Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28.927
Filtrar
1.
Braz. j. biol ; 84: e253948, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355909

RESUMO

Abstract The assessment of the comparative effect of biosal (phytopesticide), deltamethrin, and lambda-cyhalothrin (pyrethroids) were made against two fodder pests, Hermolaus modestus and Hermolaus ocimumi by filter paper impregnation method. The activity of total protein contents, GPT (glutamic-pyruvic transaminase) and GOT (glutamic oxaloacetate transaminase) were affected in Hermolaus modestus and Hermolaus ocimumi against biosal, deltamethrin, and lambda cyhalothrin. The activity of total protein contents in H. modestus was 31.053%, 4.607%, and 24.575%, against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The activity of total protein contents was observed as 24.202%, 15.25%, and 56.036% against deltamethrin, lambda-cyhalothrin, and biosal, respectively in H. ocimumi. The activity of GOT was observed as 98.675% for biosal 33.95% for deltamethrin and 83.619% for lambda-cyhalothrin in H. modestus. The GOT activity was estimated in H. ocimumi as 78.831%, 47.645%, and 71.287% against biosal, deltamethrin, and lambda-cyhalothrin, respectively. The efficacy of GPT enzyme against biosal, deltamethrin, and lambda-cyhalothrin was calculated as 89.26%, 73.07%, and 47.58%, respectively in H. modestus. The H. ocimumi showed GPT activity as 77.58% for biosal, 68.84% for deltamethrin, and 52.67% for lambda-cyhalothrin, respectively.


Resumo A avaliação do efeito comparativo do biosal (fitopesticida), deltametrina e lambda-cialotrina (piretróides) foi feita contra duas pragas forrageiras, Hermolaus modestus e Hermolaus ocimumi, pelo método de impregnação com papel de filtro. A atividade do conteúdo de proteína total, GPT (transaminase glutâmico-pirúvica) e GOT (oxaloacetato transaminase glutâmico) foram afetados em Hermolaus modestus e Hermolaus ocimumi contra biosal, deltametrina e lambda cialotrina. A atividade do conteúdo de proteína total em H. modestus foi 31.053%, 4.607% e 24.575%, contra biosal, deltametrina e lambda-cialotrina, respectivamente. A atividade do conteúdo de proteína total foi observada como 24.202%, 15.25% e 56,036% contra deltametrina, lambda-cialotrina e biosal, respectivamente em H. ocimumi. A atividade do GOT foi observada em 98.675% para o biosal, 33,95% para a deltametrina e 83.619% para a lambda-cialotrina em H. modestus. A atividade do GOT foi estimada em H. ocimumi como 78.831%, 47.645% e 71.287% contra biosal, deltametrina e lambda-cialotrina, respectivamente. A eficácia da enzima GPT contra biosal, deltametrina e lambda-cialotrina foi calculada como 89.26%, 73.07% e 47.58%, respectivamente em H. modestus. A H. ocimumi apresentou atividade GPT de 77.58% para biosal, 68.84% para deltametrina e 52.67% para lambda-cialotrina, respectivamente.


Assuntos
Animais , Piretrinas , Inseticidas , Heterópteros , Alanina Transaminase , Ração Animal , Nitrilas
2.
J Hazard Mater ; 441: 129952, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36116312

RESUMO

The insecticide flonicamid (FLO) and its main degradation intermediate 4-trifluoromethylnicotinamide (TFNA-AM) are hazardous to the environment and animals. Microbial transformation of FLO has been well studied, but no study has yet reported on TFNA-AM degradation by a microorganism. Here, Pseudomonas stutzeri CGMCC 22915 effectively degraded TFNA-AM to 5-trifluoromethylnicotinic acid (TFNA). P. stutzeri CGMCC 22915 degraded 60.0% of TFNA-AM (1154.44 µmol/L) within 6 h with a half-life of just 4.5 h. Moreover, P. stutzeri CGMCC 22915 significantly promoted TFNA-AM decomposition in surface water. The reaction was catalyzed by an amidase, PsAmiA. PsAmiA is encoded in a novel nitrile-converting enzyme gene cluster. The enzyme shared only 20-44% identities with previously characterized signature amidases. PsAmiA was successfully expressed in Escherichia coli and its enzymatic properties were investigated using TFNA-AM as the substrate. PsAmiA was more active toward amides without hydrophilic groups, and did not hydrolyze another amide metabolite of FLO, N-(4-trifluoromethylnicotinoyl)glycinamide (TFNG-AM), which is structurally very similar to TFNA-AM. Molecular docking of PsAmiA and TFNA-AM indicated that hydrophobic residues Leu148, Ala150, Ala195, Ile225, Trp341, Leu460, and Ile463 may affect its substrate spectrum. This study provides new insights of the environmental fate of FLO at the molecular level and the structure-function relationships of amidases.


