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1.
J Chromatogr A ; 1663: 462784, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-34974370

RESUMO

With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-ß-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC50 values of 0.43 ± 0.03, 0.46 ± 0.02, 0.50 ± 0.03 and 0.51 ± 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs.


Assuntos
Terminalia , Acetilcolinesterase , Animais , Celulose , Inibidores da Colinesterase , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Enzimas Imobilizadas , Frutas , Espectrometria de Massas , Simulação de Acoplamento Molecular , Extratos Vegetais , Reprodutibilidade dos Testes
2.
Anal Chim Acta ; 1191: 339362, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35033267

RESUMO

Herein, the Ru-N-C nanozymes with abundant active Ru-Nx sites have been successfully prepared by pyrolyzing Ru(acac)3 trapped zeolitic-imidazolate-frameworks (Ru(acac)3@ZIF-8). Taking advantages of the remarkable peroxidase-mimicking activity, outstanding stability and reusability of Ru-N-C nanozymes, a novel biosensing system with explicit mechanism is strategically fabricated for sensitively determining acetylcholinesterase (AChE) and tacrine. The limit of detection for AChE activity can achieve as low as 0.0433 mU mL-1, and the IC50 value of tacrine for AChE is about 0.190 µmol L-1. The robust analytical performance in serums test verifies the great application potential of this assay in real matrix. Furthermore, "INH" and "IMPLICATION-AND" logic gates are rationally constructed based on the proposed colorimetric sensor. This work not only provides one sustainable and effective avenue to fabricate Ru-N-C-based peroxidase mimic with high catalytic performance, and also gives new impetuses for developing novel biosensors by applying Ru-N-C-based enzyme mimics as substitutes for the natural enzyme.


Assuntos
Técnicas Biossensoriais , Colorimetria , Acetilcolinesterase , Catálise , Peroxidases
3.
Psychopharmacology (Berl) ; 239(1): 59-81, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35013761

RESUMO

RATIONALE: Depression is often associated with memory impairment, a clinical feature of Alzheimer's disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. OBJECTIVES: The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. METHODS: ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1ß, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. RESULTS: 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. CONCLUSIONS: These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.


Assuntos
Quinolinas , Selênio , Acetilcolinesterase/metabolismo , Animais , Depressão/tratamento farmacológico , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Camundongos , Estresse Oxidativo , Sistema Hipófise-Suprarrenal/metabolismo , Quinolinas/farmacologia
4.
J Mol Graph Model ; 110: 108069, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34773872

RESUMO

Chiral organophosphorus agents are distributed ubiquitously in the environment, but the neuroactivity of these asymmetric chemicals to humans remains uncertain. This scenario was to explore the stereoselective neurobiological response of human acetylcholinesterase (AChE) to chiral pyraclofos at the enantiomeric scale, and then decipher the microscopic basis of enantioselective neurotoxicity of pyraclofos enantiomers. The results indicated that (R)-/(S)-pyraclofos can form the bioconjugates with AChE with a stoichiometric ratio of 1:1, but the neuronal affinity of (R)-pyraclofos (K = 6.31 × 104 M-1) with AChE was larger than that of (S)-pyraclofos (K = 1.86 × 104 M-1), and significant enantioselectivity was existed in the biochemical reaction. The modes of neurobiological action revealed that pyraclofos enantiomers were situated at the substrate binding domain, and the strength of the overall noncovalent bonds between (S)-pyraclofos and the residues was weaker than that of (R)-pyraclofos, resulting in the high inhibitory effect of (R)-pyraclofos toward the activity of AChE. Dynamic enantioselective biointeractions illustrated that the intervention of inherent conformational flexibility in the AChE-(R)-pyraclofos was greater than that of the AChE-(S)-pyraclofos, which arises from the big spatial displacement and the conformational flip of the binding domain composed of the residues Thr-64~Asn-89, Gly-122~Asp-134, and Thr-436~Tyr-449. Energy decomposition exhibited that the Gibbs free energies of the AChE-(R)-/(S)-pyraclofos were ΔG° = ï¼37.4/-30.2 kJ mol-1, respectively, and the disparity comes from the electrostatic energy during the stereoselective neurochemical reactions. Quantitative conformational analysis further confirmed the atomic-scale computational chemistry conclusions, and the perturbation of (S)-pyraclofos on the AChE's ordered conformation was lower than that of (R)-pyraclofos, which is germane to the interaction energies of the crucial residues, e.g. Tyr-124, Tyr-337, Asp-74, Trp-86, and Tyr-119. Evidently, this attempt will contribute mechanistic information to uncovering the neurobiological effects of chiral organophosphates on the body.


