Enantioselective analysis of the pesticide imazamox after in vitro permeability study in Caco-2 cells.

Imazamox (IMX), a chiral herbicide used in cereals and oilseed crops to control weeds, is commonly sold as a racemic mixture. Its enantiomers, being chiral compounds, may exhibit unique properties when exposed to chiral environments. While IMX enantiomers have been reported to degrade differently in soil and be toxic to some species, their effects on human systems remain poorly understood.

Enantioselective in vitro metabolism of the herbicide diclofop-methyl: Prediction of toxicokinetic parameters and reaction phenotyping.

Human exposure to contaminants of emerging concern, like pesticides, has increased in the past decades. Diclofop-methyl (DFM) is a chiral herbicide that is employed as a racemic mixture (rac-DFM) in soybean and other crops against wild oats. Studies have shown that DFM has enantioselective action (higher for R-DFM), degradation (faster for S-DFM), and metabolism, producing diclofop (DF) which is also a pesticide.

Oxidation Products from the Neolignan Licarin A by Biomimetic Reactions and Assessment of in vivo Acute Toxicity.

Licarin A, a dihydrobenzofuranic neolignan presents in several medicinal plants and seeds of nutmeg, exhibits strong activity against protozoans responsible for Chagas disease and leishmaniasis. From biomimetic reactions by metalloporphyrin and Jacobsen catalysts, seven products were determined: four isomeric products yielded by epoxidation from licarin A, besides a new product yielded by a vicinal diol, a benzylic aldehyde, and an unsaturated aldehyde in the structure of the licarin A. The incubation with rat and human liver microsomes partially reproduced the biomimetic reactions by the production of the same epoxidized product of 343 [M + H].

Pharmacokinetic study of AmB-NP-GR: A new granule form with amphotericin B to treat leishmaniasis and fungal infections.

Amphotericin B (AmB) has been the gold standard to treat systemic fungal infections. The use of AmB is restricted to hospitals because it poses several risks, mainly risks related to its high nephrotoxicity. Given the importance of this drug in medicine, new therapeutics and AmB formulations with nanotechnological improvements are required and could bring many benefits to patients.

In vitro-in vivo correlation of the chiral pesticide prothioconazole after interaction with human CYP450 enzymes.

Growing human demand for food has culminated in increased use of pesticides worldwide. Prothioconazole (PTC), a profungicide, is bioactivated by metabolic PTC oxidation to prothioconazole-desthio (D-PTC). Here, the in vitro phase I metabolism of PTC to D-PTC in human liver microsomes and human CYP450 forms was studied.

In vitro enantioselective inhibition of the main human CYP450 enzymes involved in drug metabolism by the chiral pesticide tebuconazole.

Tebuconazole (TEB) is a chiral triazole fungicide worldwide employed to control plant pathogens and preserve wood. People can be exposed to TEB either through diet and occupational contamination. This work investigates the in vitro inhibitory potential of rac-TEB, S-(+)-TEB, and R-(-)-TEB over the main cytochrome P450 enzymes (CYP450) using human liver microsomes to predict TEB in vivo inhibition potential.

Enantioselective inhibition of human CYP2C19 by the chiral pesticide ethofumesate: Prediction of pesticide-drug interactions in humans.

Ethofumesate is a chiral herbicide that may display enantioselective behavior in humans. For this reason, the enantioselective potential of ethofumesate and its main metabolite ethofumesate-2-hydroxy to cause pesticide-drug interactions on cytochrome P450 forms (CYPs) has been evaluated by using human liver microsomes. Among the evaluated CYPs, CYP2C19 had its activity decreased by the ethofumesate racemic mixture (rac-ETO), (+)-ethofumesate ((+)-ETO), and (-)-ethofumesate ((-)-ETO).

An appraisal of experimental designs: Application to enantioselective capillary electromigration techniques.

Enantioresolution processes are vital tools for investigating the enantioselectivities of chiral compounds. An analyst resolves to optimize enantioresolution conditions once they are determined. Generally, optimization is conducted by a one-factor-at-a-time (OFAT) approach.

Risk assessment of the chiral pesticide fenamiphos in a human model: Cytochrome P450 phenotyping and inhibition studies.