Assuntos
Inseticidas , Amidas , Amidoidrolases/genética , Animais , Inseticidas/química , Simulação de Acoplamento Molecular , Niacinamida/análogos & derivados , Nitrilas , Água
3.
J Hazard Mater ; 441: 129871, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36067561

RESUMO

Highly efficient single atom catalysts are critical to substantially promote for peroxymonosulfate (PMS) activation to organic pollutant degradation, but it remains a challenge at present. Herein, single atom Mn anchored on N-doped porous carbon (SA-Mn-NSC) was synthesized by ball milling of Mn-doped carbon nitride and spirulina biochar to dominantly activate PMS. The precursor of carbon nitride and spirulina possessed a strong coordinating capability for Mn(II), facilitating the formation of highly dispersed nitrogen-coordinated Mn sites (Mn-N4). The SA-Mn-NSC catalyst exhibited high activity and stability in the heterogeneous activation of PMS to degrade a wide range of pollutants within 10 min, showing an outstanding degradation rate constant of 0.31 min-1 in enrofloxacin (ENR) degradation. The high surface density of Mn-N4 sites and abundant interconnected meso-macro pores were highly favorable for activating PMS to produce 1O2 and high-valent manganese (Mn(IV)) for pollutant degradation. This work offers a new pathway of using a low-cost and easily accessible single-atom catalysts (SACs) and could inspire more catalytic oxidation strategies.


Assuntos
Poluentes Ambientais , Spirulina , Carbono , Catálise , Enrofloxacina , Manganês , Nitrilas , Nitrogênio , Peróxidos , Porosidade
4.
J Colloid Interface Sci ; 630(Pt B): 900-910, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36356455

RESUMO

HYPOTHESIS: The superiority of graphitic carbon nitride (g-C3N4) nanosheet results from its large specific surface area, which can be achieved by exfoliation of the bulk layered structure. Liquid-phase exfoliation (LPE) is the best-known method for the synthesis of two-dimensional (2D) g-C3N4 nanosheets. However, experimental investigations do not allow for a molecular-level understanding of the process. Molecular dynamics (MD) simulations are expected to provide microscopic insights and quantitative evaluation of the energy consumption during LPE, thus facilitating the search of effective solvents for the LPE of 2D materials. SIMULATIONS: MD simulations are carried out to simulate the LPE process by performing potential of mean force calculations for the separation of two stacked g-C3N4 nanosheets. Free energy of exfoliation is evaluated and compared among nine common solvents with distinct molecular structures. FINDINGS: The most probable path for the exfoliation process is identified. The free energy of exfoliation is found to correlate directly with the solvent free energy of a single g-C3N4 nanosheet. The solvation is enthalpy-driven and affected by the mobility of the solvent molecules around the nanosheet. Based on the MD results, several strategies are proposed to guide the selection of solvents for effective LPE.


