Molecules

25 pages, 3037 KB

Open AccessArticle

Changes in Resveratrol Containing Phytosterol Liposomes During Model Heating

by Joanna Igielska-Kalwat, Magdalena Rudzińska, Anna Grygier, Dominik Kmiecik, Katarzyna Cieślik-Boczula and Jolanta Tomaszewska-Gras

Molecules 2025, 30(23), 4645; https://doi.org/10.3390/molecules30234645 (registering DOI) - 3 Dec 2025

Abstract

Background: Phytosterols are bioactive lipids susceptible to oxidation, particularly under thermal stress. Incorporation into liposomes may enhance their stability, while resveratrol—a natural antioxidant—could further limit thermal degradation. Stigmasterol esters, which contain fatty acid residues prone to oxidation, require additional characterization to understand their [...] Read more.

Background: Phytosterols are bioactive lipids susceptible to oxidation, particularly under thermal stress. Incorporation into liposomes may enhance their stability, while resveratrol—a natural antioxidant—could further limit thermal degradation. Stigmasterol esters, which contain fatty acid residues prone to oxidation, require additional characterization to understand their behavior under heating. Methods: Liposomes composed of dipalmitoylphosphatidylcholine (DPPC) were enriched with free stigmasterol (ST), stigmasteryl myristate (ME), or stigmasteryl oleate (OE), with or without resveratrol (RES). Liposomal systems were characterized using transmission electron microscopy, zeta potential, and hydrodynamic diameter analyses. Samples were heated at 60 °C and 180 °C for 8 h to evaluate stigmasterol degradation, oxyphytosterol (SOP) formation, and decomposition of fatty acid residues in the esters. Results: Liposomes remained structurally stable at 60 °C but underwent marked alterations at 180 °C. ST formed the smallest particles, while ME and OE systems exhibited larger hydrodynamic diameters. Incorporation of resveratrol enhanced thermal and oxidative stability, reducing stigmasterol degradation (7.73–18.86% at 60 °C; 29.66–35.28% at 180 °C) and limiting SOP formation. Differences in the breakdown of myristic versus oleic acid residues highlighted the role of fatty acid type in determining thermal resistance. Conclusions: Resveratrol effectively improves the stability of liposomes containing stigmasterol or its esters and mitigates oxidative damage under thermal stress. Protective effects were particularly evident at moderate temperatures, indicating the potential of resveratrol–phytosterol liposomes as thermally stable delivery systems. Full article

(This article belongs to the Special Issue Exploring the Antioxidant Activity of Natural Extracts: New Findings and Potential Food- and Non-Food-Related Applications)

11 pages, 3801 KB

Open AccessArticle

Study on the Hygroscopic Properties and Mechanism of Novel Melt-Cast Matrix 3,4-Dinitropyrazole (DNP)

by Tong Guan, Yuehui Yue, Wujiang Ying, Bo Yan, Pan Liu and Xiangrong Zhang

Molecules 2025, 30(23), 4644; https://doi.org/10.3390/molecules30234644 (registering DOI) - 3 Dec 2025

Abstract

3,4-Dinitropyrazole (DNP) is a promising candidate as a next-generation matrix for melt-cast explosives. However, its hygroscopicity severely limits the application of DNP. In this work, the macroscopic hygroscopic properties of DNP powder and charge were determined through moisture absorption tests under varying temperature [...] Read more.

3,4-Dinitropyrazole (DNP) is a promising candidate as a next-generation matrix for melt-cast explosives. However, its hygroscopicity severely limits the application of DNP. In this work, the macroscopic hygroscopic properties of DNP powder and charge were determined through moisture absorption tests under varying temperature and relative humidity (RH) conditions. At the micrometer scale, the morphological evolution after moisture absorption was observed by scanning electron microscopy (SEM). The moisture absorption mechanism of DNP at the molecular level was elucidated using Raman spectroscopy. The results demonstrate that the hygroscopicity of DNP intensifies with rising temperature and RH. The critical relative humidity (CRH) was determined to be 85% at 25 °C, 62% at 40 °C, and 42% at 55 °C. The surface of dried DNP particles exhibits a highly developed porous structure conducive to moisture adsorption from the environment. The moisture absorption mechanism of DNP involves water molecules forming hydrogen bonds with both the N–H bonds and nitro groups of DNP molecules. The hydrogen bonds between water and DNP molecules replace the original N-H···O/N hydrogen-bond network within the DNP crystal and disrupt the intermolecular π-π stacking interactions. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 4377 KB

Open AccessArticle

Plasmon-Enhanced Piezo-Photocatalytic Degradation of Metronidazole Using Ag-Decorated ZnO Microtetrapods

by Farid Orudzhev, Makhach Gadzhiev, Rashid Gyulakhmedov, Sergey Antipov, Arsen Muslimov, Valeriya Krasnova, Maksim Il’ichev, Yury Kulikov, Andrey Chistolinov, Damir Yusupov, Ivan Volchkov, Alexander Tyuftyaev and Vladimir Kanevsky

Molecules 2025, 30(23), 4643; https://doi.org/10.3390/molecules30234643 (registering DOI) - 3 Dec 2025

Abstract

The development of advanced semiconductor-based catalysts for the rapid degradation of emerging pharmaceutical pollutants in water remains a critical challenge in environmental science. In this study, we present the synthesis, characterization, and catalytic performance of zinc oxide (ZnO) microtetrapods decorated with plasmonic Ag [...] Read more.