Assuntos
Acetilcolinesterase , Simulação de Dinâmica Molecular , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase , Humanos , Simulação de Acoplamento Molecular , Organotiofosfatos , Análise Espectral , Estereoisomerismo
5.
Pest Manag Sci ; 78(1): 274-286, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34480397

RESUMO

BACKGROUND: Elevated CO2 can directly affect the toxicity of insecticides to insects and the physiological response of insects to insecticides. Frankliniella occidentalis and F. intonsa are highly destructive pests that target horticultural crops. Spinetoram is an effective pesticide against thrips. This study sought to explore the effect of elevated CO2 on efficacy of spinetoram against F. occidentalis and F. intonsa and effect of the spinetoram on activities of protective and detoxifying enzymes under elevated CO2 . Notably, these enzymes can be exploited in further studies to develop interventions for thrips resistance management. RESULTS: Toxicity bioassay showed that the LC50 values of F. occidentalis and F. intonsa exposed to spinetoram at elevated CO2 (800 µL L-1 concentration) for 48 h was 0.08 and 0.006 mg L-1 , respectively, which is 0.62 and 0.75 times of the values at ambient CO2 (400 µL L-1 concentration). The findings showed that elevated CO2 decreased activities of the superoxide dismutase and acetylcholinesterase in thrips, while increasing the activities of carboxylesterase and glutathione S-transferase. However, spinetoram increased activities of protective and detoxifying enzymes in both thrips under the two CO2 levels. Elevated CO2 and spinetoram affect the physiological enzyme activity in thrips synergistically, and the activities of analyzed enzymes were generally higher in F. occidentalis than in F. intonsa. CONCLUSION: Elevated CO2 amplifies the efficacy of spinetoram on thrips, F. intonsa is more susceptibility to spinetoram than F. occidentalis and the latter showed better adaptation to adverse conditions than the former. © 2021 Society of Chemical Industry.


Assuntos
Dióxido de Carbono/farmacologia , Macrolídeos/farmacologia , Tisanópteros , Acetilcolinesterase , Animais , Tisanópteros/efeitos dos fármacos , Tisanópteros/enzimologia
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120412, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34597870

RESUMO

A deep eutectic solvent (DES)-based extraction method is established to facilitate the determination of methomyl in grain via enzyme inhibition fluorescence. The environmentally-friendly DES was synthesized from proline and ethylene glycol and used as a green replacement for traditional extraction solvents that are generally toxic. The DES was added to grain samples and vortex extraction of methomyl, the supernatant was then collected for fluorescence detection. Biomass carbon quantum dots (CQDs) synthesized from millet were used as fluorescent probes. Acetylcholinesterase catalyzes the hydrolysis of acetylthiocholine iodide to thiocholine. The positively-charged thiocholine interacts electrostatically with the negatively-charged quantum dots resulting in the quenching of their fluorescent emission. The pesticide extract solution blocks the enzyme activity and thus recovers the fluorescent from the quantum dots. The fluorescence response was correlated with the amount of methomyl residue in the grain over the range 0.01 to 5 mg kg-1. The limit of detection was found to be 0.003 mg kg-1, and the limit of quantification 0.01 mg kg-1. Recoveries of 86.5% to 107.8% were obtained using real samples, including millet, rice, wheat, and barley, with a relative standard deviation of less than 3.8%. The method is efficient and convenient and has good application prospects for extracting and detecting pesticides in grain samples.