Assuntos
Grafite , Simulação de Dinâmica Molecular , Nitrilas/química , Grafite/química , Compostos de Nitrogênio/química
5.
J Colloid Interface Sci ; 631(Pt A): 25-34, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36370496

RESUMO

The emergence of widespread microbial contamination and drug-resistant bacteria in the water environment poses a severe threat to public health. Photocatalysis is considered an efficient, energy-saving, and cost-effective disinfection strategy for effectively removing microbial contamination from water bodies. In this paper, a metal-free O-doped g-C3N4/carbon dots (O-CN/CDs) nanosheet photocatalysts are prepared in coordination with various modification strategies, which results in a considerable improvement in photocatalytic disinfection activity compared to bulk g-C3N4 (B-CN). First, O-doping and morphology modulation are achieved simultaneously with hydrothermal treatment, which not only hinders the recombination of photogenerated hole-electron pairs, but also enables the exposure of more active centers. Subsequently, loading of CDs onto O-CN nanosheets by electrostatic self-assembly increases the production of photogenerated hole-electron pairs by expanding the visible light absorption region and promoted the separation of photogenerated carriers by trapping photogenerated electrons. Interestingly, the loading of CDs changes the charge on the surface of the composite photocatalyst from negative to positive, making it easier for the active species to come in contact with bacteria, and thus improving bacterial disinfection performance. Under visible light irradiation, the inactivation efficiency of optimized O-CN/CDs against methicillin-resistant Staphylococcus aureus (MRSA) is log(C/C0) = 4.08, approximately 9 times higher than that of B-CN. The main active species inactivating bacteria are superoxide anions radicals (•O2-) and photogenerated holes, and their attack causes damage to the membrane wall structure and leakage of intracellular components. Additionally, the feasibility of the as-prepared photocatalysts in water disinfection in real environments was confirmed by photocatalytic disinfection experiments in successive recovery cycles and in practical lake water.


Assuntos
Desinfecção , Staphylococcus aureus Resistente à Meticilina , Desinfecção/métodos , Catálise , Carbono/farmacologia , Água , Nitrilas/química , Bactérias
6.
Chemosphere ; 311(Pt 1): 136925, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36283432

RESUMO

Antibiotic abuse will seriously affect the ecology and environment. Photocatalytic oxidation technology based on carbon nitride (g-C3N4) has been widely adopted to treat wastewater containing antibiotics. Here, a novel composite photocatalyst MCNT was prepared by loading manganese oxide (Mn3O4) on the surface of g-C3N4 nanotubes (CNT). Three typical antibiotics, trimethoprim (TMP), norfloxacin (NOR), and tetracycline (TC) were used as model contaminants to evaluate the oxidative properties of prepared materials. Compared with bulk g-C3N4, the degradation rates of TMP, NOR, and TC catalyzed by MCNT-5 were increased by 2, 3, and 1.4 times, respectively, mainly due to 1) the larger specific surface area of the nanotube structure of CNT, which provides abundant active sites for antibiotic adsorption and catalytic oxidation, and 2) the loading of Mn3O4, which promotes the directional migration of photogenerated charges and improves the separation efficiency of photogenerated electrons and holes. The free radical capture and quenching experiments confirmed that MCNT degraded the target organic pollutants with hydroxyl radical (·OH) and singlet oxygen (1O2) as the main active oxidants. This catalyst maintained 80% photocatalytic oxidation performance after five cyclic experiments. This study provides new insights into developing efficient, stable, and environmentally-friendly photocatalysts and provides a new dimension to mitigate the antibiotic pollution problem.


Assuntos
Nanotubos de Carbono , Antibacterianos/química , Água , Nitrilas/química , Catálise , Tetraciclina
7.
J Environ Sci (China) ; 125: 37-46, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375922

RESUMO

Photooxidative removal of pharmaceuticals and organic dyes is an effective way to eliminate growing micropollutants. However, photooxidation often results in byproducts as secondary hazardous substances such as phytotoxins. Herein, we found that photooxidation of common antibiotic tetracycline hydrochloride (TCH) over a metal-free 8-hydroxyquinoline (8-HQ) functionalized carbon nitride (CN) photocatalyst significantly reduces the TCH phytotoxic effect. The phytotoxicity test of photocatalytic treated TCH-solution evaluated towards seed growth of Cicer arietinum plant model endowed natural root and shoot growth. This study highlights the conceptual insights in designing of metal-free photocatalyst for environmental remediation.


