Toxicity of synthetic cathinones in human kidney (HK-2) cells

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Synergistic activity of a novel class of azoimidazole dyes with polyvinylpyrrolidone-silver nanoparticles for the development of antibacterial textiles

The high demand for novel antimicrobial textiles by the medical, health care, hygiene, sportswear, personal protective equipment, and filtration sectors promoted the growth of functional textiles. However, the efficacy of antimicrobial agents against different pathogens is a considerable challenge due to the distinctive mechanisms of action and resistance. The development of novel synergistic antimicrobial agents may offer numerous opportunities to enhance antimicrobial effectiveness, namely boost the activity of individual agents, reduce dosages, minimize toxicity, and amplify the activity spectrum. On the one hand, azo dyes containing a heterocycle present good tinctorial strength and brightness of shades. In particular, the imidazole ring also has interesting antimicrobial, analgesic, and anti-inflammatory properties. On the other hand, silver nanoparticles (AgNPs) are renowned antimicrobial agents against a wide range of microorganisms, but their application is limited by the toxicity observed for effective concentrations. In this work, a novel class of azoimidazoles (AzoIz) and corresponding precursors (AmIz) were conjugated with polyvinylpyrrolidone-coated AgNPs, and their synergistic effect was assessed against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results showed interesting antimicrobial properties of the novel AzoIz molecules when combined with a very small concentration of AgNPs. Thus, the application of these conjugates in textiles may lead to highly colored materials with remarkable antimicrobial properties, which worth to be further explored

Antimicrobial activity of a library of thioxanthones and their potential as efflux pump inhibitors

The overexpression of efflux pumps is one of the causes of multidrug resistance, which leads to the inefficacy of drugs. This plays a pivotal role in antimicrobial resistance, and the most notable pumps are the AcrAB-TolC system (AcrB belongs to the resistance-nodulation-division family) and the NorA, from the major facilitator superfamily. In bacteria, these structures can also favor virulence and adaptation mechanisms, such as quorum-sensing and the formation of biofilm. In this study, the design and synthesis of a library of thioxanthones as potential efflux pump inhib-itors are described. The thioxanthone derivatives were investigated for their antibacterial activity and inhibition of efflux pumps, biofilm formation, and quorum-sensing. The compounds were also studied for their potential to interact with P-glycoprotein (P-gp, ABCB1), an efflux pump present in mammalian cells, and for their cytotoxicity in both mouse fibroblasts and human Caco-2 cells. The results concerning the real-time ethidium bromide accumulation may suggest a potential bacterial efflux pump inhibition, which has not yet been reported for thioxanthones. Moreover, in vitro studies in human cells demonstrated a lack of cytotoxicity for concentrations up to 20 µM in Caco-2 cells, with some derivatives also showing potential for P-gp modulation.This research was supported by national funds through FCT (Foundation for Science and Technology) within the scope of UIDB/04423/2020, UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR), and under the project PTDC/SAU-PUB/28736/2017 (reference POCI-01–0145-FEDER-028736), co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF and by FCT through national funds and structured program of R&D&I ATLANTIDA (NORTE-01-0145-FEDER-000040), supported by NORTE2020, through ERDF, and CHIRALBIO ACTIVE-PI-3RL-IINFACTS-2019

Antifungal activity of a new derivative of 5-aminoimidazole-4-carbohydrazonamide

[Excerpt] Fungal infections, as recognized by the World Health Organization (WHO), are among the most worrying challenges for the medical community due to their high incidence, recurrence, and the emergence of resistance to the few available drugs and therapies. The discovery of new molecules with antifungal activity, exhibiting new mechanisms of action and less side effects, thus represents an important step forward in the development of alternative treatments [1]

Chiral Thioxanthones as Modulators of P-glycoprotein: Synthesis and Enantioselectivity Studies