The development of advanced semiconductor-based catalysts for the rapid degradation of emerging pharmaceutical pollutants in water remains a critical challenge in environmental science. In this study, we present the synthesis, characterization, and catalytic performance of zinc oxide (ZnO) microtetrapods decorated with plasmonic Ag nanoparticles. These microtetrapods have been designed to enhance piezo-, photo-, and piezo-photocatalytic degradation of metronidazole (MNZ), a persistent antibiotic contaminant. ZnO microtetrapods were synthesized by high-temperature pyrolysis and using atmospheric-pressure microwave nitrogen plasma, followed by photochemical deposition of Ag nanoparticles at various precursor concentrations (0–1 mmol AgNO₃). The structural integrity of the samples was confirmed through X-ray diffraction (XRD) analysis, while the morphology was examined using scanning electron microscopy with energy-dispersive X-ray analysis (SEM-EDX). Additionally, spectroscopic analysis, including Raman, electron paramagnetic resonance (EPR), and photoluminescence (PL) spectroscopy, was conducted to verify the successful formation of heterostructures with adjustable surface loading of Ag. It has been shown that ZnO microtetrapods decorated with plasmonic Ag nanoparticles exhibit Raman-active properties. A systematic evaluation under photocatalytic, piezocatalytic, and combined piezo-photocatalytic conditions revealed a pronounced volcano-type dependence of catalytic activity on Ag content, with the 0.75 mmol composition exhibiting optimal performance. In the presence of both light irradiation and ultrasonication, the optimized Ag/ZnO composite exhibited 93% degradation of MNZ within a span of 5 min, accompanied by an apparent rate constant of 0.56 min⁻¹. This value stands as a significant improvement, surpassing the degradation rate of pristine ZnO by over 24-fold. The collective identification of defect modulation, plasmon-induced charge separation, and piezoelectric polarization as the predominant mechanisms driving enhanced reactive oxygen species (ROS) generation is a significant advancement in the field. These findings underscore the synergistic interplay between plasmonic and piezoelectric effects in oxide-based heterostructures and present a promising strategy for the efficient removal of recalcitrant water pollutants using multi-field activated catalysis. Full article

(This article belongs to the Special Issue Photocatalytic Materials and Photocatalytic Reactions, 2nd Edition)

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15 pages, 1737 KB

Open AccessArticle

Volatile Organic Compounds Induced upon Viral Infection in Cell Culture: Uniform Background Study with Use of Viruses from Different Families

by Anna Karolina Matczuk, Julia Wolska, Maria Olszowy, Agata Kublicka, Adam Szumowski, Agata Kokocińska-Alexandre, Michał Dzięcioł, Jacek Łyczko, Martyna Woszczyło, Marcin J. Skwark and Antoni Szumny

Molecules 2025, 30(23), 4642; https://doi.org/10.3390/molecules30234642 (registering DOI) - 3 Dec 2025

Abstract

This study investigates the production of volatile organic compounds (VOCs) in RK-13 cells infected with three equine viruses representing different families: equine arteritis virus (EAV) (Arteriviridae), equine herpesvirus 1 (EHV-1) (Herpesviridae), and equine rhinitis B virus (ERBV) (Picornaviridae [...] Read more.

This study investigates the production of volatile organic compounds (VOCs) in RK-13 cells infected with three equine viruses representing different families: equine arteritis virus (EAV) (Arteriviridae), equine herpesvirus 1 (EHV-1) (Herpesviridae), and equine rhinitis B virus (ERBV) (Picornaviridae). VOCs, which are byproducts of cellular metabolism and potential non-invasive diagnostic markers, were analyzed using headspace solid-phase microextraction (HS-SPME) and gas chromatography–mass spectrometry (GC-MS). Since viruses do not possess intrinsic metabolic activity, the observed changes in the VOC profiles were attributed to host responses, such as metabolic reprogramming, oxidative stress, and apoptosis. We hypothesized that each viral infection induces distinct metabolic changes, resulting in characteristic VOC signatures that mirror the virus type, replication kinetics, and cytopathic effects. Notably, viruses with rapid cytopathic effects (e.g., EHV-1) were anticipated to trigger more pronounced VOC alterations. In our experimental design, RK-13 cells were infected at a multiplicity of infection of 1 and incubated for 24 h, 48 h, or 72 h. Distinct VOC profiles emerged, with significant elevations in compounds like 2-ethyl-1-hexanol, particularly in EHV-1 infections, and selective increases in acetophenone and benzaldehyde. Principal component analysis (PCA) of the VOC concentration data showed the clear separation of data from viruses from different families. These findings support the potential of VOC profiling as a rapid diagnostic tool for viral infections. Full article

