Chemical Strategies for Dendritic Magneto-plasmonic Nanostructures Applied to Surface-Enhanced Raman Spectroscopy

Chemical analyses in the field using surface-enhanced Raman scattering (SERS) protocols are expected to be part of several analytical procedures applied to water quality monitoring. To date, these endeavors have been supported by developments in SERS substrate nanofabrication, instrumentation portability, and the internet of things. Here, we report distinct chemical strategies for preparing magneto-plasmonic (Fe₃O₄ : Au) colloids, which are relevant in the context of trace-level detection of water contaminants due to their inherent multifunctionality. The main objective of this research is to investigate the role of poly(amidoamine) dendrimers (PAMAMs) in the preparation of SERS substrates integrating both functionalities into single nanostructures. Three chemical routes were investigated to design magneto-plasmonic nanostructures that translate into different ways for assessing SERS detection by using distinct interfaces. Hence, a series of magneto-plasmonic colloids have been characterized and then assessed for their SERS activity by using a model pesticide (thiram) dissolved in aqueous samples.     

Antiprotozoal and Antibacterial Activity of Ravenelin,a Xanthone Isolated from the Endophytic Fungus Exserohilum rostratum

The natural compound ravenelin was isolated from the biomass extracts of Exserohilum rostratum fungus, and its antimicrobial, antiplasmodial, and trypanocidal activities were evaluated. Ravenelin was isolated by column chromatography and HPLC and identified by NMR and MS. The susceptibility of Gram-positive and Gram-negative bacteria strains to ravenelin was determined by microbroth dilution assay. Cytotoxicity was evaluated in hepatocarcinoma cells (HepG2) and BALB/c peritoneal macrophages by using MTT. SYBR Green I-based assay was used in the asexual stages of Plasmodium falciparum. Trypanocidal activity was tested against the epimastigote and intracellular amastigote forms of Trypanosoma cruzi. Ravenelin was active against Gram-positive bacteria strains, with emphasis on Bacillus subtilis (MIC value of 7.5 µM). Ravenelin’s antiparasitic activities were assessed against both the epimastigote (IC₅₀ value of 5 ± 1 µM) and the intracellular amastigote forms of T. cruzi (IC₅₀ value of 9 ± 2 µM), as well as against P. falciparum (IC₅₀ value of 3.4 ± 0.4 µM). Ravenelin showed low cytotoxic effects on both HepG2 (CC₅₀ > 50 µM) and peritoneal macrophage (CC₅₀ = 185 ± 1 µM) cells with attractive selectivity for the parasites (SI values > 15). These findings indicate that ravenelin is a natural compound with both antibacterial and antiparasitic activities, and considerable selectivity indexes. Therefore, ravenelin is an attractive candidate for hit-to-lead development.     

Tacrines as Therapeutic Agents for Alzheimer's Disease. V. Recent Developments

Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non‐hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.     

An Insight into Kiwiberry Leaf Valorization: Phenolic Composition,Bioactivity and Health Benefits

During kiwiberry production, different by-products are generated, including leaves that are removed to increase the fruit’s solar exposure. The aim of this work was to extract bioactive compounds from kiwiberry leaf by employing microwave-assisted extraction (MAE). Compatible food solvents (water and ethanol) were employed. The alcoholic extract contained the highest phenolic and flavonoid contents (629.48 mg of gallic acid equivalents (GAE) per gram of plant material on dry weight (dw) (GAE/g dw) and 136.81 mg of catechin equivalents per gram of plant material on dw (CAE/g dw), respectively). Oppositely, the hydroalcoholic extract achieved the highest antioxidant activity and scavenging activity against reactive oxygen and nitrogen species (IC₅₀ = 29.10 μg/mL for O₂^•−, IC₅₀ = 1.87 μg/mL for HOCl and IC₅₀ = 1.18 μg/mL for ^•NO). The phenolic profile showed the presence of caffeoylquinic acids, proanthocyanidin, and quercetin in all samples. However, caffeoylquinic acids and quercetin were detected in higher amounts in the alcoholic extract, while proanthocyanidins were prevalent in the hydroalcoholic extract. No adverse effects were observed on Caco-2 viability, while the highest concentration (1000 µg/mL) of hydroalcoholic and alcoholic extracts conducted to a decrease of HT29-MTX viability. These results highlight the MAE potentialities to extract bioactive compounds from kiwiberry leaf.     

