Molecules

22 pages, 1859 KB

Open AccessPerspective

A Perspective Towards More Sustainable Production of Biotechnologically Relevant Enzymes Using DESs

by Hugo Monteiro, Liane Meneses, Alexandre Paiva, Nuno Galamba and Ana Rita C. Duarte

Molecules 2025, 30(19), 3915; https://doi.org/10.3390/molecules30193915 (registering DOI) - 28 Sep 2025

The production of enzymes by the biotechnology industry yields high-value products for various sectors, including the pharmaceutical, food, textile, and detergent industries. Although enzymatic production processes are well established, there is a limitation with the purification of intracellular enzymes. These enzymes require extensive [...] Read more.

The production of enzymes by the biotechnology industry yields high-value products for various sectors, including the pharmaceutical, food, textile, and detergent industries. Although enzymatic production processes are well established, there is a limitation with the purification of intracellular enzymes. These enzymes require extensive downstream separation and purification processes, adding significant labor and costs compared to extracellular enzymes, which are easier to purify. In this work, we conducted a literature review to demonstrate that deep eutectic solvents (DESs) can be a viable alternative, especially as a more sustainable medium for enzyme stabilization and reactions. Additionally, we hypothesize about their potential to extract intracellular enzymes from microorganisms without disrupting their normal functions. Therefore, beyond the current state of the art, we offer a new perspective on a novel approach for producing intracellular enzymes more sustainably and efficiently. Full article

(This article belongs to the Section Molecular Liquids)

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16 pages, 1556 KB

Open AccessArticle

Tiliroside Suppresses Uric Acid Production in Hepatocytes and Attenuates Purine-Induced Hyperuricemia in Male ICR Mice

by Shin-ichi Adachi, Shinji Kondo, Yusuke Sato, Fumiaki Yoshizawa and Kazumi Yagasaki

Molecules 2025, 30(19), 3914; https://doi.org/10.3390/molecules30193914 (registering DOI) - 28 Sep 2025

Abstract

Tiliroside (kaempferol-3-O-(6′′-p-coumaroyl)-glucoside), a flavonoid glycoside found in rose hips and berries, has been reported to possess various bioactivities. This study aimed to evaluate its antihyperuricemic potential by assessing direct xanthine oxidase (XO) inhibitory activity, suppression of uric acid (UA) production in AML12 hepatocytes, [...] Read more.

Tiliroside (kaempferol-3-O-(6′′-p-coumaroyl)-glucoside), a flavonoid glycoside found in rose hips and berries, has been reported to possess various bioactivities. This study aimed to evaluate its antihyperuricemic potential by assessing direct xanthine oxidase (XO) inhibitory activity, suppression of uric acid (UA) production in AML12 hepatocytes, and efficacy in male ICR mice with purine nucleotide-induced hyperuricemia. XO inhibition was evaluated using a UV absorbance-based assay, and UA production was measured in hepatocytes stimulated with UA precursors. Mice were orally administered tiliroside for three days prior to purine nucleotide injection. Although tiliroside exhibited weak XO inhibition (IC₅₀ > 100 µM), it significantly suppressed UA production in hepatocytes in a concentration-dependent manner. In hyperuricemic mice, tiliroside (300 mg/kg) lowered plasma and hepatic UA levels by approximately 30% and 55%, respectively (p < 0.05). Hepatic XO activity was significantly decreased, while XO protein expression remained unchanged. Furthermore, mRNA levels of urate transporter 1 (URAT1) were significantly decreased in the kidney of tiliroside-treated hyperuricemic mice. These findings suggest that tiliroside exerts antihyperuricemic effects by suppressing UA production in the liver and modulating renal UA reabsorption. Tiliroside may serve as a beneficial dietary compound with bioactivity for the prevention and management of hyperuricemia and gout. Full article

(This article belongs to the Special Issue Bioactivity of Natural Compounds: From Plants to Humans)

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14 pages, 978 KB

Open AccessArticle

In Silico and RP HPLC Studies of Biologically Active 1,3,4-Thiadiazol-2-yl)-benzene-1,3-diols

by Marek Studziński, Katarzyna Barańska, Beata Paw, Bogusław Senczyna, Tadeusz Paszko and Joanna Matysiak

Molecules 2025, 30(19), 3913; https://doi.org/10.3390/molecules30193913 (registering DOI) - 28 Sep 2025

Abstract

Biologically active compounds from the 1,3,4-thiadiazol-2-yl)-benzene-1,3-diols group described earlier have been studied. Various approaches were used to determine their lipophilicity and predict pharmacokinetic properties. The lipophilicity parameters log k_w were determined using isocratic column chromatography and various stationary phases. Based on the [...] Read more.

