Chiral analysis of pesticides and drugs of environmental concern: biodegradation and enantiomeric fraction

The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF). The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.info:eu-repo/semantics/publishedVersio

Enantiomeric separation of tramadol and Its metabolites: method validation and application to environmental samples

The accurate assessment of racemic pharmaceuticals requires enantioselective analytical methods. This study presents the development and validation of an enantioselective liquid chromatography with a fluorescence detection method for the concomitant quantification of the enantiomers of tramadol and their metabolites, N-desmethyltramadol and O-desmethyltramadol, in wastewater samples. Optimized conditions were achieved using a Lux Cellulose-4 column 150 × 4.6 mm, 3 µm isocratic elution, and 0.1% diethylamine in hexane and ethanol (96:4, v/v) at 0.7 mL min−1. The samples were extracted using 150 mg Oasis® mixed-mode cation exchange (MCX) cartridges. The method was validated using a synthetic effluent of a laboratory-scale aerobic granular sludge sequencing batch reactor. The method demonstrated to be selective, accurate, and linear (r2 > 0.99) over the range of 56 ng L−1 to 392 ng L−1. The detection and the quantification limits of each enantiomer were 8 ng L−1 and 28 ng L−1 for tramadol and N-desmethyltramadol, and 20 ng L−1 and 56 ng L−1 for O-desmethyltramadol. The feasibility of the method was demonstrated in a screening study in influent and effluent samples from a wastewater treatment plant. The results demonstrated the occurrence of tramadol enantiomers up to 325.1 ng L−1 and 357.9 ng L−1, in the effluent and influent samples, respectively. Both metabolites were detected in influents and effluentsinfo:eu-repo/semantics/publishedVersio

Aqueous extracts of fish roe as a source of several bioactive compounds

Regular consumption of seafood and, in particular, fish has been associated with important health benefits. A fish product that has been increasingly included in the human nutrition is roe. Despite its nutritional value has been established (fatty acid profile and protein content), the knowledge of the composition of its aqueous extracts is still limited. This work describes the bioactive compounds profile in the roe-derived aqueous extracts of three different marine species (sardine, horse mackerel and sea bass) using a method based on liquid chromatography coupled to high-resolution mass spectrometry with an electrospray ionisation source (LC-ESI/HRMS). The presence of substances with well-known nutritional and functional properties (e.g., antioxidant and anti-inflammatory properties) was demonstrated, namely essential amino acids (e.g., taurine), peptides (e.g., anserine and carnosine), B-group vitamins (e.g., nicotinamide) and gadusol. Therefore, roe-derived aqueous extracts are excellent sources of bioactive compounds and may be used as a font of functional components for several medical and veterinary applications.This research was funded by FCT/MCTES and FSE/POCH, grant numbers PD/169/2013, PD/BD/113795/2015, PTDC/CTM-BIO/4388/2014, and the NORTE 2020 Structured Project within the R&D&I Structured Project, co-funded by Norte2020—Programa Operacional Regional do Norte, grant number NORTE-01-0145-FEDER-000021 and national funds by FCT through the projects UIDB/04423/2020 and UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry— CIIMAR) and ERDF, through the COMPETE-POFC program in the framework of the program PT2020

Influence of PDLA nanoparticles size on drug release and interaction with cells

Polymeric nanoparticles (NPs) are strong candidates for the development of systemic and targeted drug delivery applications. Their size is a determinant property since it defines the NP–cell interactions, drug loading capacity, and release kinetics. Herein, poly(D,L-lactic acid) (PDLA) NPs were produced by the nanoprecipitationmethod, in which the influence of type and concentration of surfactant as well as PDLA concentration were assessed. The adjustment of these parameters allowed the successful production of NPs with defined medium sizes, ranging from 80 to 460 nm. The surface charge of the different NPs populations was consistently negative. Prednisolone was effectively entrapped and released from NPs with statistically different medium sizes (i.e., 80 or 120 nm). Release profiles indicate that these systems were able to deliver appropriate amounts of drug with potential applicability in the treatment of inflammatory conditions. Both NPs populations were cytocompatible with human endothelial and fibroblastic cells, in the range of concentrations tested (0.187–0.784 mg/mL). However, confocal microscopy revealed that within the range of sizes tested in our experiments, NPs presenting amedium size of 120 nmwere able to be internalized in endothelial cells. In summary, this study demonstrates the optimization of the processing conditions to obtain PDLA NPs with narrow size ranges, and with promising performance for the treatment of inflammatory diseases.info:eu-repo/semantics/publishedVersio