(This article belongs to the Special Issue Analysis of Natural Volatile Organic Compounds (NVOCs))

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14 pages, 3474 KB

Open AccessArticle

Iohexol as an Emerging Contaminant Potentially Influencing Structural and Functional Changes in the Activated Sludge Microbiome

by Agnieszka Nowak, Magdalena Pacwa-Płociniczak, Urszula Guzik and Danuta Wojcieszyńska

Molecules 2025, 30(23), 4641; https://doi.org/10.3390/molecules30234641 (registering DOI) - 3 Dec 2025

Abstract

Iohexol (IOX) is one of the most commonly used iodinated contrast agents due to its relatively low toxicity. However, owing to its low biodegradability, it accumulates in wastewater and sewage sludge, ultimately reaching wastewater treatment plants. With increasing IOX loads, the activated sludge [...] Read more.

Iohexol (IOX) is one of the most commonly used iodinated contrast agents due to its relatively low toxicity. However, owing to its low biodegradability, it accumulates in wastewater and sewage sludge, ultimately reaching wastewater treatment plants. With increasing IOX loads, the activated sludge (AS) microbiome is exposed to its long-term effects. Therefore, this study aimed to determine the impact of IOX on the structure and functioning of AS. The results demonstrated that IOX at lower concentrations does not affect the functional parameters of AS, and only long-term exposure of the microbiome to a concentration of 20 mg/L results in functional changes. These changes themselves, among other effects, concerning amino acid and carbohydrate metabolism and the phosphorus cycle. Furthermore, the study demonstrated that despite the activated sludge microbiome’s ability to transform 20 mg/L of IOX, long-term exposure to this concentration reduces the efficiency of this process. This indicates that although IOX is a relatively safe compound, prolonged exposure of the AS microbiome to high doses may lead to functional changes in AS and potentially impair wastewater treatment processes. Full article

(This article belongs to the Special Issue Determination, Adsorption and Degradation Mechanisms of Environmental Pollutants)

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16 pages, 3531 KB

Open AccessArticle

Corrosion, Wear, and Fretting Corrosion Properties of Cr/CrN and Mo/MoN Multilayer Coatings with Biomedical Potential

by Lin Chen, Bingyan Chen, Boxing Han, Heng Liu, Tianyi Zhang and Baojun Dong

Molecules 2025, 30(23), 4640; https://doi.org/10.3390/molecules30234640 (registering DOI) - 3 Dec 2025

Abstract

In this study, Cr/CrN and Mo/MoN alternating multilayer coatings with pure metal interlayers were deposited on 316 L stainless steel substrates via physical vapor deposition to systematically investigate the corrosion resistance, wear resistance, and tribocorrosion behavior of the multilayer coating systems in physiological [...] Read more.

In this study, Cr/CrN and Mo/MoN alternating multilayer coatings with pure metal interlayers were deposited on 316 L stainless steel substrates via physical vapor deposition to systematically investigate the corrosion resistance, wear resistance, and tribocorrosion behavior of the multilayer coating systems in physiological saline environments. Microstructural characterization revealed that the CrN layer consists of mixed CrN and Cr₂N phases, whereas the MoN layer exhibits a highly densified microstructure along with the presence of MoO₂ phase, which collectively contribute to the superior corrosion resistance of the Mo/MoN coating. Furthermore, compared to the CrN layer, the MoN layer demonstrates enhanced nanomechanical properties and improved resistance to crack initiation, due to the greater hardness and higher H/E and H³/E² values. Consequently, the Mo/MoN coating exhibits significantly better wear and tribocorrosion performance than its CrN counterpart. This work provides a theoretical foundation for the design of tribocorrosion-resistant hard coatings for artificial joint materials. Full article

(This article belongs to the Special Issue Corrosion Mechanisms and Protection Technologies of Metallic Materials Under Harsh Environments)

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17 pages, 3142 KB

Open AccessArticle

Novel Organosilicon Tetramers with Dialkyl-Substituted [1]Benzothieno[3,2-b]benzothiophene Moieties for Solution-Processible Organic Electronics

by Irina O. Gudkova, Evgeniy A. Zaborin, Alexander I. Buzin, Artem V. Bakirov, Yaroslava O. Titova, Oleg V. Borshchev, Sergey N. Chvalun and Sergey A. Ponomarenko

Molecules 2025, 30(23), 4639; https://doi.org/10.3390/molecules30234639 (registering DOI) - 3 Dec 2025

Abstract

The synthesis, phase behavior and semiconductor properties of two novel organosilicon tetramers with dialkyl-substituted [1]benzothieno[3,2-b]benzothiophene (BTBT) moieties, D4-Und-BTBT-Hex and D4-Hex-BTBT-Oct, are described. The synthesis of these molecules was carried out by sequential modification of the BTBT core by carbonyl-containing functional alkyl substituents [...] Read more.

