Synthetic Cathinones: Recent Developments, Enantioselectivity Studies and Enantioseparation Methods.

New psychoactive substances represent a public health threat since they are not controlled by international conventions, are easily accessible online and are sold as a legal alternative to illicit drugs. Among them, synthetic cathinones are widely abused due to their stimulant and hallucinogenic effects. To circumvent the law, new derivatives are clandestinely synthesized and, therefore, synthetic cathinones keep emerging on the drug market, with their chemical and toxicological properties still unknown. In this review, a literature assessment about synthetic cathinones is presented focusing on the recent developments, which include more than 50 derivatives since 2014. A summary of their toxicokinetic and toxicodynamic properties are also presented. Furthermore, synthetic cathinones are chiral compounds, meaning that they can exist as two enantiomeric forms which may present different biological and toxicological activities. To analyze the enantiomers, the development of enantiomeric resolution methods for synthetic cathinones is crucial. Many methods have been reported over the years that include mostly chromatographic and electromigration techniques, with liquid chromatography using chiral stationary phases being the technique of choice. This review intended to present an overview of enantioselectivity studies and enantioseparation analysis regarding synthetic cathinones, highlighting the relevance of chirality and current trends.

A Metabolomic Approach for the In Vivo Study of Gold Nanospheres and Nanostars after a Single-Dose Intravenous Administration to Wistar Rats.

Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and sensitive approaches such as metabolomics are much needed to discriminate toxicity, specially at low doses. The current work aims to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars (of similar ~40 nm diameter and coated with 11-mercaptoundecanoic acid) 24 h after an intravenous administration of a single dose (1.33 × 1011 AuNPs/kg) to Wistar rats. The biodistribution of both types of AuNPs was determined by graphite furnace atomic absorption spectroscopy. The metabolic effects of the AuNPs on their main target organ, the liver, were analyzed using a GC-MS-based metabolomic approach. Conventional toxicological endpoints, including the levels of ATP and reduced and oxidized glutathione, were also investigated. The results show that AuNPs preferentially accumulate in the liver and, to a lesser extent, in the spleen and lungs. In other organs (kidney, heart, brain), Au content was below the limit of quantification. Reduced glutathione levels increased for both nanospheres and nanostars in the liver, but ATP levels were unaltered. Multivariate analysis showed a good discrimination between the two types of AuNPs (sphere- versus star-shaped nanoparticles) and compared to control group. The metabolic pathways involved in the discrimination were associated with the metabolism of fatty acids, pyrimidine and purine, arachidonic acid, biotin, glycine and synthesis of amino acids. In conclusion, the biodistribution, toxicological, and metabolic profiles of gold nanospheres and gold nanostars were described. Metabolomics proved to be a very useful tool for the comparative study of different types of AuNPs and raised awareness about the pathways associated to their distinct biological effects.

Development and optimization of a HS-SPME-GC-MS methodology to quantify volatile carbonyl compounds in Port wines.

A method based on headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography-triple quadrupole/mass spectrometry detection (GC-TQ/MS) with a prior derivatization step with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) was developed to quantify carbonyl compounds in different categories of Port wines. Optimal extraction conditions were obtained incubating 2 ml of wine with 2.3 g/l of PFBHA for 10 min and extracted during 20 min at 32 °C. The method was validated for 38 carbonyl compounds (alkanals, alkenals, Strecker aldehydes, dialdehydes, ketones and furan aldehydes) with regard to linearity, repeatability, inter and intra-day precision and accuracy, showing that the method is suitable for the determination of carbonyl compounds in wines. Tawny wines with 'indication of age' (10-40 years old) presented the highest levels of some carbonyl compounds, such as propanal, pentanal, hexanal, Strecker aldehydes, diacetyl, methyl glyoxal, 3-pentanone and 2-furfural, whereas Ruby wines were characterized by the highest amounts of some unidentified compounds.

Metabolic and biological prospecting of Coreopsis tinctoria

Coreopsis tinctoria Nutt., Asteraceae, flowering tops infusion has been traditionally used in many countries to control hyperglycaemia. In this work we report for the first time fatty acids and volatile compounds in this species. Fifteen fatty acids and sixteen volatile compounds were determined by GC-ITMS, being saturated fatty acids and monoterpenes the main compounds. The antioxidant and antibacterial potential of this matrix was checked for the first time by several in vitro assays. A concentration-dependent activity was noticed against DPPH, nitric oxide and superoxide radicals. Antibacterial capacity was assessed against Gram-positive and Gram-negative bacteria, being more effective against the first. Additionally, acetylcholinesterase and butyrylcholinesterase inhibitory activity was also evaluated, but no effect was found. Our results provide evidence of a wide diversity of compounds with several biological properties, improving the knowledge on this poorly studied matrix, which can lead to an increment of the use of C. tinctoria flowering tops, namely in food and pharmaceutical applications.

Chemical composition and biological screening of Capsella bursa-pastoris

Capsella bursa-pastoris (L.) Medik. (Brassicaceae) is a wild herb with high nutritional value that can be eaten raw or cooked. A metabolomic study was performed with different extracts of its aerial parts that were tested concerning their antiradical, acetylcholinesterase inhibitory and antibacterial activities. Phenolic compounds were identified and quantified by HPLC-DAD, organic acids and amino acids were determined by HPLC-UV, while free fatty acids and sterols were analysed by GC-ITMS. The vegetal material was rich in kaempferol-3-O-rutinoside (mean value 2247.09 mg/kg of dry plant), quinic acid (95628.00 mg/kg of dry plant), arginine (mean value of 1.18 mg/kg of dry plant), palmitic acid (284.48 mg/kg) and β-sitosterol (28 percent). The extracts presented a concentration-dependent antiradical activity (against DPPH•, O2•- and LOO•), being most effective against •NO (EC25 0.20 µg/mL). In addition, the extracts were also acetylcholinesterase inhibitors and antibacterial active, revealing that, besides the plant's good nutritional value, it presents important biological properties as well.

In vitro studies to assess the antidiabetic, anti-cholinesterase and antioxidant potential of Spergularia rubra.

Spergularia rubra is distributed all over the world, being its infusion used as diuretic. In spite of its large use, the antidiabetic, anti-cholinesterase and antioxidant activities of this species have not been assessed and its chemical composition is scarcely known. In the work herein a hydromethanolic extract was studied. Thirty-six phenolic compounds were determined by HPLC-DAD, comprising non-acylated C-glycosyl flavones (38%), C-glycosyl flavones acylated with aromatic acids (36%), C-glycosyl flavones acylated with aliphatic acids (13%) and 10% corresponded to C-glycosyl flavones with a mixed acylation. Organic acids (oxalic, citric, malic, quinic and fumaric acids) and fatty acids (azelaic, myristic, palmitic, linoleic, linolenic and stearic acids) are described for the first time. Their determination by HPLC-UV and GC-IT-MS allowed finding concentrations of 192.15 and 34.87g/kg, respectively. The extract showed a dose-dependent response against DPPH, superoxide and nitric oxide radicals. The same effect was observed in the α-glucosidase inhibitory assay and against acetylcholinesterase and butyrylcholinesterases. The bioactivities observed may be due, at least partially, to the presence of the different metabolites determined in the present study. The results suggest that the dried extract of S. rubra may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia and inhibit cholinesterases, and or as food additive due to its antiradical activity.