Assuntos
Metomil , Pontos Quânticos , Acetilcolinesterase , Grão Comestível , Limite de Detecção , Solventes
7.
Chemosphere ; 287(Pt 4): 132434, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34606890

RESUMO

Fluoxetine (FLU), a selective serotonin reuptake inhibitor, is commonly found in aquatic environments. Ultraviolet (UV) photolysis is widely used to remove certain pharmaceuticals from water and wastewater. The present study aimed to investigate the toxicity of FLU and its transformed products formed during UV photolysis by using zebrafish embryos (Danio rerio) as a model. The degradation rates of FLU for five days were approximately 63.6% ± 2.14%, 84.6% ± 0.99%, and 97.5% ± 0.25% after 15, 30, and 60 min of UV irradiation, respectively. Furthermore, the degradation mechanism was explored using LC-MS measurements and density flooding theory (DFT) theoretical calculations. Comprehensive toxicity preassessment of FLU and its degradation products was carried out using the T.E.S.T. software. The effects of physiological and biochemical parameters and neuron- and apoptosis-related gene expression were examined in zebrafish embryos exposed to non-irradiated (0-min) and irradiated (15, 30- and 60-min) solutions from 4 h post-fertilization (hpf) to 120 hpf. The hatching time of zebrafish embryos exposed to the non-irradiated solution (0-min) and irradiated solution (60-min) was delayed, their heart rate at 48 and 72 hpf increased, and their body length at 120 hpf decreased. Significant differences were found between the non-irradiated (0-min) and UV-irradiated (15- or 30-min) groups. A dynamic response involving acetylcholinesterase (AChE) and superoxide dismutase (SOD) activity was also observed in the non-irradiated and UV-irradiated groups. During the UV treatment experiments, the expression levels of neuron-related and apoptosis-related genes were significantly reduced over time alongside the formation of FLU degradation products. Overall, this study provides new concepts to remove and assess the toxicity of emerging contaminants in aquatic environments and highlights the need to consider the formation and persistence of toxic transformation products.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Acetilcolinesterase , Animais , Antidepressivos , Embrião não Mamífero , Fluoxetina/toxicidade , Água , Poluentes Químicos da Água/toxicidade
8.
Environ Pollut ; 292(Pt A): 118333, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637829

RESUMO

While interactions with global warming and multigenerational effects are considered crucial to improve risk assessment of pesticides, these have rarely been studied in an integrated way. While heat extremes can magnify pesticide toxicity, no studies tested how their combined effects may transmit to the next generation. We exposed mosquito larvae in a full factorial, two-generation experiment to a heat spike followed by chlorpyrifos exposure. As expected, the heat spike magnified the chlorpyrifos-induced lethal and sublethal effects within both generations. Only when preceded by the heat spike, chlorpyrifos increased mortality and reduced the population growth rate. Moreover, chlorpyrifos-induced reductions in heat tolerance (CTmax), acetylcholinesterase (AChE) activity and development time were further magnified by the heat spike. Notably, when parents were exposed to chlorpyrifos, the chlorpyrifos-induced lethal and sublethal effects in the offspring were smaller, indicating increased tolerance to chlorpyrifos. In contrast, there was no such multigenerational effect for the heat spike. Despite the adaptive multigenerational effect to the pesticide, the synergism with the heat spike was still present in the offspring generation. Generally, our results provide important evidence that short exposure to pulse-like global change stressors can strongly affect organisms within and across generations, and highlight the importance of considering multigenerational effects in risk assessment.


Assuntos
Clorpirifos , Culicidae , Praguicidas , Acetilcolinesterase , Animais , Clorpirifos/toxicidade , Temperatura Alta , Larva
9.
Food Chem ; 370: 131360, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662796

RESUMO

A novel deep eutectic solvent-based extraction and sulfur-doped carbon quantum dots (S-CQDs) serving as fluorescence probes to detect pirimicarb in cereals were established. The deep eutectic solvent was synthesized using choline chloride and butanediol, achieving direct and efficient extraction of pirimicarb residue in the cereals. The fluorescence quenching of S-CQDs was caused by the electrostatic interaction between the negatively charged S-CQDs and positively charged thiocholine, which was the hydrolysate of acetylthiocholine. The fluorescence of S-CQDs was enhanced as the activity of acetylcholinesterase (AChE) was inhibited by pirimicarb, achieving the detection of pirimicarb in the cereal samples. The limit of detection (LOD) was 0.006 µg mL-1. The recovery ranged from 96.6% to 108.2%. This extraction and detection method of pirimicarb based on an environmentally friendly DES and S-CQD fluorescent sensor maintains good stability and convenience, offering a promising strategy for extracting and testing harmful substances in food samples.


