Miconazole-like Scaffold is a Promising Lead for Naegleria fowleri-Specific CYP51 Inhibitors.

Developing drugs for brain infection by Naegleria fowleri is an unmet medical need. We used a combination of cheminformatics, target-, and phenotypic-based drug discovery methods to identify inhibitors that target an essential N. fowleri enzyme, sterol 14-demethylase (NfCYP51). A total of 124 compounds preselected in silico were tested against N. fowleri. Nine primary hits with EC50 ≤ 10 µM were phenotypically identified. Cocrystallization with NfCYP51 focused attention on one primary hit, miconazole-like compound 2a. The S-enantiomer of 2a produced a 1.74 Å cocrystal structure. A set of analogues was then synthesized and evaluated to confirm the superiority of the S-configuration over the R-configuration and the advantage of an ether linkage over an ester linkage. The two compounds, S-8b and S-9b, had an improved EC50 and KD compared to 2a. Importantly, both were readily taken up into the brain. The brain-to-plasma distribution coefficient of S-9b was 1.02 ± 0.12, suggesting further evaluation as a lead for primary amoebic meningoencephalitis.

Electrochemical Sensing Platform Based on Carbon Dots for the Simultaneous Determination of Theophylline and Caffeine in Tea.

A simple and selective method for the determination of caffeine (CAF) and theophylline (THEO) has been developed for a glassy carbon electrode (GCE) modified with a composite including carbon dots (CDs) and chitosan (CS). To our knowledge, there are no previous studies that analyze a CDs-modified GCE for the presence of CAF and THEO. The electrochemical behavior of a GCE modified with a CDs-CS composite was studied in acidic medium by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Considering the sensor analytical parameters, the same linear concentrations range was found for CAF and THEO ranging from 1 × 10-5 to 5 × 10-3 mol L-1 with the same detection limit (LOD) of 1 × 10-6 mol L-1. The reproducibility and repeatability data were satisfactory in terms of RSD%. Moreover, the storage stability was evaluated, evidencing good results whatever the experimental conditions used. The developed sensor was applied for the simultaneous determination of CAF and THEO in tea and drug, and results were compared with those obtained with HPLC-ESI-MS in SIR mode as an independent method optimized on purpose. The electrochemical sensor presents the undoubled advantages in terms of cheapness, portability, and ease of use, since it does not require skilled personnel.

Phytochemical Analysis and In Vitro Antileukemic Activity of Alkaloid-Enriched Extracts from Vinca sardoa (Stearn) Pignatti.

Vinca sardoa (Stearn) Pignatti, known as Sardinian periwinkle, is widely diffused in Sardinia (Italy). This species contains indole alkaloids, which are known to have a great variety of biological activities. This study investigated the antileukemic activity against a B lymphoblast cell line (SUP-B15) of V. sardoa alkaloid-rich extracts obtained from plants grown in Italy, in Iglesias (Sardinia) and Rome (Latium). All the extracts showed a good capacity to induce reductions in cell proliferation of up to 50% at the tested concentrations (1-15 µg/mL). Moreover, none of the extracts showed cytotoxicity on normal cells at all the studied concentrations.

Electrochemical Synthesis of Carbon Quantum Dots.

Carbon quantum dots (CDs) are "small" carbon nanostructures with excellent photoluminescence properties, together with low-toxicity, high biocompatibility, excellent dispersibility in water as well as organic solvents. Due to their characteristics, CDs have been studied for a plethora of applications as biosensors, luminescent probes for photodynamic and photothermal therapy, fluorescent inks and many more. Moreover, the possibility to obtain carbon dots from biomasses and/or organic waste has strongly promoted the interest in this class of carbon-based nanoparticles, having a promising impact in the view of circular economy and sustainable processes. Within this context, electrochemistry proved to be a green, practical, and efficient method for the synthesis of high-quality CDs, with the possibility to fine-tune their characteristics by changing operational parameters. This review outlines the principal and most recent advances in the electrochemical synthesis of CDs, focusing on the electrochemical set-up optimization.

Phytochemical Characterization of Malt Spent Grain by Tandem Mass Spectrometry also Coupled with Liquid Chromatography: Bioactive Compounds from Brewery By-Products.