Assuntos
Oxiquinolina , Tetraciclina , Tetraciclina/toxicidade , Oxiquinolina/toxicidade , Nitrilas/toxicidade , Antibacterianos/toxicidade , Metais
8.
Food Chem ; 404(Pt A): 134594, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36265272

RESUMO

Brassica vegetables are frequently consumed foods of nutritional interest, because they are rich in glucosinolates (GLSs). Among GLS breakdown products, especially isothiocyanates are known for their health-beneficial effects, while nitriles are less beneficial. To increase the understanding of the plant matrix's influence on GLS degradation, differently concentrated vegetable broths were prepared from selected Brassica vegetables (kohlrabi and red cabbage) and subsequently boiled. Altogether, heat stability and conversion of GLSs to the corresponding nitriles were both strongly influenced by vegetable type and plant matrix concentration in the broths. After boiling kohlrabi broths for 120 min, recovery of 4-(methylthio)butyl-GLS as nitrile was 55.5 % in 1 g/mL broth and 8.4 % in 0.25 g/mL broth. In follow-up experiments, a pronounced influence of the matrix's redox status was identified, with H2S being an important factor. A better understanding of these processes will help to preserve health-promoting effects of GLSs in Brassica vegetables in the future.


Assuntos
Brassica , Glucosinolatos , Glucosinolatos/análise , Brassica/metabolismo , Verduras/metabolismo , Nitrilas/metabolismo , Oxirredução
10.
Food Chem ; 398: 133884, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964575

RESUMO

Development of selective and sensitive methods for the detection of 2, 6-dipicolinic acid (DPA), a biomarker produced by bacterial spores, is of great significance for maintaining public health and food safety. Herein, a ratiometric fluorescence strategy using graphene carbon nitride (g-C3N4) coupled with Eu3+ is designed for the assay of DPA. As the concentration of DPA increases, the emission intensity of g-C3N4 kept constant which acted as a stable internal reference, while the fluorescence of Eu3+ was enhanced obviously due to the antenna effect. The linear calibration ranged from 0.1 to 15 µM with a detection limit of 13 nM was obtained. More Importantly, a paper-based sensor with a smartphone was successfully combined to perform colorimetric and visual detection of DPA in situ. This method has good performance for the detection of DPA, which is expected to broaden the application prospects of preliminary biomarker monitoring.


Assuntos
Antraz , Antraz/diagnóstico , Antraz/microbiologia , Biomarcadores , Európio , Corantes Fluorescentes , Humanos , Nitrilas , Ácidos Picolínicos , Smartphone
11.
J Photochem Photobiol B ; 237: 112589, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36399823

RESUMO

Fluorescent probes offer incredibly effective tools for visualizing the dynamic morphology of lipid droplets (LDs) and investigating their physiological interactions. In this work, we have utilized solvatochromic coumarin probes bearing nitrile and ester substituents for live-cell imaging. The fluorescence probes are characterized by a donor (diethylamino) and acceptor (nitrile and/or ester) substituents and a rotatable double bond. The designed architecture allows investigation of environmental sensitivity apart from providing excellent ability to target sub-cellular organelles. The synthesized fluorophores showed low cytotoxicity and excellent localization within the lipid droplets. Further, the fluorophores were also utilized to study viscosity changes within the LDs induced by Nystatin. More importantly, we also demonstrate imaging of LDs in multi-cellular animal models such as C. elegans.


Assuntos
Corantes Fluorescentes , Gotículas Lipídicas , Animais , Caenorhabditis elegans , Cumarínicos , Nitrilas , Ésteres
12.
J Phys Chem B ; 126(44): 8957-8969, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36317866