The synthesis, phase behavior and semiconductor properties of two novel organosilicon tetramers with dialkyl-substituted [1]benzothieno[3,2-b]benzothiophene (BTBT) moieties, D4-Und-BTBT-Hex and D4-Hex-BTBT-Oct, are described. The synthesis of these molecules was carried out by sequential modification of the BTBT core by carbonyl-containing functional alkyl substituents using the Friedel–Crafts reaction, followed by the reduction in the keto group. The target tetramers, D4-Und-BTBT-Hex and D4-Hex-BTBT-Oct, were obtained by the hydrosilylation reaction between tetraallylsilane and corresponding 1,1,3,3-tetramethyl-1-(ω-(7-alkyl[1]benzothieno[3,2-b]benzothiophen-2-yl)alkyl)disiloxanes. The chemical structure of the compounds obtained was confirmed by NMR ¹H-, ¹³C- and ²⁹Si-spectroscopy, gel permeation chromatography and elemental analysis. Their phase behavior was investigated by differential scanning calorimetry, polarization optical microscopy and X-ray diffraction analysis. It was found that D4-Und-BTBT-Hex shows higher crystallinity at room temperature as compared to D4-Hex-BTBT-Oct, while both molecules possess smectic ordering favorable for active layer formation in organic field-effect transistors (OFETs). The active layers were applied by spin-coating under conditions of a homogeneous thin layer formation with a low content of defects. The devices obtained from D4-Und-BTBT-Hex have demonstrated good semiconductor characteristics in OFETs with a hole mobility up to 3.5 × 10⁻² cm² V⁻¹ s⁻¹, a low threshold voltage and an on/off ratio up to 10⁷. Full article

(This article belongs to the Section Cross-Field Chemistry)

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2 pages, 886 KB

Open AccessCorrection

Correction: Wang et al. Tryptanthrin Protects Mice against Dextran Sulfate Sodium-Induced Colitis through Inhibition of TNF-α/NF-κB and IL-6/STAT3 Pathways. Molecules 2018, 23, 1062

by Zheng Wang, Xue Wu, Cui-Ling Wang, Li Wang, Chen Sun, Dong-Bo Zhang, Jian-Li Liu, Yan-Ni Liang, Dong-Xin Tang and Zhi-Shu Tang

Molecules 2025, 30(23), 4638; https://doi.org/10.3390/molecules30234638 (registering DOI) - 3 Dec 2025

Abstract

In the original publication [...] Full article

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10 pages, 818 KB

Open AccessArticle

Aldose Reductase Inhibition by Orthosiphon stamineus Extracts and Constituents Suggests Antioxidant Potential

by Yousaf Dawood, Atheer Zgair, Mun Fei Yam and Nur Hidayah Kaz Abdul Aziz

Molecules 2025, 30(23), 4637; https://doi.org/10.3390/molecules30234637 (registering DOI) - 2 Dec 2025

Abstract

Background/Objectives: Aldose reductase (AR) plays a crucial role in the accumulation of oxidative factors that lead to oxidative stress-related neuroinflammation. This study aims to find a novel agent from natural sources that can inhibit AR. Methods: Different extracts of Orthosiphon stamineus Benth (OS) [...] Read more.

Background/Objectives: Aldose reductase (AR) plays a crucial role in the accumulation of oxidative factors that lead to oxidative stress-related neuroinflammation. This study aims to find a novel agent from natural sources that can inhibit AR. Methods: Different extracts of Orthosiphon stamineus Benth (OS) leaves and its active constituents, eupatorin (EUP), rosmarinic acid (RA), sinensetin (SEN) and 3-hydroxy-5,6,7,4-tetramethoxyflavone (TMF), were used to identify the potential inhibition effect of AR. A new high-performance liquid chromatography (HPLC) method was developed to determine these phytochemicals using the Shimadzu LC-20AD HPLC system. In addition, the in vitro inhibition effect of OS ethanol extracts (95% and 50%) and OS components EUP, RA, and SEN was investigated in recombinant AR (AKR1B1). Results: In this study, the developed HPLC method was precise and accurate, and demonstrated clear separation of the four compounds—EUP, RA, SEN, and TMF—in the ethanolic extract. The contents of the four selected compounds—EUP, RA, SEN, and TMF—in 95% ethanolic extract were 2.35, 11.91, 0.94, and 0.18%, respectively. RA showed the highest concentration among the selected compounds, indicating that RA is the major constituent of this plant. The in vitro assay showed significant inhibition of the AR enzyme by RA and OS ethanol extracts 95% and 50% (IC₅₀: 41.42 µM; 63.42 µg/mL and 93.22 µg/mL, respectively). Conclusions: The ethanolic extract of OS and RA could be a promising therapeutics option for the treatment of oxidative stress-related neuroinflammation disorders by inhibiting AR. Full article