BACKGROUND: Brewer's spent grain (BSG) is one of the main by-products of beer industry, little used because of its high moisture making it difficult to transport and store. Mainly used as animal feed and for energy production, the agro-industrial waste have recently attracted attention as source of bioactive compounds, with potential applications in many sectors as food, nutraceutical, pharmaceutical, cosmetic, food packaging. The present work focuses on BSG as potential source of valuable small-size bioactive compounds. METHODS: Laboratory-made BSG was obtained by using four base malts for mashing. After drying, BSG was eco-friendly extracted with water and the extracts analyzed by untargeted ElectroSpray Ionization (ESI)-Mass Spectrometry (MS)/Mass Spectrometry (MS) (ESI-MS/MS) infusion experiments and by targeted High Performance Liquid Chromatography-PhotoDiodeArray-ElectroSpray Ionization-Mass Spectrometry (HPLC-PDA-ESI-MS) in Selected Ion Recording (SIR) mode analysis, to investigate the metabolic profile, the phenolic profile, the individual phenolic content, and tryptophan content. Aqueous extracts of malts and wort samples were also analyzed for a comparison. Data were statistically analyzed by ANOVA test. An explorative analysis based on Principal Component Analysis (PCA) was also carried out on malts, wort and threshes, in order to study correlation among samples and between samples and variables. RESULTS: The untargeted ESI-MS/MS infusion experiments provided the mass spectral fingerprint of BSG, evidencing amino acids (γ-aminobutyric acid, proline, valine, threonine, leucine/isoleucine, lysine, histidine, phenylalanine and arginine) and organic and inorganic acids (pyruvic, lactic, phosphoric, valerianic, malonic, 2-furoic, malic, citric and gluconic acids), besides sugars. γ-Aminobutyric acid and lactic acid resulted predominant among the others. The targeted HPLC-PDA-ESI-MS in SIR mode analysis provided the phenolic profile of the polar fraction of BSG, evidenced tryptophan as the main residual metabolite in BSG (62.33-75.35 µg/g dry BSG), and catechin (1.13-4.24 µg/g dry BSG) as the representative phenolic antioxidant of not pre-treated BSG samples. The chemometric analysis of the individual compounds content in BSG, malt and wort evidenced similarities and differences among the samples. CONCLUSIONS: As main goal, the phytochemical characterization of BSG from base malts highlighted BSG as a potential source of small biomolecules, as tryptophan and catechin, besides γ-aminobutyric acid and lactic acid, opening to new perspectives of application for BSG. Strategies for their recovery are a future challenge. Moreover, ESI-MS/MS analysis was confirmed as a powerful tool for fast characterization of complex matrix. Last, results obtained by chemometric elaboration of data demonstrated the possibility to monitor a small number of molecules to ensure the quality of a final product.

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF3: the case of alkyne hydration. Chemistry vs electrochemistry.

In order to replace the expensive metal/ligand catalysts and classic toxic and volatile solvents, commonly used for the hydration of alkynes, the hydration reaction of alkynes was studied in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF4) adding boron trifluoride diethyl etherate (BF3·Et2O) as catalyst. Different ionic liquids were used, varying the cation or the anion, in order to identify the best one, in terms of both efficiency and reduced costs. The developed method was efficaciously applied to different alkynes, achieving the desired hydration products with good yields. The results obtained using a conventional approach (i.e., adding BF3·Et2O) were compared with those achieved using BF3 electrogenerated in BMIm-BF4, demonstrating the possibility of obtaining the products of alkyne hydration with analogous or improved yields, using less hazardous precursors to generate the reactive species in situ. In particular, for terminal arylalkynes, the electrochemical route proved to be advantageous, yielding preferentially the hydration products vs the aldol condensation products. Importantly, the ability to recycle the ionic liquid in subsequent reactions was successfully demonstrated.

Metabolic Profile of Agropyron repens (L.) P. Beauv. Rhizome Herbal Tea by HPLC-PDA-ESI-MS/MS Analysis.