Biologically active compounds from the 1,3,4-thiadiazol-2-yl)-benzene-1,3-diols group described earlier have been studied. Various approaches were used to determine their lipophilicity and predict pharmacokinetic properties. The lipophilicity parameters log k_w were determined using isocratic column chromatography and various stationary phases. Based on the standard curve and retention measurements by using an octadecyl column, the log D_7.4 distribution coefficient was determined. A weak correlation was found between the experimentally determined log k_w parameters and the in silico calculated log P descriptors. It was shown that the compounds partially exist in an ionized anionic form at physiological pH. The determined log D_7.4 parameter indicates that most of them have lipophilic character at the level recommended for potential drugs. Full article

(This article belongs to the Special Issue In Silico Methods Applied in Drug and Pesticide Discovery, 3rd Edition)

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45 pages, 2132 KB

Open AccessReview

A Comprehensive Review of Substitutional Silicon-Doped C₆₀ Fullerenes and Their Endohedral/Exohedral Complexes: Synthetic Strategies and Molecular Modeling Approaches

by Monika Zielińska-Pisklak, Patrycja Siekacz, Zuzanna Stokłosa and Łukasz Szeleszczuk

Molecules 2025, 30(19), 3912; https://doi.org/10.3390/molecules30193912 (registering DOI) - 28 Sep 2025

Abstract

Silicon-doped C₆₀ fullerenes represent a distinctive class of heterofullerenes with tunable structural, electronic, and chemical properties arising from substitutional incorporation of Si atoms into the carbon cage. This review provides a comprehensive analysis of substitutional Si–C₆₀ systems and their endohedral and [...] Read more.

Silicon-doped C₆₀ fullerenes represent a distinctive class of heterofullerenes with tunable structural, electronic, and chemical properties arising from substitutional incorporation of Si atoms into the carbon cage. This review provides a comprehensive analysis of substitutional Si–C₆₀ systems and their endohedral and exohedral complexes, with emphasis on synthesis strategies, structural features, and theoretical investigations. Experimental methods, including laser vaporization and arc discharge of Si-containing graphite targets, have enabled the preparation of Si-doped fullerenes, although challenges remain in controlling the dopant number, position, and distribution. Computational studies, dominated by density functional theory and molecular dynamics simulations, elucidate the effects of Si substitution on cage geometry, HOMO–LUMO modulation, charge localization, aromaticity, and finite-temperature stability. Exohedral functionalization and endohedral encapsulation of Si-doped cages significantly enhance their potential for applications in sensing, catalysis, energy storage, and nanomedicine. Si incorporation consistently strengthens adsorption of small molecules, pharmaceuticals, biomolecules, and environmental pollutants, often transforming weak physisorption into strong chemisorption with pronounced electronic and spectroscopic changes. The synergistic insights from experimental and theoretical work establish Si-doped fullerenes as versatile, electronically responsive nanoplatforms, offering a balance between stability, tunability, and reactivity, and highlighting future opportunities for targeted synthesis and application-specific design. Full article

(This article belongs to the Special Issue Crystal and Molecular Structure: Theory and Application)

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43 pages, 6760 KB

Open AccessReview

Efficient Approaches to the Design of Six-Membered Polyazocyclic Compounds—Part 2: Nonaromatic Frameworks

by Yuliya Yu. Titova, Elena A. Gyrgenova and Andrey V. Ivanov

Molecules 2025, 30(19), 3911; https://doi.org/10.3390/molecules30193911 (registering DOI) - 28 Sep 2025

Abstract

This review summarizes and compares literature data on the main strategies for the synthesis of saturated and/or partially saturated analogs of six-membered polyazoaromatic heterocycles. With a few exceptions, this data was published within the last 15–20 years. These strategies include, first of all, [...] Read more.

This review summarizes and compares literature data on the main strategies for the synthesis of saturated and/or partially saturated analogs of six-membered polyazoaromatic heterocycles. With a few exceptions, this data was published within the last 15–20 years. These strategies include, first of all, hydrogenation, which can be carried out in a classical manner (i.e., in the presence of a catalyst and molecular hydrogen) or via hydrogen transfer techniques. Other approaches comprise saturation of aromatic frameworks, which can be achieved using compounds other than hydrogen, such as hydroboration and dearomatic binding, or the creation of saturated or partially saturated polyazo heterocycles through the coupling of two or more molecules. Each of the above strategies has certain advantages and serious shortcomings and limitations. Despite the apparent methodological difficulties, it is demonstrated that the described approaches can sometimes give impressive results, including the production of optically pure products under relatively mild conditions. Full article

(This article belongs to the Section Organic Chemistry)

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34 pages, 4240 KB

Open AccessReview

Progress and Challenges in the Electrocatalytic Reduction of Nitrate to Ammonia

by Shupeng Yin and Yinglong Wang

Molecules 2025, 30(19), 3910; https://doi.org/10.3390/molecules30193910 (registering DOI) - 28 Sep 2025

Abstract

The escalating problem of nitrate pollution, coupled with the environmental burden of the Haber−Bosch process, has spurred intense interest in the electrocatalytic nitrate reduction reaction (eNO₃RR) as a sustainable route for simultaneous wastewater treatment and ammonia production. However, the efficiency and [...] Read more.

