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34443360

RESUMO

Plasma proteins play a fundamental role in living organisms. They participate in the transport of endogenous and exogenous substances, especially drugs. 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts, have been synthesized as potential anticancer substances used for cancer treatment. Most anticancer substances generate a toxic effect on the human body. In order to check the toxicity and therapeutic dosage of these chemicals, the study of ligand binding to plasma proteins is very relevant. The present work presents the first comparative analysis of the binding of one of the 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium derivatives (Salt1) with human serum albumin (HSA), α-1-acid glycoprotein (AGP) and human gamma globulin (HGG), assessed using fluorescence, UV-Vis and CD spectroscopy. In order to mimic in vivo ligand-protein binding, control normal serum (CNS) was used. Based on the obtained data, the Salt1 binding sites in the tertiary structure of all plasma proteins and control normal serum were identified. Both the association constants (Ka) and the number of binding site classes (n) were calculated using the Klotz method. The strongest complex formed was Salt1-AGPcomplex (Ka = 7.35·104 and 7.86·104 mol·L-1 at excitation wavelengths λex of 275 and 295 nm, respectively). Lower values were obtained for Salt1-HSAcomplex (Ka = 2.45·104 and 2.71·104 mol·L-1) and Salt1-HGGcomplex (Ka = 1.41·104 and 1.33·104 mol·L-1) at excitation wavelengths λex of 275 and 295 nm, respectively, which is a positive phenomenon and contributes to the prolonged action of the drug. Salt1 probably binds to the HSA molecule in Sudlow sites I and II; for the remaining plasma proteins studied, only one binding site was observed. Moreover, using circular dichroism (CD), fluorescence and UV-Vis spectroscopy, no effect on the secondary and tertiary structures of proteins in the absence or presence of Salt1 has been demonstrated. Despite the fact that the conducted studies are basic, from the scientific point of view they are novel and encourage further in vitro and in vivo investigations. As a next part of the study (Part 2), the second new synthetized quinobenzothiazine derivative (Salt2) will be analyzed and published.


Assuntos
Proteínas Sanguíneas/metabolismo , Análise Espectral , Tiazinas/química , Tiazinas/metabolismo , Proteínas Sanguíneas/química , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Termodinâmica
10.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360585

RESUMO

New, tricyclic compounds containing a sulfonyl moiety in their structure, as potential safer COX inhibitors, were designed and synthesized. New derivatives have three conjugated rings and a sulfonyl group. A third ring, i.e., an oxazine, oxazepine or oxazocin, has been added to the 1,2-benzothiazine skeleton. Their anti-COX-1/COX-2 and cytotoxic effects in vitro on NHDF cells, together with the ability to interact with model membranes and the influence on reactive oxygen species and nitric oxide, were studied. Additionally, a molecular docking study was performed to understand the binding interaction of the compounds with the active site of cyclooxygenases. For the abovementioned biological evaluation of new tricyclic 1,2-benzothiazine derivatives, the following techniques and procedures were employed: the differential scanning calorimetry, the COX colorimetric inhibitor screening assay, the MTT, DCF-DA and Griess assays. All of the compounds studied demonstrated preferential inhibition of COX-2 compared to COX-1. Moreover, all the examined tricyclic 1,2-thiazine derivatives interacted with the phospholipid model membranes. Finally, they neither have cytotoxic potency, nor demonstrate significant influence on the level of reactive oxygen species or nitric oxide. Overall, the tricyclic 1,2-thiazine derivatives are good starting points for future pharmacological tests as a group of new anti-inflammatory agents.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Derme/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tiazinas/química , Anti-Inflamatórios não Esteroides/química , Células Cultivadas , Inibidores de Ciclo-Oxigenase/química , Derme/citologia , Fibroblastos/citologia , Humanos , Simulação de Acoplamento Molecular , Prostaglandina-Endoperóxido Sintases/química
11.
Antimicrob Agents Chemother ; 65(11): e0058321, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34370580

RESUMO

Multiple drug discovery initiatives for tuberculosis are currently ongoing to identify and develop new potent drugs with novel targets in order to shorten treatment duration. One of the drug classes with a new mode of action is DprE1 inhibitors targeting an essential process in cell wall synthesis of Mycobacterium tuberculosis. In this investigation, three DprE1 inhibitors currently in clinical trials, TBA-7371, PBTZ169, and OPC-167832, were evaluated side-by-side as single agents in the C3HeB/FeJ mouse model presenting with caseous necrotic pulmonary lesions upon tuberculosis infection. The goal was to confirm the efficacy of the DprE1 inhibitors in a mouse tuberculosis model with advanced pulmonary pathology and perform comprehensive analysis of plasma, lung, and lesion-centric drug levels to establish pharmacokinetic-pharmacodynamic (PK-PD) parameters predicting efficacy at the site of infection. Results showed significant efficacy for all three DprE1 inhibitors in the C3HeB/FeJ mouse model after 2 months of treatment. Superior efficacy was observed for OPC-167832 even at low-dose levels, which can be attributed to its low MIC, favorable distribution, and sustained retention above the MIC throughout the dosing interval in caseous necrotic lesions, where the majority of bacteria reside in C3HeB/FeJ mice. These results support further progression of the three drug candidates through clinical development for tuberculosis treatment.