Agropyron repens (L.) P. Beauv. (couch grass) is a world-wide infesting rhizomatous plant with pharmacological applications. Chemical research is focused on its allelopathic and anti-inflammatory components, which are mainly present in the essential oil. Conversely, the aqueous extracts have been sparingly investigated, although the herbal tea is by far the most used formulation. To fill the gap, the metabolic profile of Agropyron repens rhizome herbal tea was investigated by electrospray ionization (ESI) tandem-mass spectrometry (MS/MS); the phenolic profile was investigated by HPLC-PDA-ESI-MS/MS. ESI-MS fingerprinting was provided, evidencing diagnostic ions for saccharides, organic acids and amino acids. The HPLC-PDA-ESI-MS/MS analysis evidenced at least 20 characteristic phenolic compounds, the most representative being caffeoyl and feruloyl quinic esters, followed by coumaric, caffeic and ferulic acids, and hesperidin among flavonoids. In addition, the essential amino acid tryptophan was identified for the first time. The results suggest new perspectives of applications for Agropyron repens rhizome.

Electrochemical Bottom-Up Synthesis of Chiral Carbon Dots from L-Proline and Their Application as Nano-Organocatalysts in a Stereoselective Aldol Reaction.

Chirality is undoubtedly a fundamental property of nature since the different interactions of optically active molecules in a chiral environment are essential for numerous applications. Thus, in the field of asymmetric synthesis, the search for efficient, sustainable, cost-effective and recyclable chiral catalysts is still the main challenge in organic chemistry. The field of carbon dots (CDs) has experienced tremendous development in the last 15 years, including their applications as achiral catalysts. Thus, understanding the implications of chirality in CDs chemistry could be of utmost importance to achieving sustainable and biocompatible chiral nanocatalysts. An efficient and cost-effective electrochemical synthetic methodology for the synthesis of L-Proline-based chiral carbon dots (CCDs) and EtOH-derived L-Proline-based chiral carbon dots (CCDs) is herein reported. The electrochemical set-up and reaction conditions have been thoroughly optimised and their effects on CCDs size, photoluminescence, as well as catalytic activity have been investigated. The obtained CCDs have been successfully employed to catalyze an asymmetric aldol reaction, showing excellent results in terms of yield, diastereo- and enantioselectivity. Moreover, the sustainable nature of the CCDs was demonstrated by recycling the catalysts for up to 3 cycles without any loss of reactivity or stereoselectivity.

Targeted phenolic profile of radler beers by HPLC-ESI-MS/MS: the added value of hesperidin to beer antioxidants.

The well-known health beneficial properties of beer are mainly due to phenolic antioxidants. Citrus-flavored beers represent a growing side-market in the beer industry, sparingly investigated to date. The phenolic profile of commercial radler beers (R1, R2) was investigated to evaluate the impact of the lemon juice added to beer in the industrial production. Results were compared to those obtained for opportunely chosen commercial beer (B) and lemonade (L). The study was carried out by an HPLC-MS/MS with an electrospray ionization source in selected ion recording mode, analyzing in a single chromatographic run 26 compounds belonging to the different phenolic classes of hydroxybenzoic, hydroxycinnamic and caffeoylquinic acids, flavonoids and prenylflavonoids. Different phenolic profiles were found for R1 and R2, mainly ascribed to different malt/hop/recipe used for the beer. High to very high level of hesperidin were found in the radlers, so that a major impact on phenolic antioxidants of the radlers was due to the lemon. Similarly, a major impact of the lemon aromas was found, D-limonene being the dominant peak resulting from the GC-MS analysis of the volatile fraction of the radlers.

Design, Synthesis, and In Vitro, In Silico and In Cellulo Evaluation of New Pyrimidine and Pyridine Amide and Carbamate Derivatives as Multi-Functional Cholinesterase Inhibitors.

Alzheimer disease is an age-linked neurodegenerative disorder representing one of the greatest medical care challenges of our century. Several drugs are useful in ameliorating the symptoms, even if none could stop or reverse disease progression. The standard approach is represented by the cholinesterase inhibitors (ChEIs) that restore the levels of acetylcholine (ACh) by inhibiting the acetylcholinesterase (AChE). Still, their limited efficacy has prompted researchers to develop new ChEIs that could also reduce the oxidative stress by exhibiting antioxidant properties and by chelating the main metals involved in the disease. Recently, we developed some derivatives constituted by a 2-amino-pyrimidine or a 2-amino-pyridine moiety connected to various aromatic groups by a flexible amino-alkyl linker as new dual inhibitors of AChE and butyrylcholinesterase (BChE). Following our previous studies, in this work we explored the role of the flexible linker by replacing the amino group with an amide or a carbamic group. The most potent compounds showed higher selectivity against BChE in respect to AChE, proving also to possess a weak anti-aggregating activity toward Aß42 and tau and to be able to chelate Cu2+ and Fe3+ ions. Molecular docking and molecular dynamic studies proposed possible binding modes with the enzymes. It is noteworthy that these compounds were predicted as BBB-permeable and showed low cytotoxicity on the human brain cell line.