(This article belongs to the Special Issue Redox-Active Molecules as Key Players for Inflammatory Diseases)

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23 pages, 8344 KB

Open AccessArticle

Discovery of Influenza Neuraminidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation of Novel Chemotypes

by Rosaria Gitto, Lisa Lombardo, Angela Ravenda, Francesco Broccolo, Antonio Mastino, Laura De Luca and Francesca Marino-Merlo

Molecules 2025, 30(23), 4636; https://doi.org/10.3390/molecules30234636 (registering DOI) - 2 Dec 2025

Abstract

Neuraminidase (NA) decorates the surface of the influenza virus, exerting a sialidase activity that enables the viral particle to be released in the host cell. Numerous sialic-based antiviral agents competitively bind to the NA cavity and are marketed worldwide for the treatment of [...] Read more.

Neuraminidase (NA) decorates the surface of the influenza virus, exerting a sialidase activity that enables the viral particle to be released in the host cell. Numerous sialic-based antiviral agents competitively bind to the NA cavity and are marketed worldwide for the treatment of Influenza A infection. We designed and validated a structure-based pharmacophore model for influenza neuraminidase (NA), which guided a virtual screening campaign against an in-house library of compounds already available for testing. This fast and cost-effective in silico strategy resulted in the identification of seven candidates possessing indole or isoquinoline chemical core. In vitro assays confirmed their favorable cytotoxicity profiles and identified only one, the 1-(1H-indol-3-ylcarbonyl)-3-piperidinecarboxylic acid (1), with reproducible inhibitory activity toward NA at non-cytotoxic concentrations. This work suggested a validated workflow for the discovery of novel NA inhibitors and highlighted an indole-based hit compound as a starting point for further optimization. Full article

(This article belongs to the Special Issue Enzyme Inhibitors: Design, Synthesis and Biological Evaluation—3rd Edition)

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13 pages, 4473 KB

Open AccessArticle

Rapid, Room-Temperature Synthesis of a Porous Organic Polymer for Highly Effective Removal of Trace Hg(II) from Water

by Shucai Gao, Libin Wan, Fayun Wang, Haidong Gao, Fanghui Zhao, Na Li, Jingjing Yao, Yeru Liu and Hongwei Liu

Molecules 2025, 30(23), 4635; https://doi.org/10.3390/molecules30234635 (registering DOI) - 2 Dec 2025

Abstract

Exposure to Hg²⁺-contaminated water poses severe risks to human health. Porous organic polymers (POPs) are known for removing heavy metals efficiently. However, the rapid and simple preparation of POP with efficient and selective adsorption capacities remains challenging. Herein, an effective strategy [...] Read more.

Exposure to Hg²⁺-contaminated water poses severe risks to human health. Porous organic polymers (POPs) are known for removing heavy metals efficiently. However, the rapid and simple preparation of POP with efficient and selective adsorption capacities remains challenging. Herein, an effective strategy for the room-temperature preparation of TpPa-1 via a 1-step Schiff-base reaction of 2,4,6-triformylphloroglucinol (Tp) and p-phenylenediamine (Pa-1) using scandium(III) trifluromethanesulfonate as a catalyst is described. Various approaches were used to characterize TpPa-1, including SEM, TEM, XRD, FT-IR, NMR, BET, and TG analysis. TpPa-1 was applied to adsorb trace Hg²⁺ from aqueous solution, and its adsorption performance was assessed through batch adsorption experiments. The results indicated that over 94% of 100 μg L⁻¹ Hg²⁺ was removed within 90 min, with the isotherm and kinetics conforming to the Freundlich and the pseudo-second-order models, respectively. Combined with XPS analysis, the Hg²⁺ adsorption of TpPa-1 was primarily dominated by chelation, competitive, and electrostatic interactions between the carbonyl groups of TpPa-1 and Hg²⁺. Because of its benefits of facile synthesis, enhanced removal performance, good selectivity, and reusability, the prepared POP material has great potential for Hg²⁺ removal from aqueous solutions. Full article

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28 pages, 14376 KB

Open AccessArticle

Theoretical Investigation of Structural and Optical Peculiarities of Bikaverin Fungal Pigment in Chloroform Solution

by Anastasia Povolotckaia, Dmitrii Pankin, Sergey Belousov, Andrey Boyko, Sergey Akulov, Evgenii Borisov, Anatoliy Gulyaev, Sergey Gudkov, Andrey Izmailov and Maxim Moskovskiy

Molecules 2025, 30(23), 4634; https://doi.org/10.3390/molecules30234634 (registering DOI) - 2 Dec 2025

Abstract

Bikaverin is a polyketide pigment metabolite produced by certain Fusarium genus fungi. It has a number of promising applications due to its biological properties, including a cytotoxic effect against certain cancer cell lines, antioomycete and nematicidal biological activity, and potential antiviral activity. A [...] Read more.

