Synthesis and Anti-Chikungunya Virus (CHIKV) Activity of Novel 1,4-Naphthoquinone Sulfonamide and Sulfonate Ester Derivatives

Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae family. Since its first description in 1952, the disease has spread worldwide, affecting populations in both tropical and temperate countries. To date, there is no licensed vaccine or specific pharmacological treatment. Therefore, there is an increasing urgency in developing new antiviral drugs capable of specifically inhibiting viral replication. In the present work, we report the synthesis and antiviral activity evaluation of nineteen naphthoquinone derivatives, containing a sulfonamide or sulfonate group. Cell viability assays indicated a low toxic potential for all tested compounds and inhibitory assays against CHIKV identified five compounds with potent activity. The compounds were also evaluated for their virucidal potential, and the results demonstrated that compound 11a exhibited a virucidal effect higher than 70% in the treatment with 20 µM. Furthermore, in silico studies were performed to predict the antiviral drug targets.

Multifunctional activity of graphene oxide-based nanoformulation against the disease vector, Aedes aegypti

Aedes aegypti management is a global concern due to the absence of medication and effective vaccines. The pesticide-mediated health hazards and rising insecticide resistance in mosquitoes have aggravated the issues. As graphene Oxide (GO)- based nanoformulations are considered a novel mosquito management strategy; the present investigation evaluated the efficacy of GO-based nanoformulations conjugated with malathion (ML) and endosulphan (EN) against Ae. aegypti. The GO was synthesised by Hummers’ method and was confirmed by UV-visible spectral analysis. The GO-ML and GO-EN binary mixtures (1:1 and 1:2) were assayed for toxic potential against mosquito larvae as per WHO protocol and the dead larvae were scrutinized for morphological deformations/abnormalities. The contact irritancy potential of GO nanoformulations was also evaluated against adult Ae. aegypti. The UV-visible spectrum of GO showed a narrow and high peak at ~300 nm corresponding to an n-π* plasmon peak. The GO-insecticide binary mixtures augmented the ML and EN toxicity by 80.43% and 6.43-fold, respectively. The GO-ML mixture-exposed larvae revealed cuticular deposition of black soot while larvae exposed to GO-EN exhibited disintegrated gut viscera. GO-insecticide combinations increased flights in Ae. aegypti denoting irritant potential. The effectual toxic, abrasive and irritant activity of GO-insecticide nanoformulations recommends developing graphene-based toxicants for mosquito management

Etazene induces developmental toxicity in vivo Danio rerio and in silico studies of new synthetic opioid derivative

Synthetic opioids are gaining more and more popularity among recreational users as well as regular abusers. One of such novel psychoactive substance, is etazene, which is the most popular opioid drug in the darknet market nowadays. Due to limited information available concerning its activity, we aimed to characterize its developmental toxicity, including cardiotoxicity with the use of in vivo Danio rerio and in silico tools. Moreover, we aimed, for the first time, to characterize the metabolite of etazene, which could become a potential marker of its use for future forensic analysis. The results of our study proved severe dose-dependent developmental toxicity of etazene (applied concentrations 10–300 µM), including an increase in mortality, developmental malformations, and serious cardiotoxic effects, as compared with well-known and used opioid—morphine (applied concentrations 1–50 mM). In silico findings indicate the high toxic potential of etazene which may lead to drug-drug interactions and accumulation of substances. Furthermore, phase I metabolite of etazene resulting from N-dealkylation reaction was identified, and therefore it should be considered as a target for toxicological screening. Nonetheless, the exact mechanism of observed effects in response to etazene should be further examined.

Biodegradation of Linear Alkylbenzene sulfonate-Anthracene Mixture by a Microbial Consortium isolated from Sediment

Linear alkylbenzene sulfonate and anthracene are chemical compounds which form pollutant mixtures with high toxic potential, causing damage to ecosystems. The process known as biodegradation is an effective, low-cost process carried out by microbial populations that reduces the toxic effect of linear alkylbenzene sulfonate and anthracene. In the present study, biodegradation was determined at different concentrations of linear alkylbenzene sulfonate, anthracene and the mixture of both compounds. The resulting reduction in toxicity produced by the mixture, the compounds separately and their biodegradation intermediaries was assessed using a microbial model. The ISO 9439 system was used to assess the biodegradation effect of a microbial consortium isolated from polluted sediment on 5, 10 and 20 mg/l of linear alkylbenzene sulfonate and the same concentrations of anthracene. Toxicity was determined by measuring inhibition of Bacillus cereus dehydrogenase activity produced by 0.25 ml aliquots of the linear alkylbenzene sulfonate, anthracene and the mixture of both compounds before and after they had been subjected to the biodegradation test. After 11 days, the linear alkylbenzene sulfonate -anthracene mixture was biodegraded to a greater degree than the compounds individually (3057.36 μmol CO2), but at a concentration of 20 mg/l of both compounds, a marked inhibition of biodegradation was observed. A reduction in toxicity produced by the biodegradation of linear alkylbenzene sulfonate and its mixture with anthracene at 5 and 10 mg/l respectively was observed.