Toxicity of the 3,4-methylenedioxymethamphetamine and its enantiomers to Daphnia magna after isolation by semipreparative chromatography

MDMA (3,4-methylenedioxymethamphetamine) is a chiral psychoactive recreational drug sold in illicit markets as racemate. Studies on the impact of MDMA on aquatic organisms are scarce. While enantioselectivity in toxicity in animals and humans has been reported, none is reported on aquatic organisms. This study aimed to investigate the ecotoxicological effects of MDMA and its enantiomers in Daphnia magna. For that, enantiomers (enantiomeric purity > 97%) were separated by liquid chromatography using a homemade semipreparative chiral column. Daphnids were exposed to three concentrations of (R,S)-MDMA (0.1, 1.0 and 10.0 µg L−1) and two concentrations of (R)- and (S)-enantiomers (0.1 and 1.0 µg L−1) over the course of 8 days. Morphophysiological responses were dependent on the substance form and daphnia development stage, and they were overall not affected by the (R)-enantiomer. Changes in swimming behaviour were observed for both the racemate and its enantiomers, but enantioselective effects were not observed. Reproductive or biochemical changes were not observed for enantiomers whereas a significant decrease in acetylcholinesterase and catalase activity was noted at the highest concentration of (R,S)-MDMA (10 µg L−1). Overall, this study showed that sub-chronic exposure to MDMA racemate and its enantiomers can interfere with morphophysiological and swimming behaviour of D. magna. In general, the (R)-enantiomer demonstrated less toxicity than the (S)-enantiomer.This work was financially supported by national funds through the FCT/MCTES (PIDDAC), under the project PTDC/CTA-AMB/6686/2020, and partially supported through the projects UIDB/04423/2020 and UIDP/04423/2020 (Group of Natural Products and Medicinal ChemistryCIIMAR)

On the bioactivity of Echinacea purpurea extracts to modulate the production of inflammatory mediators

Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography–high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-α, interleukin -IL-1β, and IL-6), and to generate ROS/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.This research was funded by the Fundação para a Ciência e a Tecnologia (FCT) to the PhD grant of SFV (PD/BD/135246/2017 and COVID/BD/152012/2021) and the projects PATH (PD/00169/2013), FROnTHERA (NORTE-01-0145-FEDER-000023), Cells4_IDs (PTDC/BTM-SAL/28882/2017), and the NORTE 2020 Structured Project, co-funded by Norte2020 (NORTE-01-0145-FEDER-000021). This research was also partially supported by national funds by FCT through the projects UIDB/04423/2020 and UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR) and ERDF, through the COMPETE—POFC program in the framework of the program PT2020

Echinacea purpurea fractions represent promising plant-based anti-inflammatory formulations

Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the extracts were fractionated into phenol/carboxylic acid (F1) and alkylamide fraction (F2). The chemical fingerprint of bioactive compounds in the fractions was evaluated by LC-HRMS. E. purpurea extracts and fractions significantly reduced pro-inflammatory cytokines (interleukin 6 and/or tumor necrosis factor) and reactive oxygen and nitrogen species (ROS/RNS) production by lipopolysaccharide-stimulated primary human monocyte-derived macrophages. Dichloromethanolic extract obtained from roots (DE-R) demonstrated the strongest anti-inflammatory activity. Moreover, fractions exhibited greater anti-inflammatory activity than whole extract. Indeed, alkylamides must be the main compounds responsible for the anti-inflammatory activity of extracts; thus, the fractions presenting high content of these compounds presented greater bioactivity. It was demonstrated that alkylamides exert their anti-inflammatory activity through the downregulation of the phosphorylation of p38, ERK 1/2, STAT 3, and/or NF-κB signaling pathways, and/or downregulation of cyclooxygenase 2 expression. E. purpurea extracts and fractions, mainly DE-R-F2, are promising and powerful plant-based anti-inflammatory formulations that can be further used as a basis for the treatment of inflammatory diseases.This work was financially supported by the FCT to the Ph.D. grants of S.F.V. (PD/BD/135246/2017 and COVID/BD/152012/2021), S.M.G. (SFRH/BD/136814/2018), and C.C. (CEECIND/04058/2018), and the projects PATH (PD/00169/2013), HEALTH-UNORTE (NORTE-01- 0145-FEDER-000039) and the NORTE 2020 Structured Project, co-funded by Norte2020 (NORTE-01- 0145-FEDER-000021

Enantioselective Synthesis, Enantiomeric Separations and Chiral Recognition

Chirality is a geometric property associated with the asymmetry of tridimensional features that accompanies our daily life at macroscopic as well as microscopic molecular levels [...