The escalating problem of nitrate pollution, coupled with the environmental burden of the Haber−Bosch process, has spurred intense interest in the electrocatalytic nitrate reduction reaction (eNO₃RR) as a sustainable route for simultaneous wastewater treatment and ammonia production. However, the efficiency and selectivity of eNO₃RR are hampered by the multi−step proton−coupled electron transfer process and the competing hydrogen evolution reaction. This review provides a comprehensive and critical overview of recent advances in understanding and designing catalysts for eNO₃RR. We begin by elucidating the fundamental mechanisms and key reaction pathways, followed by a discussion on how critical parameters (e.g., electrolyte microenvironment, applied potential, reactor design) dictate performance. Further discussion of recent advances in catalysts, including single−metal catalysts, alloy catalysts, transition metal compounds, single−atom catalysts, carbon−based non−metal catalysts, and composite catalysts, highlights their significant roles in enhancing both the efficiency and selectivity. A distinctive feature of this review is its consistent critical assessment of catalysts through the dual lenses of practicality and sustainable development. Finally, we outline prevailing challenges and propose future research directions aimed at developing scalable and commercially viable electrocatalytic systems for green nitrogen management. Full article

22 pages, 5059 KB

Open AccessArticle

Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer: Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery

by Adán Arizmendi-Izazaga, Napoleón Navarro-Tito, Gabriela Elizabeth Campos-Viguri, Hilda Jiménez-Wences, Macdiel Emilio Acevedo-Quiroz, Eric Genaro Salmerón-Bárcenas, Berenice Illades-Aguiar, Marco Antonio Leyva-Vázquez and Julio Ortiz-Ortiz

Molecules 2025, 30(19), 3909; https://doi.org/10.3390/molecules30193909 (registering DOI) - 28 Sep 2025

Abstract

Cervical cancer (CC) represents a major public health concern, ranking as the fourth most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among middle-aged women worldwide. CC is caused by persistent infection with high-risk human papillomaviruses (HR-HPVs), with HPV [...] Read more.

Cervical cancer (CC) represents a major public health concern, ranking as the fourth most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among middle-aged women worldwide. CC is caused by persistent infection with high-risk human papillomaviruses (HR-HPVs), with HPV 16 being the cause of more than 50% of CC cases. In this study, the exometabolome of the HPV 16-positive cell lines SiHa and Ca Ski, as well as the HPV 16-negative control cell line C-33 A, was evaluated. The exometabolome was validated through molecular signatures using a transcriptomic approach to identify genes encoding cellular metabolic enzymes. The exometabolome was analyzed using ¹H nuclear magnetic resonance spectroscopy (¹H-NMR). Exometabolomic profiles were subsequently compared through both multivariate and univariate statistical analyses to identify significant differences between cell lines. Molecular signatures were analyzed from the GSE9750 dataset obtained from the GEO database. Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan. An expression analysis showed increased expression of enzymes involved in amino acid synthesis, the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, galactose metabolism, and HIF-1α. These data suggest metabolites and metabolism-associated genes that can be used as non-invasive, stable diagnostic and prognostic biomarkers, as well as therapeutic targets for CC in the presence of HPV 16. Full article

(This article belongs to the Special Issue Novel Metabolism-Related Biomarkers in Cancer)

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26 pages, 1412 KB

Open AccessArticle

Multi-Step Synthesis of Chimeric Nutlin–DCA Compounds Targeting Dual Pathways for Treatment of Cancer

by Davide Illuminati, Rebecca Foschi, Paolo Marchetti, Vinicio Zanirato, Anna Fantinati, Claudio Trapella, Rebecca Voltan and Virginia Cristofori

Molecules 2025, 30(19), 3908; https://doi.org/10.3390/molecules30193908 (registering DOI) - 28 Sep 2025

Abstract

Chimeric compounds represent a promising strategy in cancer therapy by simultaneously targeting multiple pathways responsible for tumour growth and survival. Their structure comprises two or more pharmacophores connected through suitable chemical linker. These dual or multi-functional drugs can interact with several biological targets [...] Read more.

Chimeric compounds represent a promising strategy in cancer therapy by simultaneously targeting multiple pathways responsible for tumour growth and survival. Their structure comprises two or more pharmacophores connected through suitable chemical linker. These dual or multi-functional drugs can interact with several biological targets for a more pronounced pharmacological effect. In order to identify new multi-targeting agents with anticancer efficacy, we designed and synthesised a series of novel multi-functional molecules by covalently linking antitumor compounds dichloroacetate (DCA) and Nutlin-3a. The design was aimed at addressing two critical events in cancer: (1) the Warburg effect and (2) the dysregulations of protein p53 pathway, both of which are directly linked to the predominant survival and aggressive proliferation of malignant cells. DCA reactivate oxidative phosphorylation by inhibiting mitochondria pyruvate dehydrogenase kinase (PDK), thereby unlocking the Warburg metabolism of cancer cells and its antiapoptosis state. Concurrently, Nutlin-3a restores the protective function of the “genome guardian” p53 protein, by blocking its antagonist oncoprotein E3 ligase MDM2. Chimeric compounds were obtained using a chemoenzymatic multi-step procedure that included a key lipase-catalysed asymmetric reaction. Biological evaluation of the synthesised Nutlin-DCA chimeras in a panel of three cancer cell lines demonstrated promising results in vitro. Specifically, compounds rac-19a, rac-19b, rac-20a, rac-20b, and enantioenriched 20a caused a statistically significant reduction in cell viability at micromolar concentrations. These findings suggest that targeting both the Warburg effect and the p53 pathway with a single molecule is a viable approach for future cancer therapeutic development. Full article