Assuntos
Grão Comestível , Pontos Quânticos , Acetilcolinesterase , Carbamatos , Pirimidinas , Solventes
10.
Sci Total Environ ; 805: 150373, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34818764

RESUMO

There is increasing awareness that the toxicity of pesticides can to a large extent be modulated by warming, and that temporal exposure scenarios may strongly affect the impact of two stressors. Nevertheless, we lack information on how the exposure duration to warming may shape pesticide toxicity under warming. Furthermore, despite that bioenergetic responses have the potential to generate mechanistic insights in how toxicants interact with warming, this has been understudied in ecotoxicology. To investigate whether warming duration modifies pesticide toxicity, mosquito larvae were exposed to a control temperature at 20 °C or three warming treatments at 24 °C (acute, developmental and transgenerational warming), and to four pesticide treatments (solvent control, and three chlorpyrifos concentrations) in a full factorial design. Chlorpyrifos increased mortality, growth rate and the energy consumed, and reduced the AChE (acetylcholinesterase) activity, the energy available, and the net energy budget (estimated as cellular energy allocation). The warming treatments did not affect mortality, AChE activity, and the energy consumed. However, acute warming increased the growth rate and decreased the energy available, while both acute and developmental warming decreased the cellular energy allocation. A first key finding was that the lethal and sublethal effects of chlorpyrifos were less strong under warming because of a higher degradation in the medium under warming. A second key finding was that, among the warming treatments, the pesticide toxicity was more increased under acute warming than under transgenerational warming. This could be explained by the negative impact of acute warming but not transgenerational warming on the net energy budget. The results in this study provide mechanistic insights that the exposure duration to warming can play an important role in modulating the impact of pesticides under warming. Therefore, including ecologically relevant temporal scenarios of exposure to warming is important in ecotoxicological studies.


Assuntos
Clorpirifos , Praguicidas , Acetilcolinesterase , Animais , Clorpirifos/toxicidade , Temperatura Alta , Larva , Praguicidas/toxicidade
11.
Environ Res ; 203: 111793, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34339694

RESUMO

Considering the ecological risks of polycyclic aromatic hydrocarbons (PAHs) to the marine environment, it is urgent to find scientific and effective monitoring methods. In this study, an integrated approach combining chemical ecological risk assessment and multi-integrated biomarker indexes approach was used to assess the marine environment. Samples included seawater, sediments, and clam Ruditapes philippinarum were collected from four bays on the Shandong Peninsula, China in the four seasons of 2019. The concentrations, composition, potential sources, and ecological risk of PAHs were investigated in seawater and sediments. Risk quotient (RQ) and sediment quality guidelines (SQGs) were calculated to assess the ecological risks of PAHs in seawater and sediment, respectively. And then, clam Ruditapes philippinarum's multi-level biological response, including its ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), lipid peroxidation (LPO), and acetylcholinesterase (AChE) were investigated in-depth, by which multi-integrated biomarker indexes approach were calculated to evaluate marine environmental quality. Taken together, the results showed that the concentration of PAHs was in good agreement with the response of biomarkers, and the usefulness of the combined use of chemical ecological risk assessment and integrated biomarker indexes to assess PAHs pollution was verified.