Assuntos
Mycobacterium tuberculosis , Tiazinas , Tuberculose , Animais , Camundongos , Camundongos Endogâmicos C3H , Piperazinas , Tuberculose/tratamento farmacológico
12.
Nat Commun ; 12(1): 4671, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344863

RESUMO

Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest and apoptosis of TNBC cells. In vivo, 108600 treatment of mice bearing triple negative tumors results in the induction of apoptosis and overcomes chemotherapy resistance. Finally, treatment with 108600 and chemotherapy suppresses growth of pre-established TNBC metastases, providing additional support for the clinical translation of this agent to clinical trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Nitrobenzenos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Tiazinas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Caseína Quinase II/antagonistas & inibidores , Caseína Quinase II/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Células-Tronco Neoplásicas/patologia , Nitrobenzenos/química , Nitrobenzenos/farmacologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/química , Tiazinas/química , Tiazinas/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Environ Res ; 200: 111721, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293312

RESUMO

The coloured dyes released from the textile industrial effluents into water resources cause non-aesthetic pollution and aquatic life toxicity. Thus textile waste water treatment has been studied globally for many years. Photocatalytic properties of lead tungstate (PbWO4) nanoparticles (NPs) were analyzed for thiazine dyes and textile waste water under ultraviolet light conditions. XRD result showed the tetragonal scheelite structure of PbWO4 NPs. The crystallinity of the sample was confirmed from the SAED and XRD pattern. The existence of stretch vibration of Pb-O and O-W-O confirmed from FTIR results. EDAX displays optical absorption signals of Pb, W and O, and confirm the formation of PbWO4. Optical studies reveal that the band gap of the obtained nanoparticles increases with respect to their bulk counterparts that may be attributed to reduction in particle size. TEM images of PbWO4 powder consists of hexagonal particles and relatively uniform and smooth surface rod shaped prism-like structures. The photocatalytic activity of the prepared nanoparticles was analyzed through the degradation of textile waste water under UV light irradiation. The photocatalytic reaction rate constant was found to be 0.014/min. The small sized PbWO4 particles can adsorb more OH groups and oxidatively degrade the pollutants in the textile waste water.


Assuntos
Nanopartículas , Tiazinas , Poluentes Químicos da Água , Catálise , Corantes , Têxteis , Águas Residuárias , Poluentes Químicos da Água/análise
14.
Water Res ; 202: 117454, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34332189

RESUMO

The artificial sweetener Acesulfame (ACE) has been frequently detected in wastewater treatment plants (WWTPs) and is regarded as an emerging pollutant due to its low biodegradability. However, recent observations of ACE biodegradation in WWTPs have stimulated interest in the ACE-degrading bacteria and mineralization pathways. In this study, next-generation sequencing methods, Illumina and Nanopore sequencing, were combined to explore the ACE-degrading communities enriched from the activated sludge of six municipal wastewater treatment plants. Metagenomic investigations indicated that all enrichments were similarly dominated by the phyla Proteobacteria and Planctomycetes. Notably, at the species level, four metagenome-assembled genomes (MAGs) were shared by six enriched communities with considerable abundances, indicating that they may be responsible for ACE biodegradation in the enrichments. Besides, two ACE-degrading pure strains, affiliated to the genus Chelatococcus, were isolated from the enrichment. The genomic analysis showed that these two isolates were the new species that were genetically distinct from their relatives. Two type strains, Chelatococcus asaccharovorans DSM 6462 and Chelatococcus composti DSM 101465, could not degrade ACE, implying that the ACE-degrading capability was not shared among the different species in the genus Chelatococcus. The results of the degradation experiment showed that the two isolates could use ACE as the sole carbon source and mineralize ~90% of the total organic carbon. Three biotransformation products (TP96, TP180B, and TP182B) were demonstrated by UPLC-QTOF-MS. The results of this study provide valuable insights into ACE biodegradation and its biotransformation products.