Effect of Early Life Exposure of Polystyrene Microplastics on Behavior and DNA Methylation in Later Life Stage of Zebrafish

Microplastic contamination has received increasing attention in recent years, and concern regarding the toxicity of microplastics to the environment and humans has increased. In this study, we investigated the neurodevelopmental toxicity of polystyrene microplastics (PSMPs) in the zebrafish Danio rerio under different exposure scenario. We investigated the effect of early life exposure to PSMPs on responses later in life, under different exposure scenarios. Zebrafish were exposed to PSMPs during embrionic stage, then allowed the fish to recover. The neurodevelopmental toxic responses were investigated using fish behavior and behavior-related gene expression. Early life exposure to PSMPs did not alter fish behavior at the early stage, however, it led to hyperactivity later life-stage. Generally, oxidative stress (i.e. sod2 and nrf2a) and nervous system (i.e. slc6a4b, npy and nrbf2)-related gene expression increased in all PSMPs-exposed fish. DNA hypomethylation was observed in fish challenged for a second time using the same PSMPs. Taken together, the current results imply that PSMPs have neurodevelopmental toxic potential when introduced early in life.

Hepatic and renal cellular cytotoxic effects of heparin-coated superparamagnetic Iron oxide nanoparticles

Background Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used in several biomedical engineering in vivo. Although various surface modifications have been made to these non-biodegradable nanoparticles to make them more biocompatible, their toxic potential still remains a major concern. Method In this study, we newly developed unfractionated heparin (UFH)-coated and low molecular weight heparin (LMWH)-coated SPIO nanoparticles through surface modification engineering, which was compared with commercially available dextran-coated SPIO nanoparticles. Their toxicity such as cytotoxicity, single cell gel electrophoresis (SCGE) comet assay, intracellular reactive oxygen species (ROS) content and cellular apoptosis was evaluated to hepatic HepG2 and renal HK-2 cells. Results When UFH-, LMWH- or dextran-coated SPIO nanoparticles were applied, they did not affect the viability of HepG2 cell. However, HK-2 cells were more sensitive to dextran-coated SPIO nanoparticles than others. In genotoxicity assay using SCGE comet, DNA tail moment values in the groups treated with dextran- and LMWH-coated SPIO nanoparticles significantly increased. However, UFH-coated SPIO nanoparticles was only significantly lowing DNA tail moment value. In addition, UFH-coated SPIO nanoparticles had lower cytotoxicity in HepG2 and HK-2 cells compared to dextran-coated SPIO nanoparticles, especially in terms of apoptosis and intracellular ROS production. Conclusions Collectively, it is possible that UFH- coated SPIO nanoparticles can be used as alternative negative contrast agents.

Green process in benzoic acid derivatives synthesis/ Processo verde em síntese de derivados de ácido benzoico

Employing a methodology that meets various requirements of "Green Chemistry", the substances quinazolinyl benzoate (P1) and N-4-imidazolphenylbenzamide (P2) were synthesized through benzoylation reactions by the classical Schotten-Baumann method, in an aqueous environment and room temperature. The products were purified by recrystallization and characterized by melting point, thin layer chromatography (TLC) and infrared spectroscopy. Qualitative antioxidant activities with the diphenylpicrylhydrazyl radical (DPPH) and toxic potential against Artemia salina Leach larvae were also investigated. Only P2 indicated significant antioxidant activity. According to the medium lethal concentration values (LC50), used for P1 and P2, the toxic potential revealed, respectively, to be moderate for P1 and weak for P2. Despite the low yield obtained for the synthesis of P1, the characterizations indicate success in the preparations, within a synthetic strategy of low cost, efficient and ecologically sustainable.

Adsorption of methylene blue dye by different methods of obtaining shrimp residue chitin

The textile industry, very important for the world economy, generates an effluent containing dyes, and which, when discarded in water bodies without proper treatment, can cause impacts to human health and the environment. One of these widely used dyes is methylene blue, whose characteristics are high solubility in water and its toxic potential, and which effects range from eye irritations, nausea, vomiting and even mental confusion. Among the potential adsorbents of this dye is chitin, which is a biopolymer extracted from the shrimp exoskeleton. Aiming at the development of a low-cost adsorbent material with potential use in the textile effluent treatment industry, the ability to remove methylene blue dye by shrimp residue chitin, obtained by eleven different methodologies, was verified. The three most efficient treatments reached approximately 75% of dye removal, proving the high adsorption power of shrimp residue. In addition to providing technological development of materials, the research brings socioeconomic benefits to the fishermen’s colony with the use of shrimp residue for the adsorption of other waste from the textile industry, contributing to the sustainability of both activities and reducing the environmental impact.

Ochratoxin A induces behavioral and neurochemical changes in adult zebrafish

Ochratoxin A (OTA) is a mycotoxin produced by species of filamentous fungi widely found as a contaminant in food and with high toxic potential. Studies have shown that this toxin cause kidney and liver damage, however, data on the effects of exposure to OTA on the central nervous system are still scarce. Zebrafish (Danio rerio) is a teleost often used in translational research due to its physiological, genetic, and behavioral homology with mammals, in addition to being useful as an environmental bioindicator. Thus, this study aimed to investigate the effects of exposure to OTA on behavioral and neurochemical parameters in adult zebrafish. The animals were treated with different doses of OTA (1.38, 2.77, and 5.53 mg/kg) and submitted to behavioral evaluations in the open tank and social interaction tests. Subsequently, they were euthanized, and the brains were used to assess markers associated with oxidative status. In the open tank test OTA induced changes in distance, absolute turn angle, mean speed, and time-freezing. However, no significant effects were observed in the social interaction test. Moreover, OTA also induced alterations in neurochemical parameters with changes in non-protein thiols (NPSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). This study showed that OTA can affect neurobiological aspects in zebrafish even at low doses.