Fenamiphos (FS) is a chiral organophosphate pesticide that is used to control nematodes in several crops. Enantioselective differences may be observed in FS activity, bioaccumulation, metabolism, and toxicity. Humans may be exposed to FS through occupational and chronic (food, water, and environmental) exposure.

A fast-multiclass method for the determination of 21 endocrine disruptors in human urine by using vortex-assisted dispersive liquid-liquid microextraction (VADLLME) and LC-MS/MS.

Simplicity, speed, and reduced cost are essential demands for routine analysis in human biomonitoring studies. Moreover, the availability of higher volumes of human specimens is becoming more restrictive due to ethical controls and to the costs associated with sample transportation and storage. Thus, analytical methods requiring much lower sample volumes associated with simultaneous detection capability (multiclass analysis) are with a very high claim.

Enantioselective in vitro metabolism and in vitro-in vivo correlation of the herbicide ethofumesate in a human model.

Ethofumesate (ETO) is a chiral herbicide that is marketed as a racemic mixture in the European Union and the United States. The growing consumption of pesticides in the world, along with their presence in water and food, has increased human exposure to these chemicals. Another issue concerning these compounds is that each enantiomer of a chiral pesticide may interact with biomolecules differently.

Prediction of seriniquinone-drug interactions by in vitro inhibition of human cytochrome P450 enzymes.

Seriniquinone is a secondary metabolite isolated from a rare marine bacterium of the genus Serinicoccus. This natural quinone is highlighted for its selective cytotoxic activity toward melanoma cancer cells, in which rapid metastatic properties are still a challenge for clinical treatment of malignant melanoma. The progress of seriniquinone as a promising bioactive molecule for drug development requires the assessment of its clinical interaction potential with other drugs.

Yangambin and Epi-yangambin Isomers: New Purification Method from Ocotea fasciculata and First Cytotoxic Aspects Focusing on In Vivo Safety.

presents yangambin (YAN) and its isomer epi-yangambin (EPI-YAN) as major lignans, which are employed as the plant markers for quality control purposes and as potential pharmacological compounds. However, a gap between the pure isomers and safety and efficacy protocols is faced by the scientific community. In this context, this work aimed to report (i) a new and advantageous purifying process in a semi-preparative scale for YAN and EPI-YAN isolation from , and (ii) an cytotoxicity study to estimate, for the first time, the LD values of the isolated epimers, as well as the influence of albumin concentration in cell culture medium.

In vitro inhibition of human CYP2D6 by the chiral pesticide fipronil and its metabolite fipronil sulfone: Prediction of pesticide-drug interactions.

Fipronil is a chiral insecticide employed worldwide in crops, control of public hygiene and control of veterinary pests. Humans can be exposed to fipronil through occupational, food, and environmental contamination. Therefore, the risk assessment of fipronil in humans is important to protect human health.

In vitro enantioselective study of the toxicokinetic effects of chiral fungicide tebuconazole in human liver microsomes.

Tebuconazole (TEB) is a chiral triazole fungicide that is globally marketed and used as a racemic mixture to control plant pathogens. Due to its use as a racemic mixture, TEB may exhibit enantioselective toxicokinetics toward nontarget organisms, including humans. Therefore, the in vitro enantioselective metabolism of TEB by cytochrome P450 enzymes (CYP450) was studied using human liver microsomes, and the in vivo toxicokinetic parameters were predicted.

Evaluation of the enantioselective in vitro metabolism of the chiral pesticide fipronil employing a human model: Risk assessment through in vitro-in vivo correlation and prediction of toxicokinetic parameters.

The chiral pesticide fipronil is employed as a racemic mixture to control pests. Although there are no enantioselective differences in the fipronil enantiomer activities toward target organisms, fipronil enantiomers may exhibit enantioselective differences in their bioaccumulation, toxicity, and metabolism toward non-target organisms, including humans. The present work aims to provide significant reliable enantioselective information concerning fipronil risk assessment in humans.

Characterization of Casearin X Metabolism by Rat and Human Liver Microsomes.

Casearin X (CAS X) is the major clerodane diterpene isolated from the leaves of and has been extensively studied due to its powerful cytotoxic activity at low concentrations. Promising results for antitumor action have also been described when CAS X was administered intraperitoneally in mice. Conversely, loss of activity was observed when orally administered.

