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Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC50 values in the nanomolar range and AGR-2 being the most potent (IC50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis.

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BACKGROUND: Cholinesterase is a biomarker for poisonings by anticholinesterase agents, but its reference values are scarce, and possible interaction with collars containing parasiticides has not been studied. OBJECTIVES: We aimed to evaluate the serum cholinesterase activity of healthy dogs without a history of contact with anticholinesterase agents and healthy animals exposed to commercial collars containing organophosphate. METHODS: Ninety-nine dogs were used and included healthy animals without recent exposure to anticholinesterase agents and healthy animals previously exposed to diazinon collars. Serum quantification of the enzyme butyrylcholinesterase (BuchE) through spectrophotometry was conducted on all samples. In experiment 1, BuchE activity was quantified at time 0 and 7 days after, a time when the samples were kept at -18°C. In experiment 2, sampling times were 0, 7, 14, 21, 28, and 56 days. RESULTS: Time 0 values were 4622.38 ± 1311.53 U/L. After 7 days, a significant decay was observed, with a mean of 3934.45 ± 1430.45 U/L. Spearman's test was performed, finding a weak correlation between ALT, creatinine, total plasma proteins, age, weight, red blood cells, platelets, leukocytes, and BuchE activities. In experiment 2, the mean at time 0 was 4753 ± 454.8 U/L. With exposure to the collar, there was a decay of up to 93% after 14 days. CONCLUSIONS: Normality values of serum BuchE in healthy dogs without a history of exposure to anticholinesterase agents were 4360.8-4883.96 U/L. Freezing serum caused a decrease in BuchE activity. Exposure to commercial collars containing diazinon also reduced BuchE activity without clinical signs, indicating that previously exposed animals should be evaluated carefully.

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The effect of ethyl-4-bromophenyl carbamate on different Rhipicephalus microplus stages implanted in cattle was evaluated using the pen test with infestation chambers. Twelve steers were distributed into four groups (n = 3), each with four chambers (12 chambers per group), where approximately 1,000 R. microplus larvae were placed in each chamber. The chambers of the first group were sprayed with a solution of ethyl-4-bromophenyl carbamate (0.668 mg/mL) on day 2 post-infestation (PI) (exposed larvae). The chambers of the second group were sprayed with the same solution on day 8 PI (exposed nymphs), and the chambers of the third group were sprayed on day 16 PI (exposed adults) with the same solution. The chambers of the fourth group were used as controls. The percentages of engorged females, egg laying, egg production and egg hatching were evaluated in all groups. The percentage of cumulative reduction of hatched larvae was 98.3, 96.1 and 94.4% when larvae, nymph and adult stages were treated, respectively. The average cumulative reduction of hatched larvae, considering the three treated stages, was 96.3%, whereby the reproductive potential of this tick was drastically reduced. In conclusion, ethyl-4-bromophenyl carbamate acted as an ixodicide (lethal effect) when larval stages were sprayed and as a growth regulator when nymphal and adult stages were sprayed. The sum of these effects had a direct impact on the efficacy of the product in the pen test, and future studies will indicate the potential use of this product for tick control.

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INTRODUCTION: The human exposure to anticholinergic pesticides has been associated with the development of various diseases. Therefore, several biomarkers have been proposed for biomonitoring human exposure to anticholinergic pesticides. OBJECTIVE: This work evaluated the effect of human exposure to anticholinergic pesticides on ß-glucuronidase (GUSB) levels. METHODS: A systematic review was performed using PubMed, Web of Science, Scopus, and EBSCO databases up to December 2021. The statistical analysis employed standardized mean differences and meta-regression. And the trial sequential analysis was performed. RESULTS: Nine studies were included. A monotonic relationship was observed between poisoning severity and GUSB. Furthermore, BuChE levels were correlated with GUSB levels. CONCLUSIONS: The results indicated that GUSB levels could be used as a possible diagnosis biomarker in poisoning related to anticholinergic pesticide exposure. However, the use of GUSB to assess the chronic exposure to anticholinergic pesticides could be only performed in recent exposure (≈ 7 days after last exposure).

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Alzheimer's disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.

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The present study highlights a novel and advantageous protocol for accessing carbamates through the well-established three-component coupling reaction involving CO2 , amines, and alkyl halides. By employing an immobilized organic base, operating under mild reaction conditions, an array of alkyl carbamates in yields of up to 95 % could be isolated. This approach offers a broad and versatile product scope, allowing for the facile modification of both the amine and alkyl halide reactants. Notably, the pioneering use of an immobilized organic base, specifically the polymer-supported 1,8-diazabicyclo[5.4.0]undec-7-ene (PS-DBU), in this three-component reaction eliminates the need for classical purification steps, streamlining the process. To ensure practicality and sustainability, extensive studies were conducted to verify the recovery and reusability of the polymer-supported DBU catalyst, which consistently maintained the high chemical yield of the carbamates across multiple cycles. Overall, this innovative protocol represents a significant advancement in carbamate synthesis, combining efficiency, generality, and the potential for DBU recycling.

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Pesticides are a suitable tool for controlling plagues and disease vectors. However, their inappropriate use allows for contamination of the environment, soil, water, and foods. Carbamates and dithiocarbamates pesticides present accumulative effects in the human body resulting in hormonal, neurological and reproductive disorders, and some are still suspected or proven to give carcinogenic or mutagenic effects. This review provides a current electroanalytical approach in the carbamates and dithiocarbamates determination, showing the use of voltammetric techniques such as amperometry, cyclic and linear scan, differential pulse, and square wave voltammetry, indicating their advantages, disadvantages, and perspectives in electroanalytical detection of carbamates and dithiocarbamates in natural water and foods. Also are reported the different materials used in the preparation of working electrodes since their choice has an important impact on the success of the analytical applications, resulting in suitable sensitivity, selectivity, stability, and robustness.

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Compounds containing carbamate moieties and their derivatives can generate serious public health threats and environmental problems due their high potential toxicity. In this study, a quantitative structure-toxicity relationship (QSTR) model has been developed by using one hundred seventy-eight carbamate derivatives whose toxicities in rats (oral administration) have been evaluated. The QSRT model was rigorously validated by using either tested or untested compounds falling within the applicability domain of the model. A structure-based evaluation by docking from a series of carbamates with acetylcholinesterase (AChE) was carried out. The toxicity of carbamates was predicted using physicochemical, structural, and quantum molecular descriptors employing a DFT approach. A statistical treatment was developed; the QSRT model showed a determination coefficient (R2) and a leave-one-out coefficient (Q2LOO) of 0.6584 and 0.6289, respectively.

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Pesticides are chemical substances used to control, prevent, or destroy agricultural, domestic, and livestock pests. These compounds produce adverse changes in health, and they have been associated with the development of multiple chronic diseases. This study aimed to present a detailed review of the effect of pesticides on the oral cavity and the oral microbiome. In the oral cavity, pesticides alter and/or modify tissues and the microbiome, thereby triggering imbalance in the ecosystem, generating an inflammatory response, and activating hydrolytic enzymes. In particular, the imbalance in the oral microbiome creates a dysbiosis that modifies the number, composition, and/or functions of the constituent microorganisms and the local response of the host. Pesticide exposure alters epithelial cells, and oral microbiota, and disrupts the homeostasis of the oral environment. The presence of pesticides in the oral cavity predisposes the appearance of pathologies such as caries, periodontal diseases, oral cancer, and odontogenic infections. In this study, we analyzed the effect of organochlorines, organophosphates, pyrethroids, carbamates, bipyridyls, and triazineson oral cavity health and ecosystems.

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Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.

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