Metabolomics Insights of the Immunomodulatory Activities of Phlorizin and Phloretin on Human THP-1 Macrophages

Dihydrochalcones, phlorizin (PZ) and its aglycone phloretin (PT), have evidenced immunomodulatory effects through several mechanisms. However, the differential metabolic signatures that lead to these properties are largely unknown. Since macrophages play an important role in the immune response, our study aimed to characterise human THP-1 macrophages under PZ and PT exposure. A multiplatform-based untargeted metabolomics approach was used to reveal metabolites associated with the anti-inflammatory mechanisms triggered by the dihydrochalcones in LPS-stimulated macrophages, for the first time. Results showed differential phenotypic response in macrophages for all treatments. Dihydrochalcone treatment in LPS-stimulated macrophages mimics the response under normal conditions, suggesting inhibition of LPS response. Antagonistic effects of dihydrochalcones against LPS was mainly observed in glycerophospholipid and sphingolipid metabolism besides promoting amino acid biosynthesis. Moreover, PT showed greater metabolic activity than PZ. Overall, the findings of this study yielded knowledge about the mechanisms of action PZ and PT at metabolic level in modulating inflammatory response in human cells.     

Gouy wave modes: undistorted pulse focalization in a dispersive medium

Gouy wave modes are linear waves with finite energy that propagate without distortion at any phase and group velocity through a focal region in a dispersive medium. These features make them potentially useful for the onset and control of nonlinear interactions.     

Heterocyclic compounds as antiviral drugs: Synthesis,structure–activity relationship and traditional applications

A virus outbreak challenges the economic, medical, and public health infrastructure worldwide. More than one virus capable of triggering diseases have been identified per year since 1972, which requires the development of new ways of treatment and prevention, however, such processes are not rapid and easy. With the pandemic scenario experienced since early 2020, several drugs with well-known purposes have gained prominence, due to speculation of their use in the treatment against the new coronavirus. Among the main drugs studied, the vast majority contain a heterocyclic structure. In this review, we presented the traditional and efficient synthesis of 15 drugs that have been studied for the COVID-19 treatment, containing in their structure heterocycles like indole, quinoline, pyrimidone, tetrahydrofuran, pyrrolidine, triazole, pyridazine, pyrazole, pyrrolopyrimidine, azetidine, pyrrolotriazine, pyrazine, tetrahydropyran, benzofuran, spiroketal, and thiazole. Furthermore, we have shown the original applications, as well as their structure–activity relationship and what is their situation as a drug candidate against COVID-19. Thus, the objective was to consolidate the main synthetic and pharmacological aspects involving clinically developed heterocycles that at some point were presented as promising against SARS-CoV-2.     

Antiplasmodial Drugs in the Gas Phase: A CID and DFT Study of Quinolon-4(1H)-Imine Derivatives

The gas-phase behavior of 12 quinolon-4(1H)-imine derivatives with antiplasmodial activity was investigated using electrospray ionization tandem mass spectrometry together with collision induced dissociation and density functional theory (DFT) calculations. The most probable protonation site was predicted by calculating the proton affinity (PA) values for each possible protonation site and it was found to be the imine nitrogen for all compounds under study. Fragmentation pathways of the protonated molecules were proposed and the assignment of product ion structures was performed taking into account theoretical calculations. The nature of the quinoline substituent was found to influence the gas-phase behavior of the compounds under study. The data acquired allowed to bracket the proton affinity of the quinolin-4-imine scaffold, which can be a useful starting point to choose appropriate references for determining PA values of this scaffold. Figure

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Desorption/ionization efficiencies of triacylglycerols and phospholipids via EASI‐MS

Knowledge of the major effects governing desorption/ionization efficiency is required for the development and application of ambient mass spectrometry. Although all triacylglycerols (TAG) have the same favorable protonation and cationization sites, their desorption/ionization efficiencies can vary dramatically during easy ambient sonic‐spray ionization because of structural differences in the carbon chain. To quantify this somewhat surprising and drastic effect, we have performed a systematic investigation of desorption/ionization efficiencies as a function of unsaturation and length for TAG as well as for diacylglycerols, monoacylglycerols and several phospholipids (PL). Affinities for Na⁺ as a function of unsaturation level have also been assayed via comprehensive metadynamics calculations to understand the influence of this phenomenon on the ionization efficiency. The results suggest that dipole–dipole interactions within a carbon chain tuned by unsaturation sites govern ionization efficiency of TAG and PL. Copyright © 2014 John Wiley & Sons, Ltd.