Paenibacillus polymyxa Associated with the Stingless Bee Melipona scutellaris Produces Antimicrobial Compounds against Entomopathogens.

Social insects are frequently observed in symbiotic association with bacteria that produce antimicrobial natural products as a defense mechanism. There is a lack of studies on the microbiota associated with stingless bees and their antimicrobial compounds. To the best of our knowledge, this study is the first to report the isolation of Paenibacillus polymyxa ALLI-03-01 from the larval food of the stingless bee Melipona scutellaris.

A fast and simple air-assisted liquid-liquid microextraction procedure for the simultaneous determination of bisphenols, parabens, benzophenones, triclosan, and triclocarban in human urine by liquid chromatography-tandem mass spectrometry.

The increasing awareness and public concern with hazard exposure to endocrine-disrupting chemicals calls for methods capable to handle numerous samples in short analysis time. In this present study, a novel method combining air-assisted liquid-liquid microextraction and liquid chromatography coupled to mass spectrometry was developed and validated for the extraction, preconcentration, and determination of 7 bisphenols (bisphenol A, bisphenol S, bisphenol AP, bisphenol P, bisphenol F, bisphenol AF, bisphenol Z), 7 parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-paraben, methyl-protocatechuic acid, and ethyl-protocatechuic acid), 5 benzophenones (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-8, and 4-hydroxybenzophenone), and two antimicrobials (triclosan and triclocarban) in human urine samples. Type and volume of solvent, extraction time (cycles), pH sample, ionic strength, agitation, and needle dimensions were evaluated.

Drug-resistant epilepsy and topiramate: Plasma concentration and frequency of epileptic seizures.

Topiramate (TPM) is a second-generation antiepileptic drug (AED), acting on drug-resistant epilepsy. The aim of the study was to evaluate the influence of the dose, use of other AEDs on TPM plasma concentration (C ), and frequency of epileptic seizures. A cross-sectional analytical study was developed with patients aged 18-60 years, for diagnosis of drug-resistant epilepsy, using TPM in monotherapy or associated with other AEDs.

Metabolism studies of chiral pesticides: A critical review.

The consumption of pesticides worldwide has been growing in recent decades, and consequently the exposure of humans and other animals to them as well. However, even though it is known that chiral pesticides can behave stereoselectively, the knowledge about the risks to human health and the environment is scarce. Among the pesticides registered to date, approximately 30% have at least one center of asymmetry, and just 7% of them are currently marketed as a pure stereoisomer or as an enriched mixture of the active stereoisomer.

In Vitro Metabolism of Artepillin C by Rat and Human Liver Microsomes.

Artepillin C, a natural product present in the Brazilian green propolis, has several biological properties. Among these properties, the antitumor action of this product is noteworthy and makes it a promising drug candidate for the treatment of several types of cancer. This paper describes the metabolism of Artepillin C in rat and human liver microsomes.

Determination of Levetiracetam in Human Plasma by Dispersive Liquid-Liquid Microextraction Followed by Gas Chromatography-Mass Spectrometry.

Levetiracetam (LEV) is an antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes. The use of this drug has been increasing in clinical practice and intra- or -interindividual variability has been exhibited for special population. For this reason, bioanalytical methods are required for drug monitoring in biological matrices.

In Vitro Metabolism Evaluation of the Ergot Alkaloid Dihydroergotamine: Application of Microsomal and Biomimetic Oxidative Model.

Dihydroergotamine is a semisynthetic natural product derived from ergotamine, an ergot alkaloid. It is used to treat migraines, a neurological disease characterized by recurrent moderate to severe headaches. In this work, the metabolism of dihydroergotamine was evaluated in a biomimetic phase I reaction, aiming to verify all possible formed metabolites.

In-line coupling of an achiral-chiral column to investigate the enantioselective in vitro metabolism of the pesticide Fenamiphos by human liver microsomes.

The distinct activity and toxicity of enantiomers has increased concern about the use of chiral pesticides. The chiral pesticide Fenamiphos (FS) is employed as a racemic mixture to control nematode pests. Although recent studies revealed that FS enantiomers possess different toxicity, the toxicokinetics and liver metabolism of these enantiomers in humans remain unclear.