Bikaverin is a polyketide pigment metabolite produced by certain Fusarium genus fungi. It has a number of promising applications due to its biological properties, including a cytotoxic effect against certain cancer cell lines, antioomycete and nematicidal biological activity, and potential antiviral activity. A more accurate structural characterization using quantum chemical calculation methods may facilitate the study of other useful biological properties. Therefore, in this study, a single-molecule density functional theory study of bikaverin in chloroform solvent was conducted. In addition to the lowest state, two rotational conformers with energies higher by 0.74 and 0.32 kcal/mol were found, as well as the presence of a stable low-energy tautomeric state higher in energy by 1 kcal/mol. IR absorption spectra and UV-visible electronic absorption spectra were modeled for certain states. The attribution of the observed spectral peculiarities was performed. Vibrational modes and peaks sensitive to structural peculiarities were proposed for the IR absorption spectra of various energy states. The results obtained can be used to further control the structure of bikaverin and its derivatives. Full article

(This article belongs to the Section Molecular Structure)

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25 pages, 3646 KB

Open AccessArticle

SERAAK2 as a Serotonin Receptor Ligand: Structural and Pharmacological In Vitro and In Vivo Evaluation

by Agnieszka A. Kaczor, Agata Zięba, Tadeusz Karcz, Michał K. Jastrzębski, Katarzyna Szczepańska, Tuomo Laitinen, Marián Castro and Ewa Kędzierska

Molecules 2025, 30(23), 4633; https://doi.org/10.3390/molecules30234633 (registering DOI) - 2 Dec 2025

Abstract

Serotonin receptors, in particular 5-HT_1A and 5-HT_2A receptors, are important molecular targets for the central nervous system (CNS) disorders, such as schizophrenia, depression, anxiety disorders, memory deficits, and many others. Here, we present structural and pharmacological evaluation of a serotonin receptor [...] Read more.

Serotonin receptors, in particular 5-HT_1A and 5-HT_2A receptors, are important molecular targets for the central nervous system (CNS) disorders, such as schizophrenia, depression, anxiety disorders, memory deficits, and many others. Here, we present structural and pharmacological evaluation of a serotonin receptor ligand, SERAAK2, identified in a structure-based virtual screening campaign. Molecular docking studies revealed that SERAAK2 binds with its molecular targets via Asp3.32 as the main anchoring point, which is typical for orthosteric ligands of aminergic GPCRs. Molecular dynamics simulations confirmed the stability of the ligand binding poses in the studied receptors. MMGBSA calculations were in accordance with the receptor in vitro binding affinity studies, which indicated that SERAAK2 is a potent ligand of 5-HT_1A and 5-HT_2A receptors. It was also found that SERAAK2 displays favorable ADMET parameters. The demonstrated anxiolytic- and antidepressant-like effects of SERAAK2 in animal models, which may involve its interaction with 5-HT_1A receptors, warrant further studies to confirm these activities and elucidate the underlying mechanisms. Full article

(This article belongs to the Special Issue Hot Trends in Computational Drug Design)

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14 pages, 3211 KB

Open AccessArticle

Enhancement of the Antioxidant Activity of Hedysari Radix Particle Dispersion via ZIF-8/PEG Surface Co-Adsorption

by Xionggao Han, Chaoyue Wang, Jianmei Wang, Qiqi Pan, Jinghui Feng and Guanglei Zuo

Molecules 2025, 30(23), 4632; https://doi.org/10.3390/molecules30234632 (registering DOI) - 2 Dec 2025

Abstract

Herein, a co-adsorption modification based on ZIF-8 was introduced with the contribution of polyethylene glycol package to enhance the antioxidant potency of the Hedysari Radix disperse particles. In the solution system containing ethanol, the rough surface of the original Hedysari Radix disperse particles [...] Read more.

Herein, a co-adsorption modification based on ZIF-8 was introduced with the contribution of polyethylene glycol package to enhance the antioxidant potency of the Hedysari Radix disperse particles. In the solution system containing ethanol, the rough surface of the original Hedysari Radix disperse particles was improved by the typical co-adsorption modification with ZIF-8 and further smoothed by the package. The co-adsorption modifications, including ZIF-8 only, polyethylene glycol only, and ZIF-8 with polyethylene glycol, were all studied in the solution system. In particular, the modification that combined both the polyethylene glycol package and a suitable amount of ZIF-8 achieved the most significant enhancement of the catalase activity as well as the total antioxidant capacity value. The obtained hit platform alleviated the oxidative stress upon Caenorhabditis elegans and extended the survival time. This work suggested that meaningful co-adsorption modification could improve the potency of medicinal plant resources. Full article

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20 pages, 3048 KB

Open AccessArticle

Dynamic Hormonal Networks in Flax During Fusarium oxysporum Infection and Their Regulation by Spermidine

by Beata Augustyniak, Ivan Petrik, Danuse Tarkowska, Marta Burgberger, Wioleta Wojtasik, Ondrej Novak and Anna Kulma

Molecules 2025, 30(23), 4631; https://doi.org/10.3390/molecules30234631 (registering DOI) - 2 Dec 2025

Abstract

Background: Flax (Linum usitatissimum L.) is an economically important crop that is highly susceptible to Fusarium oxysporum f. sp. lini (Foln). While phytohormones are key regulators of defence, their interaction with polyamines during infection remains poorly understood. This study aimed to characterise [...] Read more.