RESUMO

We present a multifaceted approach to effectively probe complex local protein environments utilizing the vibrational reporter unnatural amino acid (UAA) 4-cyano-l-phenylalanine (pCNPhe) in the model system superfolder green fluorescent protein (sfGFP). This approach combines temperature-dependent infrared (IR) spectroscopy, X-ray crystallography, and molecular dynamics (MD) simulations to provide a molecular interpretation of the local environment of the nitrile group in the protein. Specifically, a two-step enantioselective synthesis was developed that provided an 87% overall yield of pCNPhe in high purity without the need for chromatography. It was then genetically incorporated individually at three unique sites (74, 133, and 149) in sfGFP to probe these local protein environments. The incorporation of the UAA site-specifically in sfGFP utilized an engineered, orthogonal tRNA synthetase in E. coli using the Amber codon suppression protocol, and the resulting UAA-containing sfGFP constructs were then explored with this approach. This methodology was effectively utilized to further probe the local environments of two surface sites (sites 133 and 149) that we previously explored with room temperature IR spectroscopy and X-ray crystallography and a new interior site (site 74) featuring a complex local environment around the nitrile group of pCNPhe. Site 133 was found to be solvent-exposed, while site 149 was partially buried. Site 74 was found to consist of three distinct local environments around the nitrile group including nonspecific van der Waals interactions, hydrogen-bonding to a structural water, and hydrogen-bonding to a histidine side chain.


Assuntos
Fenilalanina , Aminoácidos , Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/química , Hidrogênio , Nitrilas/química , Fenilalanina/química
13.
Crit Rev Oncol Hematol ; 180: 103862, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36332787

RESUMO

Myelofibrosis (MF) is a clonal hematologic malignancy with progressive bone marrow fibrosis. Clinical manifestations of MF include splenomegaly, constitutional symptoms, and anemia, whose pathogenesis is multifactorial and largely due to ineffective erythropoiesis and is clinically associated with poor quality of life and reduced overall survival. The only curative treatment for MF is allogenic stem cell transplantation; however, few patients are eligible. Disease management strategies for MF-related anemia have limited effectiveness, and Janus kinase (JAK) inhibitors may induce or worsen related anemia. Thus, there is a significant unmet need for the treatment of patients with MF-related anemia. This review summarizes current and emerging treatments for anemia in MF, including luspatercept and KER-050 (transforming growth factor-ß ligand traps), momelotinib and pacritinib (JAK inhibitors), pelabresib (a bromodomain extra-terminal domain inhibitor), PRM-151 (an antifibrotic agent), imetelstat (a telomerase inhibitor), and navitoclax (a BCL-2/BCL-xL inhibitor). Therapeutic combinations with ruxolitinib may offer another treatment approach.


Assuntos
Anemia , Antineoplásicos , Mielofibrose Primária , Humanos , Mielofibrose Primária/complicações , Mielofibrose Primária/terapia , Janus Quinase 2 , Qualidade de Vida , Nitrilas/uso terapêutico , Anemia/terapia , Anemia/tratamento farmacológico , Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
14.
Molecules ; 27(22)2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36432142

RESUMO

Glucosinolates, specialized metabolites of the Brassicales including Brassica crops and Arabidopsis thaliana, have attracted considerable interest as chemical defenses and health-promoting compounds. Their biological activities are mostly due to breakdown products formed upon mixing with co-occurring myrosinases and specifier proteins, which can result in multiple products with differing properties, even from a single glucosinolate. Whereas product profiles of aliphatic glucosinolates have frequently been reported, indole glucosinolate breakdown may result in complex mixtures, the analysis of which challenging. The aim of this study was to assess the breakdown of indole glucosinolates in A. thaliana root and rosette homogenates and to test the impact of nitrile-specifier proteins (NSPs) on product profiles. To develop a GC-MS-method for quantification of carbinols and nitriles derived from three prominent indole glucosinolates, we synthesized standards, established derivatization conditions, determined relative response factors and evaluated applicability of the method to plant homogenates. We show that carbinols are more dominant among the detected products in rosette than in root homogenates of wild-type and NSP1- or NSP3-deficient mutants. NSP1 is solely responsible for nitrile formation in rosette homogenates and is the major NSP for indolic nitrile formation in root homogenates, with no contribution from NSP3. These results will contribute to the understanding of the roles of NSPs in plants.