(This article belongs to the Section Bioorganic Chemistry)

17 pages, 3070 KB

Open AccessArticle

Encapsulation of Acid Whey in Alginate Microspheres for Application in Skin Microbiome-Friendly Topical Formulations: Optimization Through a Design of Experiments Approach

by Elżbieta Sikora, Anna Łętocha, Alicja Michalczyk and Agnieszka Kozik

Molecules 2025, 30(19), 3907; https://doi.org/10.3390/molecules30193907 (registering DOI) - 28 Sep 2025

Abstract

Skin microbiome-friendly preparations are gaining increasing popularity in the cosmetics and pharmaceutical industries. Fermented plants, lysates, and heat-treated products are used as probiotic ingredients in cosmetics. This is due to the presence of Lactobacillus bacteria, such as acid or acid-rennet whey, which are [...] Read more.

Skin microbiome-friendly preparations are gaining increasing popularity in the cosmetics and pharmaceutical industries. Fermented plants, lysates, and heat-treated products are used as probiotic ingredients in cosmetics. This is due to the presence of Lactobacillus bacteria, such as acid or acid-rennet whey, which are natural probiotics that can positively impact the skin microbiome. However, due to technological difficulties, the direct use of whey as a cosmetic ingredient is limited. An optimized emulsification method was used to obtain alginate microspheres as carriers of whey. The process parameters were optimized using the Design of Experiments (DoEs) methodology. The effect of three key variables, including the type of probiotic raw material (whey from 1—cows, 2—goats, and 3—mixed), the alginate-to-raw material ratio (1–3%), and sonication time (0.5–1.5 min), on parameters such as encapsulation efficiency, bacterial survival, viscosity, and microspheres size was analyzed. The results obtained demonstrated that the optimal process parameters were the sonication time of 0.5 min and the alginate-to-whey mass ratio of 1.5% for all types of whey material studied. However, the most important factor influencing the properties and functionality of the microspheres was sonication time. The optimized whey-loaded microspheres were incorporated into a preservative-containing emulsion system, in which the viability of whey-derived bacteria was monitored over time. The whey encapsulation process effectively maintained the bacteria’s probiotic properties, protecting their viability despite the presence of preservatives (at a level of 4.92 ± 0.9 log CFU/g after 30 days of formulation storage), thus confirming the feasibility of incorporating liquid whey into skincare formulations. Full article

(This article belongs to the Special Issue Bioactive Compounds from Foods for Health Benefits)

30 pages, 1033 KB

Open AccessReview

Traditional Applications, Phytochemical Constituents, and Pharmacological Properties of Lavandula multifida L.: A Review

by Mohammed Allouani, Noui Hendel, Dahou Moutassem, Madani Sarri, Djamel Sarri, Antonella D’Anneo, Giuseppe Gallo and Antonio Palumbo Piccionello

Molecules 2025, 30(19), 3906; https://doi.org/10.3390/molecules30193906 (registering DOI) - 28 Sep 2025

Abstract

The genus Lavandula represents one of the most valuable aromatic and medicinal plants, holding significant economic importance in the pharmaceutical, food, perfumery, and cosmetics industries. Among them, L. multifida is a traditionally used medicinal plant in the Mediterranean region. This work provides a [...] Read more.

The genus Lavandula represents one of the most valuable aromatic and medicinal plants, holding significant economic importance in the pharmaceutical, food, perfumery, and cosmetics industries. Among them, L. multifida is a traditionally used medicinal plant in the Mediterranean region. This work provides a comprehensive review of L. multifida, focusing on its traditional uses, phytochemistry, and pharmacological properties. Unlike conventional lavenders, its essential oil is dominated by phenolic monoterpenes, principally carvacrol, alongside significant concentrations of β-bisabolene, 1,8-cineole, and camphor. This distinct phytochemical profile is further complemented by a rich range of non-volatile constituents, including flavonoids, phenolic acids, and triterpenoids. Pharmacological investigations have validated its broad-spectrum antimicrobial activity, demonstrating efficacy against multidrug-resistant bacterial strains and fungal pathogens through mechanisms such as membrane disruption, metabolic interference, and quorum sensing inhibition. Furthermore, the species exhibits significant antioxidant and anti-inflammatory properties, mediated primarily through radical scavenging, cyclooxygenase inhibition, and cytokine modulation. Owing to its distinct chemistry, specific traditional uses for respiratory and digestive ailments, limited endemic habitat, and underexplored status, L. multifida presents a promising candidate for future research with high potential for novel drug discovery, particularly in antiparasitic and respiratory therapies. This review concludes by identifying key research priorities for L. multifida, including a detailed analysis of its non-volatile compounds, mechanistic elucidation, toxicological assessments, and standardization of extracts. Addressing these gaps is essential to validate its traditional applications and advance its development into evidence-based phytomedicines, adjuvant therapies, and natural agrochemicals. Full article

(This article belongs to the Section Natural Products Chemistry)

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21 pages, 4111 KB

Open AccessArticle

Structural and Computational Insights into Transketolase-like 1 (TKTL-1): Distinction from TKT and Implications for Cancer Metabolism and Therapeutic Targeting

by Ahmad Junaid, Caleb J. Nwaogwugwu and Sameh H. Abdelwahed

Molecules 2025, 30(19), 3905; https://doi.org/10.3390/molecules30193905 (registering DOI) - 27 Sep 2025

Abstract

Transketolase-like protein 1 (TKTL-1) has been implicated in altered cancer metabolism, yet its structure and molecular function remain poorly understood. In this study, we established a homology model of TKTL-1 using multiple templates and validated it through sequence alignment and structural comparison with [...] Read more.