Background: Flax (Linum usitatissimum L.) is an economically important crop that is highly susceptible to Fusarium oxysporum f. sp. lini (Foln). While phytohormones are key regulators of defence, their interaction with polyamines during infection remains poorly understood. This study aimed to characterise hormonal dynamics in flax under Foln infection and the modulatory role of spermidine (Spd). Methods: Targeted UPLC–MS/MS profiling quantified over 30 hormone-related compounds, including auxins, cytokinins, gibberellins, jasmonates, salicylic acid, and abscisic acid, in shoots and roots of healthy, infected, and Spd-treated plants. Two Spd concentrations (10 and 100 mM) were applied under controlled in vitro conditions. Results: Foln infection triggered tissue- and time-specific hormonal shifts, with early activation of jasmonate and auxin metabolism in shoots and later accumulation of salicylic acid and gibberellins in roots. Spd, particularly at 10 mM, reshaped these responses by reinforcing cytokinin and salicylic acid responses, stabilising auxin homeostasis, and enhancing jasmonate and abscisic acid responses. Conclusions: Spermidine coordinates hormone crosstalk, enabling balanced and efficient defence activation. The results highlight its potential as a priming agent enhancing flax resilience to F. oxysporum. Full article

(This article belongs to the Section Chemical Biology)

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33 pages, 3012 KB

Open AccessReview

β-Blockers in the Environment: Challenges in Understanding Their Persistence and Ecological Impact

by Anna Dzionek

Molecules 2025, 30(23), 4630; https://doi.org/10.3390/molecules30234630 (registering DOI) - 2 Dec 2025

Abstract

β-blockers are among the most highly consumed cardiovascular drugs worldwide, resulting in their classification as persistent and bioactive pharmaceutical pollutants. This review provides a mechanistically oriented synthesis of their environmental release, stereochemical and matrix-dependent transformation, biotic and abiotic degradation, and the ecotoxicological significance [...] Read more.

β-blockers are among the most highly consumed cardiovascular drugs worldwide, resulting in their classification as persistent and bioactive pharmaceutical pollutants. This review provides a mechanistically oriented synthesis of their environmental release, stereochemical and matrix-dependent transformation, biotic and abiotic degradation, and the ecotoxicological significance of their degradation products. Wastewater treatment plants are identified as the primary, yet variably efficient, emission sources to aquatic systems. Molecular structure, chirality, and interactions with environmental matrices are highlighted as key factors influencing transformation behaviour and residue persistence. Current evidence indicates that β-blockers and several transformation products retain pharmacological activity, driving organism- and community-level effects at environmentally relevant exposures. Major limitations in the field stem from methodological heterogeneity and uneven regional and temporal coverage, which continue to weaken long-term risk evaluation. By unifying analytical chemistry, pharmacological mechanistics, and environmental toxicology evidence, this review advances the narrative from descriptive occurrence reports toward systematic evaluation of transformation product persistence, mechanism-dependent residue stability, and their ecological implications. Full article

(This article belongs to the Special Issue Pharmaceuticals in the Environment: Micropollutants and Degradation Dynamics)

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15 pages, 2486 KB

Open AccessArticle

A New Diterpene with Cytotoxic Potential Against Human Tumor Cells

by Orfa Inés Contreras-Martínez, Briana Alarcón Avilés, Fillipe Vieira Rocha, Karine Zanotti, Tamara Teixeira, Jesus Sierra Martínez and Alberto Angulo-Ortíz

Molecules 2025, 30(23), 4629; https://doi.org/10.3390/molecules30234629 (registering DOI) - 2 Dec 2025

Abstract

Cancer is one of the most feared diseases in the world. Its incidence has increased steadily in recent years; it represents a significant burden of disease and is among the leading causes of death globally. Consequently, the search for novel compounds that serve [...] Read more.