Assuntos
Arabidopsis , Arabidopsis/metabolismo , Glucosinolatos/química , Metanol/metabolismo , Nitrilas/química , Indóis/metabolismo
15.
Eur J Cancer ; 177: 33-44, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36323051

RESUMO

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) patients with positive AR-V7 expression in their circulating tumour cells (CTCs) rarely derive benefit from abiraterone and enzalutamide. DESIGN: We performed a prospective, multicenter, single arm phase II clinical trial (CABA-V7) in mCRPC patients previously treated with docetaxel and androgen deprivation therapy. OBJECTIVE: In this trial, we investigated whether cabazitaxel treatment resulted in clinically meaningful PSA response rates in patients with positive CTC-based AR-V7 expression and collected liquid biopsies for genomic profiling. RESULTS: Cabazitaxel was found to be modestly effective, with only 12% of these patients obtaining a PSA response. Genomic profiling revealed that CTC-based AR-V7 expression was not associated with other known mCRPC-associated alterations. CTC-based AR-V7 status and dichotomised CTC counts were observed as independent prognostic markers at baseline. CONCLUSIONS: AR-V7 positivity predicted poor overall survival (OS). However, cabazitaxel-treated AR-V7 positive patients and those lacking AR-V7 positivity, who received cabazitaxel as standard of care, appeared to have similar OS. Therefore, despite the low response rate, cabazitaxel may still be an effective treatment in this poor prognosis, AR-V7 positive patient population.


Assuntos
Células Neoplásicas Circulantes , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/patologia , Antígeno Prostático Específico , Receptores Androgênicos/metabolismo , Antagonistas de Androgênios/uso terapêutico , Isoformas de Proteínas/genética , Células Neoplásicas Circulantes/patologia , Nitrilas/uso terapêutico
16.
Org Biomol Chem ; 20(46): 9192-9206, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36354143

RESUMO

From the array of small molecule organic fluorophores available as functional materials and in biology, synthetic procedures that allow for a simpler and rapid synthesis of organic fluorophores with desirable photophysical properties are in high demand. In addition, fluorophores with good brightness and tuneability in both solid and solution states are only available in certain numbers. Herein, we introduce a new family of pyrrolo[2,1-a]isoindolylidene-malononitrile (PIYM) fluorophores that exhibit pronounced emission in the visible region in solution and red-NIR emission in the solid state, with tuneability, efficient brightness and stability. PIYM fluorophores were efficiently synthesized via two simple MCR reaction pathways from commercially available, as well as newly synthesized, building blocks. Furthermore, the observed photophysical nature is rationalized from both electrochemical and theoretical calculations (DFT and TD-DFT). In the future, we anticipate that these PIYM fluorophores, with their excellent stability and lower molecular weight, will open ways to enhance the development of NIR-emitting fluorophores with more significant applications in both materials and biological fields.


Assuntos
Corantes Fluorescentes , Nitrilas , Corantes Fluorescentes/química , Ionóforos
17.
J Chromatogr A ; 1686: 463647, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36413910

RESUMO

In this study, the untargeted screening of the degradation products of chlorothalonil (CHT) in vegetables was performed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Sulfhydryl-CHT (SH-CHT) and hydroxyl CHT (OH-CHT) were screened as the key degradation products of CHT in vegetables. SH-CHT is a new degradation product of CHT in the vegetables. This study was the first discover the SH-substituted degradation product of pesticide in vegetables. The chemical structure of SH-CHT was deduced and confirmed through synthetic reference. An efficient method for the simultaneous monitoring of SH-CHT and hydroxyl CHT (OH-CHT) in vegetables has been proposed based on QuEChERS in combination with HPLC-MS/MS analysis. The recoveries of SH-CHT and OH-CHT were in range of 85.8%-105.1% with intra- and inter-relative standard deviation (RSD) of less than 10.0%. The limits of detection were 2.0 µg/kg for SH-CHT and 0.2 µg/kg for OHCHT. Seven kinds of vegetables covering various plant families were processed with CHT. As a result, SH-CHT was detected in five kinds of sulfur-rich vegetables with transformation rates of 7.6%-26.6%. OH-CHT was detected in all the vegetables with transformation rates of 1.7%-14.0%. Toxicity evaluation based on ECOSAR program indicated that SH-CHT had potentially high toxicity to aquatic organisms. This study provides a powerful approach for the monitoring and risk assessment of SH-CHT and OH-CHT in food safety control. Furthermore, the study inspires comprehensive research on the overlooked degradation pathways of pesticides in sulfur-rich vegetables.