Transketolase-like protein 1 (TKTL-1) has been implicated in altered cancer metabolism, yet its structure and molecular function remain poorly understood. In this study, we established a homology model of TKTL-1 using multiple templates and validated it through sequence alignment and structural comparison with the canonical transketolase (TKT). Binding-site identification was performed using CASTp, receptor cavity mapping, and blind docking, all of which consistently pointed to a conserved region involving interactive residues shared between TKT and TKTL-1. Comparative docking revealed the reduced affinity of TKTL-1 for TDP, supporting functional divergence between TKTL-1 and TKT. We further analyzed conserved residues and receptor surfaces, which enabled us to propose predictive scaffolds as potential modulators of TKTL-1. While these scaffolds remain theoretical, they provide a computational framework to guide future pharmacophore modeling, molecular dynamics simulations, and experimental validation. Together, our study highlights the structural features of TKTL-1, establishes its key differences from TKT, and lays the groundwork for future drug discovery efforts targeting cancer metabolism. Full article

(This article belongs to the Special Issue Small-Molecule Drug Design and Discovery)

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25 pages, 1444 KB

Open AccessArticle

Spray-Drying Microencapsulation of Artemisia herba-alba Phenolic Extract: Physicochemical Properties, Structural Characterization, and Bioactivity

by Sara Lemmadi, Emilie Dumas, Faïza Adoui, Géraldine Agusti, Séverine Vessot-Crastes, Wafa Medfai and Adem Gharsallaoui

Molecules 2025, 30(19), 3904; https://doi.org/10.3390/molecules30193904 (registering DOI) - 27 Sep 2025

Abstract

Artemisia herba-alba Asso. is a medicinal plant rich in phenolic compounds with strong antioxidant and antimicrobial activities. However, these bioactive molecules are highly sensitive to environmental conditions, limiting their stability and potential applications. This study investigated, for the first time, the encapsulation of [...] Read more.

Artemisia herba-alba Asso. is a medicinal plant rich in phenolic compounds with strong antioxidant and antimicrobial activities. However, these bioactive molecules are highly sensitive to environmental conditions, limiting their stability and potential applications. This study investigated, for the first time, the encapsulation of ethanolic extracts from the aerial parts of A. herba-alba by spray-drying, using maltodextrin (MD) and sodium caseinate (SC) as wall materials. The extract was obtained by ultrasound-assisted extraction, and both free and encapsulated forms were analyzed for phytochemical composition, antioxidant capacity, and antibacterial activity. Spray-dried microcapsules (SDE) were further characterized for encapsulation yield, efficiency, moisture, water activity, hygroscopicity, particle size, and structural integrity (SEM, ATR-FTIR, TGA/DTG). The process resulted in a high encapsulation yield (69.40%) and efficiency (96.39%), producing microcapsules with a small average size (10.05 ± 0.08 µm), low moisture (4.34%), low water activity (0.415), and moderate hygroscopicity (12.67%). Although the encapsulated extract showed lower total phenolic content, antioxidant capacity, and antibacterial activity compared to the free extract, SEM observations confirmed the formation of spherical, crack-free microcapsules, ATR-FTIR analysis revealed non-covalent interactions between wall materials and phenolics, and TGA/DTG demonstrated improved thermal stability. These results highlight spray-drying microencapsulation as an efficient approach to stabilize A. herba-alba phenolic compounds, offering promising applications as natural preservatives in the food industry. Full article

(This article belongs to the Special Issue Innovative Strategies for the Extraction, Processing, and Encapsulation of Food Bioactive Compounds)

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23 pages, 748 KB

Open AccessReview

Polyamine Induction of Secondary Metabolite Biosynthetic Genes in Fungi Is Mediated by Global Regulator LaeA and α-NAC Transcriptional Coactivator: Connection to Epigenetic Modification of Histones

by Juan F. Martín

Molecules 2025, 30(19), 3903; https://doi.org/10.3390/molecules30193903 (registering DOI) - 27 Sep 2025

Abstract

Polyamines are polycationic compounds present in all living cells that exert functions at different levels in the metabolism. They bind to DNA and RNA and modulate DNA replication and gene expression. Some of these regulatory effects are exerted by promoting condensation of nucleosomes, [...] Read more.