Assuntos
Genômica , Edulcorantes , Alphaproteobacteria , Biodegradação Ambiental , Cinética , Tiazinas
15.
Biomed Res Int ; 2021: 9967035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34258285

RESUMO

Nonnutritive sweeteners (NNSs) are sugar substitutes widely used to reduce the negative health effects of excessive sugar consumption. Dental caries, one of the most prevalent chronic diseases globally, results from a pathogenic biofilm with microecological imbalance and frequent exposure to sugars. Some research has shown that certain NNSs possess less cariogenic potential than sucrose, indicating their putative effect on oral microbiome. To uncover the alterations of acidogenic pathogens and alkali-generating commensals, as well as the biofilm cariogenic potential under the influence of NNSs, we selected four common NNSs (acesulfame-K, aspartame, saccharin, and sucralose) and established single-, dual-, and multispecies in vitro culture model to assess their effects on Streptococcus mutans (S. mutans) and/or Streptococcus sanguinis (S. sanguinis) compared to sucrose with the same sweetness. The results showed that NNSs significantly suppressed the planktonic growth, acid production, and biofilm formation of S. mutans or S. sanguinis compared with sucrose in single-species cultures. Additionally, decreased S. mutans/S. sanguinis ratio, less EPS generation, and higher pH value were observed in dual-species and saliva-derived multispecies biofilms with supplementary NNSs. Collectively, this study demonstrates that NNSs inhibit the cariogenic potential of biofilms by maintaining microbial equilibrium, thus having a promising prospect as anticaries agents.


Assuntos
Cárie Dentária/prevenção & controle , Diterpenos do Tipo Caurano/química , Microbiota , Boca/microbiologia , Adoçantes não Calóricos , Aspartame/análise , Biofilmes/efeitos dos fármacos , Cariogênicos/farmacologia , Cárie Dentária/etiologia , Glicosídeos/metabolismo , Humanos , Hibridização in Situ Fluorescente , Proteínas de Plantas/química , Sacarina/análise , Streptococcus mutans , Streptococcus sanguis , Sacarose/análogos & derivados , Sacarose/análise , Tiazinas/análise
16.
Molecules ; 26(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065194

RESUMO

Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 µM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 µM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.


Assuntos
Acetamidas/síntese química , Acetamidas/farmacologia , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/síntese química , Hipoglicemiantes/farmacologia , Tiazinas/química , Tiazinas/farmacologia , Acetamidas/química , Acetamidas/uso terapêutico , Simulação por Computador , Diabetes Mellitus/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Tiazinas/síntese química
17.
J Am Vet Med Assoc ; 259(1): 84-87, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34125605

RESUMO

OBJECTIVE: To determine the pharmacokinetics of meloxicam in Wyandotte hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1 mg of meloxicam/kg [0.45 mg of meloxicam/lb]) and compare results with those previously published for White Leghorn hens. ANIMALS: 8 healthy adult Wyandotte hens. PROCEDURES: Hens were administered 1 mg of meloxicam/kg, PO, once. A blood sample was collected immediately before and at intervals up to 48 hours after drug administration. The hens' eggs were collected for 3 weeks after drug administration. Samples of the hens' plasma and egg whites (albumen) and yolks were analyzed with high-performance liquid chromatography. RESULTS: Mean ± SD terminal half-life, maximum concentration, and time to maximum concentration were 5.53 ± 1.37 hours, 6.25 ± 1.53 µg/mL, and 3.25 ± 2.12 hours, respectively. Mean ± SD number of days meloxicam was detected in egg whites and yolks after drug administration was 4.25 ± 2 days and 9.0 ± 1.5 days, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with White Leghorn hens, meloxicam in Wyandotte hens had a longer terminal half-life, greater area under the plasma concentration-versus-time curve from time 0 to infinity, a smaller elimination rate constant, and a longer mean residence time-versus-time curve from time 0 to infinity, and drug persisted longer in their egg yolks. Therefore, the oral dosing interval of meloxicam may be greater for Wyandotte hens. Results may aid veterinarians on appropriate dosing of meloxicam to Wyandotte hens and inform regulatory agencies on appropriate withdrawal times.