Assuntos
Bivalves , Poluentes Químicos da Água , Acetilcolinesterase , Animais , Baías , Biomarcadores , China , Monitoramento Ambiental , Medição de Risco , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
12.
Environ Res ; 203: 111902, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34416252

RESUMO

Agricultural pesticides have been one of the most extensively used compounds throughout the world. The main sources of contamination for humans are dietary intake and occupational exposure. The impairments caused by agricultural pesticide exposure have been a significant global public health problem. Recent studies have shown that low-level agricultural pesticide exposure during the critical period of neurodevelopment (pregnancy and lactation) is closely related to autism spectrum disorder (ASD). Inhibition of acetylcholinesterase, gut microbiota, neural dendrite morphology, synaptic function, and glial cells are targets for the effects of pesticides during nervous system development. In the present review, we summarize the associations between several highly used and frequently studied pesticides (e.g., glyphosate, chlorpyrifos, pyrethroids, and avermectins) and ASD. We also discusse future epidemiological and toxicological research directions on the relationship between pesticides and ASD.


Assuntos
Transtorno do Espectro Autista , Clorpirifos , Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Acetilcolinesterase , Transtorno do Espectro Autista/induzido quimicamente , Clorpirifos/toxicidade , Feminino , Humanos , Praguicidas/toxicidade , Gravidez
13.
Bioorg Chem ; 118: 105457, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34798458

RESUMO

Substitution of hazardous and often harmful organic solvents with "green" and "sustainable" alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer's disease, Parkinson's disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC50 = 0.31 ± 0.11 µM) and monoamine oxidase B (MAO B) (IC50 = 0.34 ± 0.04 µM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC50 = 0.13 ± 0.09 µM) was the most active AChE inhibitor.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Pirimidinonas/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Pirimidinonas/síntese química , Pirimidinonas/química , Relação Estrutura-Atividade
14.
Bioorg Chem ; 118: 105479, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34801945

RESUMO

Tacrine is a known Acetylcholinesterase (AChE) inhibitors having hepatotoxicity as main liability associated with it. The present study aims to reduce its hepatotoxicity by synthesizing tacrine linked triazole glycoconjugates via Huisgen's [3 + 2] cycloaddition of anomeric azides and terminal acetylenes derived from tacrine. A series of triazole based glycoconjugates containing both acetylated (A-1 to A-7) and free sugar hydroxyl groups (A-8 to A-14) at the amino position of tacrine were synthesized in good yield taking aid from molecular docking studies and evaluated for their in vitro AChE inhibition activity as well as hepatotoxicity. All the hybrids were found to be non-toxic on HePG2 cell line at 200 µM (100 % cell viability) as compared to tacrine (35 % cell viability) after 24 h of incubation period. Enzyme kinetic studies carried out for one of the potent hybrids in the series A-1 (IC50 0.4 µM) revealed its mixed inhibition approach. Thus, compound A-1 can be used as principle template to further explore the mechanism of action of different targets involved in Alzheimer's disease (AD) which stands as an adequate chemical probe to be launched in an AD drug discovery program.


Assuntos
Acetilcolinesterase/metabolismo , Antineoplásicos/farmacologia , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Glicoconjugados/farmacologia , Tacrina/farmacologia , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicoconjugados/química , Células Hep G2 , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Tacrina/química , Triazóis/química
15.
Pestic Biochem Physiol ; 180: 104985, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34955178

RESUMO

The poultry red mite, Dermanyssus gallinae, is the most important blood sucking ectoparasite of egg laying hens and causes economic losses in poultry farms worldwide. Although various management methods exist, the control of poultry red mites (PRMs) mainly relies on acaricides such as pyrethroids and organophosphates (OPs) in many regions of the world. However, repeated use of these synthetic chemicals has resulted in resistance development causing control failure of PRM. In this study, we investigated acaricide resistance mechanisms of Turkish PRM populations. First, we obtained the COI sequence from 30 PRM populations from different regions in Turkey and identified four different COI haplotypes. Toxicity assays showed that four field-collected PRM populations were highly resistant to the pyrethroid alpha-cypermethrin, with resistance ratios (RRs) varying between 100- and 400-fold, while two of these populations had a RR of more than 24-fold against the OP acaricide phoxim. Biochemical assays showed a relatively higher activity of glutathione-S-transferases and carboxyl-cholinesterases, two well-known classes of detoxification enzymes, in one of these resistant populations. In addition, we also screened for mutations in the gene encoding the voltage-gated sodium channel (vgsc) and acetylcholinesterase 1 (ace-1), the target-site of pyrethroids and OPs, respectively. In all but two PRM populations, at least one vgsc mutation was detected. A total of four target-site mutations, previously associated with pyrethroid resistance, M918T, T929I, F1534L, F1538L were found in domain II and III of the VGSC. The T929I mutation was present in the vgsc of almost all PRM populations, while the other mutations were only found at low frequency. The G119S/A mutation in ace-1, previously associated with OP resistance, was found in PRM for the first time and present in fourteen populations. Last, both alive and dead PRMs were genotyped after pesticide exposure and supported the possible role of target-site mutations, T929I and G119S, in alpha-cypermethrin and phoxim resistance, respectively. To conclude, our study provides a current overview of resistance levels and resistance mutations in Turkish PRM populations and might aid in the design of an effective resistance management program of PRM in Turkey.