Polyamines are polycationic compounds present in all living cells that exert functions at different levels in the metabolism. They bind to DNA and RNA and modulate DNA replication and gene expression. Some of these regulatory effects are exerted by promoting condensation of nucleosomes, a mechanism closely connected with epigenetic modification by histone methylation and acetylation. The polyamines 1,3-diaminopropane and spermidine induce expression of the global regulator LaeA and increase by several folds the formation of the α-NAC transcriptional co-activator, a subunit of the nascent polypeptide-associated complex. The global regulator LaeA controls the switch from primary growth to secondary metabolite production and differentiation when an essential nutrient in the growth medium becomes limiting. α-NAC exerts significant control over the biosynthesis of secondary metabolites and fungal pathogenicity on plants. When purified α-NAC protein is added to a tomato host plant, it induces plant resistance to fungal infections and triggers the development of system-acquired resistance in other plants. Spermidine extends the life of yeast cells and prolongs the half-life of penicillin gene transcripts in Penicillium chrysogenum. This article discusses advances in the basis of understanding the mechanism of plant–fungi interaction and the effect of small fungal metabolites and epigenetic modifiers in this interaction. Full article

(This article belongs to the Special Issue Natural Products Biosynthesis: Present and Perspectives)

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18 pages, 2374 KB

Open AccessArticle

Fluorescent Dihomooxacalix[4]arenes for the Detection of Nitroaromatic Compounds in Solution and in the Vapour Phase: Structural and Supramolecular Insights

by Beatriz V. Gil, Alexandre S. Miranda, Paula M. Marcos, José R. Ascenso, Tiago Palmeira, Mário N. Berberan-Santos, Rachel Schurhammer, Neal Hickey, Siddharth Joshi and Silvano Geremia

Molecules 2025, 30(19), 3901; https://doi.org/10.3390/molecules30193901 (registering DOI) - 27 Sep 2025

Abstract

Two fluorescent ureido-dihomooxacalix[4]arene derivatives containing naphthyl residues at the lower rim (1 and 2) were studied for the detection of nitroaromatic compounds (NACs) in solution and in vapour phases. Their affinity in solution was determined by UV-Vis absorption, fluorescence and NMR [...] Read more.

Two fluorescent ureido-dihomooxacalix[4]arene derivatives containing naphthyl residues at the lower rim (1 and 2) were studied for the detection of nitroaromatic compounds (NACs) in solution and in vapour phases. Their affinity in solution was determined by UV-Vis absorption, fluorescence and NMR spectroscopy. For NAC vapour sensing, calixarenes were dispersed in a polytetrafluoroethylene (PTFE) matrix. Four new solvated crystals of dihomooxacalix[4]arene 2 were obtained and the solvent’s influence on its structural characteristics was investigated. The solvent-dependent structural variations observed in the crystal structures highlight the intrinsic flexibility of the calixarene framework. Such conformational adaptability, evident in the disruption and reorganization of hydrogen bonding and π–π interactions, is directly relevant to nitroaromatic sensing, where a rapid and reversible host response is crucial for effective detection. Theoretical calculations were also performed to provide further insights on the binding process. The corrected Stern–Volmer constants (K_SV) obtained showed that both receptors present selectivity for TNP and follow the same quenching order (TNP > NT > NB > DNT > TNT > DNB). Factors other than electron density distribution should dominate the quenching extent and therefore the values of the SV constants, which will be greatly overestimated if no correction to the inner filter effect is applied. Detection of NB and NT and vapours by both calixarenes produced a complete, very fast (2 to 5 s), and reversible quenching, indicating the potential use of this porous PTFE–calixarene matrix for the sensing of volatile NACs. Full article

(This article belongs to the Section Organic Chemistry)

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21 pages, 1599 KB

Open AccessArticle

Development and Validation of HPLC-DAD/FLD Methods for the Determination of Vitamins B₁, B₂, and B₆ in Pharmaceutical Gummies and Gastrointestinal Fluids—In Vitro Digestion Studies in Different Nutritional Habits

by Georgios Kamaris, Nikoletta Pantoudi and Catherine K. Markopoulou

Molecules 2025, 30(19), 3902; https://doi.org/10.3390/molecules30193902 (registering DOI) - 26 Sep 2025

Abstract

Two HPLC-based analytical methods, one with DAD and the other with an FLD detector, were developed and validated for the simultaneous analysis of B₁, B₂, and B₆ vitamins, both in pharmaceutical gummies and in gastric and intestinal fluids [...] Read more.

Two HPLC-based analytical methods, one with DAD and the other with an FLD detector, were developed and validated for the simultaneous analysis of B₁, B₂, and B₆ vitamins, both in pharmaceutical gummies and in gastric and intestinal fluids (with water or milk or orange juice). For the detection of B₁ by fluorometry, a pre-column oxidation/derivatization process was accomplished in the presence of B₂ and B₆ vitamins. The methods were performed on an Aqua column (250 mm × 4.6 mm, 5 mm) at 40 °C, with isocratic elution (70% NaH₂PO₄ buffer pH 4.95 and 30% methanol) and a flow rate of 0.9 mL/min. Both were validated according to ICH specifications in terms of linearity (R² > 0.999), accuracy (% Mean Recovery 100 ± 3%) and precision (%RSD < 3.23). For the analysis of the samples, a stability study (in diluents, pH and fluids) was conducted, while for their purification two different extraction procedures, a liquid/solid for the gummies (%Recovery > 99.8%) and a Solid Phase Extraction (SPE) for the Gastrointestinal (G.I.) fluids, (%Recovery 100 ± 5%) were developed. Finally, to investigate whether the co-administration of B-complex with water, orange juice or milk plays a significant role in their release from gummies, a three-phase in vitro digestion protocol was applied. The results did not show significant differences with a slight superiority in the release of B₂ and B₆ with water, while B₁ with orange juice. Full article