Cancer is one of the most feared diseases in the world. Its incidence has increased steadily in recent years; it represents a significant burden of disease and is among the leading causes of death globally. Consequently, the search for novel compounds that serve as potential candidates for pharmacotherapeutic options and that can be used as treatments or adjuvants to control this disease is urgent. In this context, plant-derived phenolic diterpenes have shown antitumor activity against several types of cancer, inhibiting DNA synthesis, lipid metabolism, and bioenergetics of these cells, among other mechanisms, making these compounds an excellent alternative to continue investigating. The objective of this research was to evaluate the action of the previously undescribed natural diterpene 3,3′-diisopropyl-2,2′,5,5′-tetramethoxy-6,6′-dimethylbiphenyl-4,4′-diol (biisoespintanolcompound 2), against several human tumor cell lines (A549, MDA-MB-231, DU145, A2780, A2780-cis) and the non-tumor cell line MRC-5. Experiments with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and fluorescence with propidium iodide (PI), 4′,6-diamidino-2-phenylindole dilactate (DAPI), and green plasma revealed the cytotoxicity of 2 against these cells. Furthermore, morphological and chromogenic studies demonstrated the action of 2 on cell morphology and its inhibitory capacity of reproductive viability for colony formation in A549 cells. Furthermore, 3D experiments validated the damage caused by this diterpene in these cells. These results contribute to the search for novel compounds with antitumor potential and serve as a basis for advancing studies into the mechanisms of action of these compounds and the development of synthetic derivatives or analogs with a better antitumor profile. Full article

(This article belongs to the Special Issue Extraction and Analysis of New Bioactive Compounds Derived from Natural Products, 2nd Edition)

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13 pages, 12398 KB

Open AccessArticle

Synergistic Zn/Al Co-Doping and Sodium Enrichment Enable Reversible Phase Transitions in High-Performance Layered Sodium Cathodes

by Yaru Qin, Tingfei Yang, Na Chen, Jiale Li, Anqi Li, Yu Miao, Chenglong Shi, Jianmin Ma and Xue Qin

Molecules 2025, 30(23), 4628; https://doi.org/10.3390/molecules30234628 (registering DOI) - 2 Dec 2025

Abstract

Layered transition-metal oxides are among the most promising sodium-ion battery cathodes owing to their high specific capacities and structurally tunable frameworks. However, the prototypical P2-Na_0.67Ni_0.33Mn_0.67O₂ (NM) undergoes an irreversible P2 → O2 phase transition at high [...] Read more.

Layered transition-metal oxides are among the most promising sodium-ion battery cathodes owing to their high specific capacities and structurally tunable frameworks. However, the prototypical P2-Na_0.67Ni_0.33Mn_0.67O₂ (NM) undergoes an irreversible P2 → O2 phase transition at high voltages, accompanied by severe lattice strain and capacity fade, which hinders practical deployment. Here, we propose a cooperative regulation strategy that couples Zn/Al co-doping with Na enrichment, and successfully synthesize P2-Na_0.80Ni_0.14Zn_0.14Mn_0.58Al_0.14O₂ (NMZA-N14). The optimized NMZA-N14 delivers an initial discharge capacity of 125 mAh g⁻¹ at 0.1C and demonstrates exceptional cycling and rate performance, retaining 98.6% of its capacity after 100 cycles at 0.2C and 93.6% after 200 cycles at 1C. Kinetic analyses indicate a higher Na⁺ diffusion coefficient and a lower charge-transfer resistance in NMZA-N14, evidencing substantially accelerated ion transport. In situ X-ray diffraction further reveals a reversible P2 → OP4 phase transition in the high-voltage regime with a unit-cell volume change of only ~2.27%, thereby avoiding the irreversible structural degradation observed in NM. This synergistic modulation markedly enhances structural stability and electrochemical kinetics, providing a viable pathway for the rational design of high-performance sodium-ion battery cathodes. Full article

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20 pages, 2092 KB

Open AccessArticle

Hetero Diels–Alder Cycloaddition of Siloxy Vinylallenes—Synthesis of the Indolizidine Skeleton: Experimental and Computational Studies

by Juan Francisco Rodríguez-Caro, Gabriel Vargas-Arana, María del Mar Afonso and José Antonio Palenzuela

Molecules 2025, 30(23), 4627; https://doi.org/10.3390/molecules30234627 (registering DOI) - 2 Dec 2025

Abstract

Vinylallenes have been used in Diels–Alder reactions with a variety of dienophiles. However, vinylallenes activated at the allenic part of the molecule have been reacted only with carbon–carbon double bonds. We prepared siloxy vinylallenes by the base-induced equilibrium of silyl-protected allyl-propargyl alcohols. We [...] Read more.

Vinylallenes have been used in Diels–Alder reactions with a variety of dienophiles. However, vinylallenes activated at the allenic part of the molecule have been reacted only with carbon–carbon double bonds. We prepared siloxy vinylallenes by the base-induced equilibrium of silyl-protected allyl-propargyl alcohols. We found that these systems react with imines to form cycloadducts with total regio and facial selectivity, but only moderate endo:exo selectivity. The cycloadducts obtained were transformed into indolizidine derivatives. The reaction was studied computationally using DFT and compared to the reaction of siloxydienes. It was found that the main difference between those systems is the higher nucleophilicity of the siloxydienes compared to the siloxy vinylallenes. Full article

(This article belongs to the Section Organic Chemistry)

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