Assuntos
Acaricidas , Ácaros , Acaricidas/toxicidade , Acetilcolinesterase , Animais , Galinhas , Turquia
16.
Biosens Bioelectron ; 199: 113906, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34968952

RESUMO

Developing portable, quantitative, and user-friendly analytical tools for sensitive pesticide assay is of significant importance for guaranteeing food safety. Herein, a novel electrochemical biosensor was constructed by integrating laser-induced graphene (LIG) electrode on polyimide (PI) foil and MnO2 nanosheets loaded on the paper for point-of-care test (POCT) of organophosphorus (OPs) residues. The principle of this biosensor relied on acetylcholinesterase (AChE)-catalyzed hydrolytic product-triggered disintegration of MnO2 nanosheets for releasing assistant DNA to initiate nicking enzyme-aided recycling amplification. In the presence of OPs, the activity of AChE was inhibited and could not initiate the cleavage of the electroactive molecules-labeled hairpin probe on the electrode, resulting in the maintenance of the electrochemical response to realize a "sign-on" determination of OPs. The proposed biosensor exhibited satisfactory analytical performance for OPs assay with a linear range from 3 to 4000 ng/mL and a limit of detection down to 1.2 ng/mL. Moreover, the biosensor was useful for evaluating the residual level of pesticides in the vegetables. Therefore, this novel biosensor holds great promise for OPs assay and opens a new avenue on the development of higher-performance POCT device for sensing applications in the environment and food safety fields.


Assuntos
Técnicas Biossensoriais , Grafite , Praguicidas , Acetilcolinesterase , DNA , Lasers , Compostos de Manganês , Compostos Organofosforados , Óxidos
17.
Aquat Toxicol ; 242: 106050, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34915355

RESUMO

Shrimp aquaculture is a valuable source of quality seafood that can be impacted by exposure to insecticides, such as imidacloprid. Here, adult black tiger shrimp (Penaeus monodon) were used to evaluate the activity of acetylcholinesterase (AChE), catalase (CAT), and glutathione S-transferase (GST) in abdominal, head, gill, and hepatopancreas tissue as biomarkers for imidacloprid exposure. Adult P. monodon were continuously exposed to imidacloprid in water (5 µgL-1 and 30 µgL-1) or feed (12.5 µg g-1 and 75 µg g-1) for either 4 or 21 days. The imidacloprid concentration in shrimp tissues was determined using liquid chromatography-mass spectrometry after QuEChER extraction, and AChE, CAT, and GST activities were estimated by spectrophotometric assay. Imidacloprid exposure in shrimp elevated the activity of biomarkers, and the enzymatic activity was positively correlated to tissue imidacloprid accumulation, although the effects varied in a tissue-, dose- and time-dependent manner. AChE activity was correlated to imidacloprid concentration in the abdominal tissue of shrimp and was likely related to neural tissue distribution, while the activity of CAT and GST confirmed a generalised anti-oxidant stress response. AChE, CAT, and GST were valuable biomarkers for assessing shrimp response to imidacloprid exposure from dietary or water sources, and the abdominal tissue was the most reliable for exposure assessment. An elevated response in each of these biomarkers during routine monitoring could provide an early warning of shrimp stress, suggesting that investigating potential contamination by neonicotinoid pesticides would be worthwhile.