(This article belongs to the Special Issue Extraction Techniques for Sample Preparation)

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14 pages, 2557 KB

Open AccessArticle

Composite Material Formation Based on Biochar and Nickel (II)-Copper (II) Ferrites

by Nina P. Shabelskaya, Alexandr V. Vyaltsev, Neonilla G. Sundukova, Vera A. Baranova, Sergej I. Sulima, Elena V. Sulima, Yulia A. Gaidukova, Asatullo M. Radzhbov, Elena V. Vasileva and Elena A. Yakovenko

Molecules 2025, 30(19), 3900; https://doi.org/10.3390/molecules30193900 - 26 Sep 2025

Abstract

This paper studies the formation process of a composite material based on an organic substance, biochar from sunflower husks, and an inorganic substance, nickel (II)-copper (II) ferrites of the composition Cu_xNi_1−xFe₂O₄ (x = 0.0; 0.5; 1.0). [...] Read more.

This paper studies the formation process of a composite material based on an organic substance, biochar from sunflower husks, and an inorganic substance, nickel (II)-copper (II) ferrites of the composition Cu_xNi_1−xFe₂O₄ (x = 0.0; 0.5; 1.0). The obtained materials were characterized by X-ray phase analysis, scanning electron microscopy, and FTIR spectroscopy. It is shown that when replacing copper (II) cations with nickel (II) cations, the average parameters and volume of the unit cell gradually decrease, and the cation–anion distances in both the tetrahedral and octahedral spinel grids also decrease with regularity. The oxide materials were found to form a film on the surface of biochar, repeating its porous structure. The obtained materials exhibit high catalytic activity in the methyl orange decomposition reaction under the action of hydrogen peroxide in an acidic medium; the degradation of methyl orange in an aqueous solution occurs 30 min after the start of the reaction. This result may be associated with the formation of the Fenton system during the oxidation–reduction process. A significant increase in the reaction rate in the system containing mixed nickel–copper ferrite as a catalyst may be associated with the formation of a more defective structure due to the Jahn–Teller effect manifestation, which creates additional active centers on the catalyst surface. Full article

(This article belongs to the Special Issue Green Synthesis and Environmental Application of Biomass-Based Materials)

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14 pages, 1928 KB

Open AccessArticle

The Pharmacokinetics, Bioavailability, and Excretion Studies of α-Cyperone in Rats by UHPLC-QQQ-MS/MS

by Ye Shang, Yameng Zhu, Kaili Zhang, Zijing Zhang, Huining Geng, Xueyu Liu, Wenwen Li, Lu Chen, Caixia Li, Yang Liu, Huizi Ouyang and Jun He

Molecules 2025, 30(19), 3899; https://doi.org/10.3390/molecules30193899 (registering DOI) - 26 Sep 2025

Abstract

α-Cyperone (C₁₅H₂₂O), a critical bioactive sesquiterpene, serves as a representative chemical compound of Cyperi Rhizoma—a classical functional food. To investigate the pharmacokinetic characteristics of α-cyperone, a quantified method was developed in plasma, bile, urine, and feces by [...] Read more.

α-Cyperone (C₁₅H₂₂O), a critical bioactive sesquiterpene, serves as a representative chemical compound of Cyperi Rhizoma—a classical functional food. To investigate the pharmacokinetic characteristics of α-cyperone, a quantified method was developed in plasma, bile, urine, and feces by ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS). After being validated, the developed method was applied in a plasma pharmacokinetic study as well as biliary, urinary, and fecal excretion kinetics studies. It revealed poor absolute bioavailability (F = 1.36%) and rare excretion (total cumulative excretion = 0.022%) of α-cyperone, which suggested extensive first-pass metabolism. This study provided crucial insight into explaining the in vivo process and promoting the further development of α-cyperone. Full article

(This article belongs to the Section Analytical Chemistry)

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18 pages, 3473 KB

Open AccessArticle

Calorimetric Studies of the Silver-Titanium System

by Weronika Gozdur, Wojciech Gierlotka, Władysław Gąsior, Anna Wierzbicka-Miernik, Tomasz Czeppe, Andrzej Budziak, Agata Radziwonko, Magda Pęska and Adam Dębski

Molecules 2025, 30(19), 3898; https://doi.org/10.3390/molecules30193898 - 26 Sep 2025

Abstract

Alloys from the Ag-Ti system are extremely promising and offer the possibility of versatile applications owing to their attractive properties. However, due to the experimental difficulties caused, among others, by the significant difference in melting points of the components, most of the information [...] Read more.