Assuntos
Galinhas , Tiazinas , Administração Oral , Animais , Anti-Inflamatórios não Esteroides , Área Sob a Curva , Feminino , Meia-Vida , Meloxicam , Óvulo , Tiazóis
18.
Int Ophthalmol ; 41(9): 3191-3198, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34114138

RESUMO

PURPOSE: To evaluate the effect of topical prophylaxis with brinzolamide-brimonidine fixed combination on short-term intraocular pressure (IOP) elevation after intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF). METHODS: This prospective comparative study included 56 eyes of 47 patients treated with intravitreal injections of anti-VEGF, and they were randomly divided into two groups. In control group (25 eyes), no prophylactic medication was used, whereas in case group (31 eyes) one drop of a fixed combination of brinzolamide-brimonidine was instilled two hours before the injection. IOP was measured before the injection and at 1 min, 10 min and 30 min post-injection in all eyes. RESULTS: The mean IOP before injection at 1 min, 10 min and 30 min post-injection was 16,6 ± 2,8 mmHg, 53,4 ± 12 mmHg, 26,4 ± 5,5 mmHg and 17,9 ± 4 mmHg, respectively, in control group and 15,1 ± 3,4 mmHg, 42,6 ± 8,4 mmHg, 21,4 ± 5,5 mmHg and 12,4 ± 3,5 mmHg, respectively, in case group. At 1 min, 10 min and 30 min post-injection, the mean IOP was significantly lower in case group compared with control group (p < 0,001, p = 0,0014 and p < 0,0001, respectively), but no difference at the pre-injection IOP between the two groups was found (p = 0,09). CONCLUSIONS: The prophylactic administration of one drop of brinzolamide-brimonidine fixed combination significantly reduces the IOP spikes during the first 30 min after the intravitreal anti-VEGF injection.


Assuntos
Pressão Intraocular , Hipertensão Ocular , Tartarato de Brimonidina/uso terapêutico , Humanos , Injeções Intravítreas , Hipertensão Ocular/tratamento farmacológico , Estudos Prospectivos , Sulfonamidas , Tiazinas
19.
Food Chem ; 359: 129936, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33957328

RESUMO

In this work, new selective and sensitive dual-template molecularly imprinted polymer nanoparticles (MIPs) were synthesized and characterized. Sorbent MIPs were investigated for simultaneous extraction and clean-up of thiamethoxam and thiacloprid from light and dark honey samples. In this study, ultra-high-performance liquid chromatography-tandem mass spectrometry triple-quadrupole (UHPLC-MS/MS) (QQQ) was used to detect and quantify the pesticides. The kinetic model with adsorption kinetics of sorbent was investigated. The optimal adsorption conditions were 80 mg of polymer MIPs, a 30-min extraction time, and a pH of 7. The detection limit (LOD) and the quantification limit (LOQ) varied from 0.045 to 0.070 µg kg-1 and from 0.07 to 0.10 µg kg-1, respectively. The intra-day and inter-day precision (RSD, %) ranged from 1.3 to 2.0% and from 8.2 to 12.0%, respectively. The recovery of thiamethoxam and thiacloprid ranged from 96.8 to 106.5% and 95.3 to 104.4%, respectively, in light and dark honey samples.


Assuntos
Mel/análise , Fenômenos Magnéticos , Impressão Molecular/métodos , Nanopartículas/química , Neonicotinoides/isolamento & purificação , Praguicidas/isolamento & purificação , Polímeros/química , Tiametoxam/isolamento & purificação , Tiazinas/isolamento & purificação , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Limite de Detecção , Magnetismo , Polímeros Molecularmente Impressos , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos
20.
Acta Chim Slov ; 68(1): 151-158, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34057526

RESUMO

Phytoalexins are substances with antimicrobial properties produced by plants after being attacked by microorganisms, especially phytopathogenic fungi and viruses. They are also currently being studied for their antitumor effect. We aimed to study the apoptosis-stimulating effect of homobrassinin and thiazino[6,5-b]indol in human ovarian adenocarcinoma A2780 and A2780cis cells via flow cytometric analysis of annexin V/PI, caspase 3 and 9 activity, cytochrome C release, and smac-diablo accumulation. Using the western blot technique, we also monitored the effect of both indoles on the response of heat shock proteins in these cells. Thiazino[6,5-b]indol showed more pronounced sensitizing and/or pro-apoptotic effect compared to homobrassinin accompanied by increased smac-diablo accumulation at earlier time intervals and pronounced externalization of phosphatidylserine at 72 h in A2780cis compared to A2780 cells. The apoptosis stimulating effect of thiazino[6,5-b]indol in A2780cis cells was associated with significant irreversible downregulation of HSP70 and HSP90 and partly with a decrease of HSP40. On the other hand, cisplatin-induced the apoptosis of sensitive A2780 cells with reversible downregulation of HSP40 and HSP57. In conclusion, the effect of thiazino[6,5-b]indol on resistant A2780cis cells could have a great utility in both the potential prevention and the treatment of other cisplatin-resistant tumor cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Indóis/farmacologia , Tiazinas/farmacologia , Tiocarbamatos/farmacologia , Anexina A5/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Citocromos c/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...