Assuntos
Praguicidas , Verduras , Espectrometria de Massas em Tandem , Nitrilas/toxicidade , Enxofre
18.
Biomolecules ; 12(11)2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36421730

RESUMO

Bicalutamide (BCL) is a nonsteroidal antiandrogen drug that represents an alternative to castration in the treatment of prostate cancer, due to its relatively long half-life and tolerable side effects. However, it possesses a very low water solubility that can affect its oral bioavailability. In this work, we developed inclusion complexes of BCL with the highly soluble hydroxypropyl-ß-cyclodextrin (HP-ß-CyD) and sulfobutylether-ß-cyclodextrin (SBE-ß-CyD) to increase the water solubility and anticancer activity of BCL. The inclusion complexes were prepared using the freeze-drying method and were then characterized in a solid state via differential scanning calorimetry and X-ray analysis and in solution via phase-solubility studies and UV-vis and NMR spectroscopy. The BCL/HP-ß-CyD and BCL/SBE-ß-CyD inclusion complexes were amorphous and rapidly dissolved in water. Both the 1H-NMR spectra and molecular modeling studies confirmed the penetration of the 2-(trifluoromethyl)benzonitrile ring of BCL within the cavity of both cyclodextrins (CyDs). Due to the consistent improvement of the water solubility of BCL, the inclusion complexes showed higher antiproliferative activity toward the human prostate androgen-independent cell lines, DU-145 and PC-3, with respect to free BCL. These results demonstrate the ability of HP-ß-CyD and SBE-ß-CyD to complex BCL, permitting the realization of liquid formulations with potentially high oral bioavailability and/or possible parenteral administration.


Assuntos
Ciclodextrinas , Masculino , Humanos , Ciclodextrinas/farmacologia , Ciclodextrinas/química , Nitrilas/farmacologia , Solubilidade , 2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Água/química
19.
Int J Mol Sci ; 23(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36430948

RESUMO

Rhodesain is a cysteine protease that is crucial for the life cycle of Trypanosoma brucei rhodesiense, a parasite causing the lethal form of Human African Trypanosomiasis. CD24 is a recently developed synthetic inhibitor of rhodesain, characterized by a nanomolar affinity towards the trypanosomal protease (Ki = 16 nM), and acting as a competitive inhibitor. In the present work, we carried out a combination study of CD24 with curcumin, the multitarget nutraceutical obtained from Curcuma longa L., which we demonstrated to inhibit rhodesain in a non-competitive manner. By applying the Chou and Talalay method, we obtained an initial additive effect at IC50 (fa = 0.5, Combination Index = 1), while for the most relevant fa values, ranging from 0.6 to 1, i.e., from 60% to 100% of rhodesain inhibition, we obtained a combination index < 1, thus suggesting that an increasingly synergistic action occurred for the combination of the synthetic inhibitor CD24 and curcumin. Furthermore, the combination of the two inhibitors showed an antitrypanosomal activity better than that of CD24 alone (EC50 = 4.85 µM and 10.1 µM for the combination and CD24, respectively), thus suggesting the use of the two inhibitors in combination is desirable.


Assuntos
Curcumina , Trypanosoma brucei rhodesiense , Humanos , Curcumina/farmacologia , Dipeptídeos , Nitrilas , Cisteína Endopeptidases , Combinação de Medicamentos , Antígeno CD24
20.
J Org Chem ; 87(22): 15312-15326, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36343221

RESUMO

Herein, we report an elemental sulfur-promoted switchable redox condensation reaction that can selectively prepare 2-aminofurans and 2-aminothiophenes from the corresponding enaminones and methylene nitriles, respectively. Mechanistic studies demonstrated that the enaminones, as dual nucleophiles, reacted with nitrile acetate to produce 2-aminofurans via 3,5-annulation under promotion by elemental sulfur. These reactions used readily available starting materials, transition metal-free, eco-friendly procedures, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of 2-aminofuran and 2-aminothiophene derivatives with potential biological activity.


Assuntos
Nitrilas , Enxofre , Metano , Oxirredução
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...