Alloys from the Ag-Ti system are extremely promising and offer the possibility of versatile applications owing to their attractive properties. However, due to the experimental difficulties caused, among others, by the significant difference in melting points of the components, most of the information on the thermodynamic properties available in the literature has been obtained by computer methods. Therefore, the main aim of this work is to extend the current knowledge about the experimentally determined thermodynamic properties of selected alloys from the Ag-Ti system. Within the scope of this work, calorimetric studies were carried out using Differential Scanning Calorimetry (DSC) and high-temperature drop calorimetry measurements. The first of the aforementioned methods was used to determine the characteristic temperature of the Ag_0.43Ti_0.57 alloy synthesized by mechanical alloying. Using titanium hydride instead of titanium for the preparation of alloys from the Ag-Ti system has not yet been reported in the literature. This paper presents a complete structural characterization (SEM, XRD studies) of the above alloy produced by this method. The second technique was applied to ascertain the mixing enthalpy change in the alloys in the composition range between x_Ti = 0.02–0.226, and for the measurements of the formation enthalpy of the AgTi intermetallic phase. Based on the calorimetric results obtained in this study, along with the relevant thermodynamic data from the literature, the Ag-Ti phase diagram was reoptimized. Full article

(This article belongs to the Special Issue Recent Advances in Chemical Thermodynamics from Theory to Experiment)

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13 pages, 621 KB

Open AccessArticle

5-Hydroxymethylfurfural: A Particularly Harmful Molecule Inducing Toxic Lipids and Proteins?

by Joachim Greilberger, Georg Feigl, Matthias Greilberger, Simona Bystrianska and Michaela Greilberger

Molecules 2025, 30(19), 3897; https://doi.org/10.3390/molecules30193897 - 26 Sep 2025

Abstract

Introduction: 5-HMF is a molecule found in carbohydrate-rich foods that is associated not only with cancer and anaphylactic reactions, but also with anti-oxidant properties. Questions arose as to whether 5-HMF exhibited a catalytic effect in relation to lipid peroxidation and lipoprotein oxidation in [...] Read more.

Introduction: 5-HMF is a molecule found in carbohydrate-rich foods that is associated not only with cancer and anaphylactic reactions, but also with anti-oxidant properties. Questions arose as to whether 5-HMF exhibited a catalytic effect in relation to lipid peroxidation and lipoprotein oxidation in presence of metals and/or radicals. Methods: Peroxynitrite (ONOO⁻)-induced chemiluminescence and ONOO⁻ nitration of tyrosine residues on BSA using anti-nitro-tyrosine-antibodies were used to measure the protection of 5-HMF against peroxides or nitration compared to vitamin C (VitC). The reductive potential of 5-HMF or VitC on Cu²⁺ or Fe³ was estimated using the bicinchoninic acid (BCA) or Fenton-complex method. Human plasma was used to measure the generation of malondialdehyde (MDA), 4-hydroxynonenal (HNE), and total thiols after Fe²⁺/H₂O₂ oxidation in the presence of different concentrations of 5-HMF or VitC. Finally, Cu²⁺ oxidation of LDL after 4 h was carried out with 5-HMF or VitC, measuring the concentration of MDA in LDL with the thiobarbituric assay (TBARS). Results: VitC was 4-fold more effective than 5-HMF in scavenging ONOO⁻ to nearly 91.5% at 4 mM, with the exception of 0.16 mM, where the reduction of ONOO⁻ by VitC was 3.3-fold weaker compared to 0.16 mM 5-HMF. VitC or 5-HMF at a concentration of 6 mM inhibited the nitration of tyrosine residues on BSA to nearly 90% with a similar course. While 5-HMF reduced free Fe³⁺ in presence of phenanthroline, forming Fe²⁺ (phenantroleine)₃ [Fe²⁺(phe)₃] or complexed Cu²⁺(BCA)₄ to Cu⁺(BCA)₄ weakly, VitC was 7- to 19-fold effective in doing so over all the used concentrations (0–25 mM). A Fe²⁺—H₂O₂ solution mixed with human plasma showed a 6–10 times higher optical density (OD) of MDA or HNE in the presence of 5-HMF compared to VitC. The level of thiols was significantly decreased in the presence of higher VitC levels (1 mM: 198.4 ± 7.7 µM; 2 mM: 160.0 ± 13.4 µM) compared to equal 5-HMF amounts (2562 ± 7.8 µM or 242.4 ± 2.5 µM), whereas the usage of lower levels at 0.25 µM 5-HMF resulted in a significant decrease in thiols (272.4 ± 4.0 µM) compared to VitC (312.3 ± 19.7 µM). Both VitC and 5-HMF accelerated copper-mediated oxidation of LDL equally: while the TBARS levels from 4 h oxidized LDL reached 137.7 ± 12.3 nmol/mg, it was 1.7-fold higher using 6 mM VitC (259.9 ± 10.4 nmol/mg) or 6 mM 5-HMF (239.3 ± 10.2 nmol/mg). Conclusions: 5-HMF appeared to have more pro-oxidative potential compared to VitC by causing lipid peroxidation as well as protein oxidation. Full article

(This article belongs to the Special Issue Research Progress on Functional Lipids and Their Applications in Health Food Systems)

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