Free N-heterocyclic carbenes from Brønsted acidic ionic liquids: Direct detection by electrospray ionization mass spectrometry.

RATIONALE: The occurrence of N-heterocyclic carbenes in imidazolium-based ionic liquids has long been discussed, but no spectroscopic evidence has been reported yet due to their transient nature. The insertion of an ionizable acid group into the cation scaffold of an ionic liquid which acts as a charge tag allows for the direct detection of free carbenes by mass spectrometry. METHODS: Three different Brønsted acidic ionic liquids were synthesized: 1-methyl-3-carboxymethylimidazolium chloride (MAICl), 1-methyl-3-carboxymethylimidazolium acetate (MAIAc) and the corresponding 2-(3-methyl-1H-imidazol-3-ium-1-yl)acetate zwitterion (MAI - H). The speciation of these compounds was then analysed by electrospray ionization ion-trap mass spectrometry in the negative ion mode. RESULTS: The C2-H deprotonation of the imidazolium cation leading to the formation of the corresponding carbene is highly affected by the basic properties of the counter-anion. In the case of MAICl and MAI - H ionic liquids, no charged species corresponding to the free N-heterocyclic carbene was detected. On the contrary, in the presence of a sufficiently basic anion, such as acetate of MAIAc ionic liquid, an intense signal related to the free carbenic species was observed without the addition of an external base. CONCLUSIONS: In situ formation of free N-heterocyclic carbenes from Brønsted acidic ionic liquids was demonstrated, highlighting the crucial role of anion basicity in promoting the C2-H proton abstraction from imidazolium cations with a carboxylic side chain.

Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures.

Histoplasma capsulatum is a fungus that causes histoplasmosis. The increased evolution of microbial resistance and the adverse effects of current antifungals help new drugs to emerge. In this work, fifty-four nitrofurans and indoles were tested against the H. capsulatum EH-315 strain. Compounds with a minimum inhibitory concentration (MIC90) equal to or lower than 7.81 µg/mL were selected to evaluate their MIC90 on ATCC G217-B strain and their minimum fungicide concentration (MFC) on both strains. The quantification of membrane ergosterol, cell wall integrity, the production of reactive oxygen species, and the induction of death by necrosis-apoptosis was performed to investigate the mechanism of action of compounds 7, 11, and 32. These compounds could reduce the extracted sterol and induce necrotic cell death, similarly to itraconazole. Moreover, 7 and 11 damaged the cell wall, causing flaws in the contour (11), or changing the size and shape of the fungal cell wall (7). Furthermore, 7 and 32 induced reactive oxygen species (ROS) formation higher than 11 and control. Finally, the cytotoxicity was measured in two models of cell culture, i.e., monolayers (cells are flat) and a three-dimensional (3D) model, where they present a spheroidal conformation. Cytotoxicity assays in the 3D model showed a lower toxicity in the compounds than those performed on cell monolayers. Overall, these results suggest that derivatives of nitrofurans and indoles are promising compounds for the treatment of histoplasmosis.

Gold Nanomaterials-Based Electrochemical Sensors and Biosensors for Phenolic Antioxidants Detection: Recent Advances.

Antioxidants play a central role in the development and production of food, cosmetics, and pharmaceuticals, to reduce oxidative processes in the human body. Among them, phenolic antioxidants are considered even more efficient than other antioxidants. They are divided into natural and synthetic. The natural antioxidants are generally found in plants and their synthetic counterparts are generally added as preventing agents of lipid oxidation during the processing and storage of fats, oils, and lipid-containing foods: All of them can exhibit different effects on human health, which are not always beneficial. Because of their relevant bioactivity and importance in several sectors, such as agro-food, pharmaceutical, and cosmetic, it is crucial to have fast and reliable analysis Rmethods available. In this review, different examples of gold nanomaterial-based electrochemical (bio)sensors used for the rapid and selective detection of phenolic compounds are analyzed and discussed, evidencing the important role of gold nanomaterials, and including systems with or without specific recognition elements, such as biomolecules, enzymes, etc. Moreover, a selection of gold nanomaterials involved in the designing of this kind of (bio)sensor is reported and critically analyzed. Finally, advantages, limitations, and potentialities for practical applications of gold nanomaterial-based electrochemical (bio)sensors for detecting phenolic antioxidants are discussed.

Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives.

Fungal diseases affect more than 1 billion people worldwide. The constant global changes, the advent of new pandemics, and chronic diseases favor the diffusion of fungal pathogens such as Candida, Cryptococcus, Aspergillus, Trichophyton, Histoplasma capsulatum, and Paracoccidioides brasiliensis. In this work, a series of nitrofuran derivatives were synthesized and tested against different fungal species; most of them showed inhibitory activity, fungicide, and fungistatic profile. The minimal inhibitory concentration (MIC90) values for the most potent compounds range from 0.48 µg/mL against H. capsulatum (compound 11) and P. brasiliensis (compounds 3 and 9) to 0.98 µg/mL against Trichophyton rubrum and T. mentagrophytes (compounds 8, 9, 12, 13 and 8, 12, 13, respectively), and 3.9 µg/mL against Candida and Cryptococcus neoformans strains (compounds 1 and 5, respectively). In addition, all compounds showed low toxicity when tested in vitro on lung cell lines (A549 and MRC-5) and in vivo in Caenorhabditis elegans larvae. Many of them showed high selectivity index values. Thus, these studied nitrofuran derivatives proved to be potent against different fungal species, characterized by low toxicity and high selectivity; for these reasons, they may become promising compounds for the treatment of mycoses.

Recent Advances in Imidazolium-Based Dicationic Ionic Liquids as Organocatalysts: A Mini-Review.

Imidazolium-based dicationic ionic liquids (DILs) are gaining considerable space in the field of organocatalysis mainly due to the opportunities in offering new possible applicable structural variations. In addition to the well-known variables which made the ionic liquids (ILs) famous as the type of cation and anion used, the nature of the molecular spacer moiety turns out a further possibility to improve some physicochemical properties, for example, solubility, acidity, electrochemical behavior, and so on. For this reason, this class of ionic liquids has been considered as possible competitors to their corresponding monocationic salts in replacing common catalysts in organic synthesis, particularly in cases in which their bidentate nature could positively affect the catalytic activity. This mini-review is intended to highlight the progress carried out in the last six years in the field of organocatalysis, including DILs as such and as hybrids with polymers, nanomaterials, and composites.

Salmonella Typhimurium and Pseudomonas aeruginosa Respond Differently to the Fe Chelator Deferiprone and to Some Novel Deferiprone Derivatives.

The ability to obtain Fe is critical for pathogens to multiply in their host. For this reason, there is significant interest in the identification of compounds that might interfere with Fe management in bacteria. Here we have tested the response of two Gram-negative pathogens, Salmonella enterica serovar Typhimurium (STM) and Pseudomonas aeruginosa (PAO1), to deferiprone (DFP), a chelating agent already in use for the treatment of thalassemia, and to some DFP derivatives designed to increase its lipophilicity. Our results indicate that DFP effectively inhibits the growth of PAO1, but not STM. Similarly, Fe-dependent genes of the two microorganisms respond differently to this agent. DFP is, however, capable of inhibiting an STM strain unable to synthesize enterochelin, while its effect on PAO1 is not related to the capability to produce siderophores. Using a fluorescent derivative of DFP we have shown that this chelator can penetrate very quickly into PAO1, but not into STM, suggesting that a selective receptor exists in Pseudomonas. Some of the tested derivatives have shown a greater ability to interfere with Fe homeostasis in STM compared to DFP, whereas most, although not all, were less active than DFP against PAO1, possibly due to interference of the added chemical tails with the receptor-mediated recognition process. The results reported in this work indicate that DFP can have different effects on distinct microorganisms, but that it is possible to obtain derivatives with a broader antimicrobial action.

New Pyrimidine and Pyridine Derivatives as Multitarget Cholinesterase Inhibitors: Design, Synthesis, and In Vitro and In Cellulo Evaluation.