Recently, thioxanthone derivatives were found to protect cells against toxic P-glycoprotein (P-gp) substrates, acting as potent inducers/activators of this efflux pump. The study of new P-gp chiral modulators produced from thioxanthone derivatives could clarify the enantioselectivity of this ABC transporter towards this new class of modulators. The aim of this study was to evaluate the P-gp modulatory ability of four enantiomeric pairs of new synthesized chiral aminated thioxanthones (ATxs) 1–8, studying the influence of the stereochemistry on P-gp induction/ activation in cultured Caco-2 cells. The data displayed that all the tested compounds (at 20 µM) significantly decreased the intracellular accumulation of a P-gp fluorescent substrate (rhodamine 123) when incubated simultaneously for 60 min, demonstrating an increased activity of the efflux, when compared to control cells. Additionally, all of them except ATx 3 (+), caused similar results when the accumulation of the P-gp fluorescent substrate was evaluated after pre-incubating cells with the test compounds for 24 h, significantly reducing the rhodamine 123 intracellular accumulation as a result of a significant increase in P-gp activity. However, ATx 2 (−) was the only derivative that, after 24 h of incubation, significantly increased P-gp expression. These results demonstrated a significantly increased P-gp activity, even without an increase in P-gp expression. Therefore, ATxs 1–8 were shown to behave as P-gp activators. Furthermore, no significant differences were detected in the activity of the protein when comparing the enantiomeric pairs. Nevertheless, ATx 2 (−) modulates P-gp expression differently from its enantiomer, ATx 1 (+). These results disclosed new activators and inducers of P-gp and highlight the existence of enantioselectivity in the induction mechanism. © 2018 by the authors.Acknowledgments: This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT—Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020, the project PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599—Promover a Produção Científica e Desenvolvimento Tecnológico e a Constituição de Redes Temáticas (3599-PPCDT)) as well as by the project INNOVMAR—Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, within Research Line NOVELMAR), supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The authors also thank Sara Cravo, Department of Chemistry, Laboratory of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Porto, for technical support in chiral HPLC. Renata Silva acknowledges Fundação para a Ciência e a Tecnologia (FCT) for her Post-doctoral grant (SFRH/BPD/110201/2015)

Pieris brassicae excrements: cytological effects

Attention has been focused on identifying naturally occurring compounds with anticarcinogenic activity. Epidemiological data evidence the protective role of Brassica species, especially due to their phenolics and glucosinolates. Pieris brassicae, an insect whose larvae constitutes a frequent pest of Brassica species, has the capacity to uptake, metabolize and excrete these phytochemicals by the faeces. Phenolics composition of excrements from P. brassicae reared on Brassica oleracea var. acephala presents flavonoids (sulfated and glycosilated), some of them not detected in host plant [1]. Their volatiles profile shows compounds belonging to different classes, with especial attention to terpenes and glucosinolates breakdown products (sulfur and nitrogen compounds) [2]. Furthermore, this matrix already revealed to have antioxidative properties [1]

Simultaneous determination of amphetamine derivatives in human urine after SPE extraction and HPLC-UV analysis

Amphetamine derivatives are a class of compounds increasingly abused as recreational drugs in various regions of the world. Although d-amphetamine (AMPH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are among the most commonly used, the abuse of other designer drugs such as 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and 4-methylthioamphetamine (4-MTA) and their involvement in acute intoxications has been increasingly reported. There is evidence that abusers ingest these compounds either alone or in combination and the respective monitoring is important for both legal and health care purposes in hospital emergency. In the present study a simple and clean solid-phase extraction procedure from urine of AMPH and MDMA, and their major metabolites p-hydroxyamphetamine (OH-AMPH) and methylenedioxyamphetamine (MDA) and 2C-B and 4-MTA was developed. Analysis was performed by HPLC-UV and the precision of the technique was between 2.9 and 5.3% for all compounds. For the overall procedure, the precision values were between 3.3 and 5.9%. Recoveries obtained from spiked urines at three concentration levels were better than 84 +/- 4% for the six compounds. The limit of detection of the method for the compounds (between 5.3 and 84.0 ng) enables their identification in urine after ingestion of fatal and non-fatal doses. The main advantages of the present method lie in its simple, clean and reliable SPE extraction method of the six amphetamine derivatives from urine followed by their simultaneous detection and quantification by liquid chromatography with UV detection.info:eu-repo/semantics/publishedVersio

Mephedrone

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