Assuntos
Neonicotinoides , Nitrocompostos , Penaeidae , Poluentes Químicos da Água , Acetilcolinesterase , Animais , Biomarcadores , Catalase , Exposição Ambiental , Glutationa Transferase , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Penaeidae/efeitos dos fármacos , Penaeidae/enzimologia , Poluentes Químicos da Água/toxicidade
18.
Pestic Biochem Physiol ; 180: 104984, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34955177

RESUMO

The predatory mite Neoseiulus californicus McGregor (Acari: Phytoseiidae) is an important natural enemy of phytophagous mites, and naturally established populations are often found in apple orchards. However, insecticide applications to control pests cause side effects to non-target organisms such as N. californicus. Pirimicarb, a widely used carbamate insecticide in apple orchards, is generally considered a selective aphidicide, however, toxicity to beneficial insects and predatory mites has been reported. Furthermore, the molecular basis for this selectivity, if present in N. californicus, is still largely unknown. In this study, 8 field-collected N. californicus populations were investigated and showed up to 27-fold resistance compared to a susceptible laboratory population. Selection in the laboratory for 5 consecutive generations resulted in a 69-fold pirimicarb resistance. Although there were no significant difference in terms of the acetlycholinesterase (AChE) activity between susceptible and field-collected populations, the selected population exhibited a significantly higher AChE activity. In addition, gene copy number variation of acetylcholinesterase (ace) gene among populations was detected and ranged from 1.6 to 2.1-fold relative to the susceptible population. All field-collected populations, but not the selected population, had a significantly higher ace copy number compared to the susceptible population (t-test, p < 0.05). Molecular analysis of the target-site (AChE) revealed, for the first time, a phenylalanine to tryptophan substition at position 331 in AChE (Torpedo californica numbering), both in field-collected and the selected population, but not in the susceptible population. Last, the selected F5 population consumed significantly more Tetranychusurticae adults than the parental population. Together, the results of this study shed light on the molecular determinants of acaricide selectivity in predatory mites, and will contribute to a better design of an integrated mite management program, including the use of pesticide resistant N. californicus in apple orchards.


Assuntos
Carbamatos , Resistência a Inseticidas , Ácaros , Pirimidinas , Tetranychidae , Acetilcolinesterase/genética , Animais , Variações do Número de Cópias de DNA , Inseticidas , Controle Biológico de Vetores
19.
Chemosphere ; 286(Pt 3): 131866, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34391112

RESUMO

Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Acetilcolinesterase , Animais , Metabolismo Energético , Larva , Locomoção , Músculos , Sistema Nervoso , Pirróis , Poluentes Químicos da Água/toxicidade
20.
Food Chem ; 368: 130782, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34392121

RESUMO

In this study, the aerial parts and bulbs of nine Allium species were investigated for their functional phytochemical profile, in vitro antioxidant activities, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, α-glucosidase, and tyrosinase inhibitory properties. Phenolics, alkaloids, glucosinolates and other sulfur-containing compounds were distinctively profiled in the different species. Maceration in methanol allowed recovering the highest cumulative phenolic content in A. scabrifolium (42.31 mg/g), followed by A. goekyigiti (33.15 mg/g) and A. atroviolaceum (28.35 mg/g). The aerial parts of all Allium species showed high in vitro antioxidant activity whereas methanolic extract of A. cappadocicum bulb showed the highest inhibition against AChE (2.44 mg galantamine equivalent/g) and the water extracts of A. isauricum aerial part were the best BChE inhibitors (4.31 mg galantamine equivalent/g). Bulbs were the richer source of oligosaccharides, and in vitro digestion determined an increase of oligosaccharides bioaccessibility. A promising nutraceutical potential could be highlighted in our understudied Allium species.


Assuntos
Allium , Antioxidantes , Acetilcolinesterase , Antioxidantes/farmacologia , Butirilcolinesterase , Inibidores Enzimáticos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
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