A new series of pyrimidine and pyridine diamines was designed as dual binding site inhibitors of cholinesterases (ChEs), characterized by two small aromatic moieties separated by a diaminoalkyl flexible linker. Many compounds are mixed or uncompetitive acetylcholinesterase (AChE) and/or butyrylcholinesterase (BChE) nanomolar inhibitors, with compound 9 being the most active on Electrophorus electricus AChE (EeAChE) (Ki = 0.312 µM) and compound 22 on equine BChE (eqBChE) (Ki = 0.099 µM). Molecular docking and molecular dynamic studies confirmed the interaction mode of our compounds with the enzymatic active site. UV-vis spectroscopic studies showed that these compounds can form complexes with Cu2+ and Fe3+ and that compounds 18, 20, and 30 have antioxidant properties. Interestingly, some compounds were also able to reduce Aß42 and tau aggregation, with compound 28 being the most potent (22.3 and 17.0% inhibition at 100 µM on Aß42 and tau, respectively). Moreover, the most active compounds showed low cytotoxicity on a human brain cell line and they were predicted as BBB-permeable.

In Situ Anodically Oxidized BMIm-BF4: A Safe and Recyclable BF3 Source.

The anodic oxidation of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF4) efficiently generates BF3 from BF4-. This Lewis acid, strongly bound to the ionic liquids, can be efficiently used in classical BF3-catalyzed reactions. We demonstrated the BF3/BMIm-BF4 reactivity in four reactions, namely, a domino Friedel-Crafts/lactonization of phenols, the Povarov reaction, the Friedel-Crafts benzylation of anisole, and the multicomponent synthesis of tetrahydro-11H-benzo[a]xanthen-11-ones. In comparison with literature data using BF3-Et2O in organic solvents, in all the presented cases, analogous or improved results were obtained. Moreover, the noteworthy advantages of the developed method are the in situ generation of BF3 (no storing necessity) in the required amount, using only the electron as redox reagent, and the recycling of BMIm-BF4 for multiple subsequent runs.

Design, synthesis and biological evaluation of a series of iron and copper chelating deferiprone derivatives as new agents active against Candida albicans.

Candida albicans, in specific conditions, is responsible of severe invasive systemic candidiasis that are related to its ability to produce biofilm on biological and artificial surfaces. Many studies reported the role of iron in fungal growth and virulence and the ability of metal chelating agents to interfere with C. albicans metabolism, virulence and biofilm formation. Here we report the activity of 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone (deferiprone) derivatives against C. albicans planktonic cells and biofilm. Some of the studied compounds (2b and 3b) were able to chelate Fe(III) and Cu(II), and showed an interesting activity on planktonic cells (MIC50 of 32 µg/mL and 16 µg/mL respectively) and on biofilm formation (BMIC50 of 32 µg/mL and 16 µg/mL respectively) in cultured ATCC 10,231C. albicans; this activity was reduced, in a concentration dependent way, by the addition of Fe(III) and Cu(II) to the culture media. Furthermore, the most active compound 3b showed a low toxicity on Galleria mellonella larvae.

Impact of Dealcoholization by Osmotic Distillation on Metabolic Profile, Phenolic Content, and Antioxidant Capacity of Low Alcoholic Craft Beers with Different Malt Compositions.

Beer antioxidants originate mainly from malts, classified as colored, caramel, and roasted, according to the malting process. This study aimed to characterize, in terms of phenolic antioxidants, three types of Pale Ale craft beers brewed using increasing percentage of dark malt (0, 5, and 15% Caraamber malt, called PA100, PA95, PA85, respectively) and to evaluate the impact of dealcoholization by osmotic distillation (OD) on the same antioxidants. All the alcoholic (PA, 6.2-6.8 vol %) and low alcoholic (LA-PA, 1 vol %) beers were analyzed by HPLC-ESI-MS/MS, total phenolic content (TPC), and antioxidant activity (AA): similar phenolic profiles were evidenced and 43 compounds identified or tentatively identified. Some differences were found among PA100, PA95, and PA85: PA85 was richer in free phenolic compounds (10.55 mg/L) and had a higher TPC (463.7 GAE mg/L) and AA (852.1 TE mg/L). LA-PA beers showed the same phenolic profile and similar TPC and AA compared to PA beers; however, there were some differences regarding LA-PA85 (5.91 mg/L). Dealcoholization by OD seemed to weakly affect the phenolic fraction. ESI-MS/MS infusion experiments evidenced oligosaccharides, small organic acids, and amino acids, whose presence was confirmed and quantitated by NMR: besides ethanol and other alcohols, weak to strong loss of low-molecular-weight metabolites was evidenced in LA-PA beers.