Molecules

11 pages, 1142 KB

Open AccessArticle

Design and Characterization of a New Phenoxypyridine–Bipyridine-Based Tetradentate Pt(II) Complex Toward Stable Blue Phosphorescent Emitters

by Da-Gyung Lim, Ju-Hee Lim, Chan Hee Ryu, Kang Mun Lee and Youngjin Kang

Molecules 2026, 31(2), 373; https://doi.org/10.3390/molecules31020373 - 20 Jan 2026

Abstract

Although various phosphorescent organic light-emitting diodes (PhOLEDs) have been developed, their lifetimes remain shorter than those of fluorescent OLEDs. In this study, a novel Pt(II) complex featuring a tetradentate ligand composed of bipyridine and phenoxypyridine, referred to as LL-O, was synthesized and [...] Read more.

Although various phosphorescent organic light-emitting diodes (PhOLEDs) have been developed, their lifetimes remain shorter than those of fluorescent OLEDs. In this study, a novel Pt(II) complex featuring a tetradentate ligand composed of bipyridine and phenoxypyridine, referred to as LL-O, was synthesized and fully characterized to evaluate its potential as a dopant for PhOLEDs. Geometry-optimized calculations indicate that LL-O adopts a distorted square–planar structure around the Pt(II) center. The complex displays bluish-green emission with maxima at 490 and 518 nm. However, it exhibits a low photoluminescence quantum yield (4%), primarily due to a dominant non-radiative decay rate that surpasses the radiative decay rate. Natural transition orbital analysis reveals that the emission of LL-O originates from a combination of triplet ligand-centered (³LC), triplet ligand-to-ligand charge-transfer (³LL′CT), and triplet metal-to-ligand charge-transfer (³MLCT) transitions. This compound also demonstrates high thermal stability (decomposition temperature > 340 °C) and an appropriate HOMO energy level (−5.58 eV), making it suitable for use as a dopant in versatile PhOLEDs. Full article

(This article belongs to the Special Issue Metal Complexes for Optical and Electronics Applications)

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12 pages, 1583 KB

Open AccessArticle

Interaction of Lysozyme with Sulfated β-Cyclodextrin: Dissecting Salt and Hydration Contributions

by Jacek J. Walkowiak

Molecules 2026, 31(2), 372; https://doi.org/10.3390/molecules31020372 - 20 Jan 2026

Abstract

This article investigates the thermodynamic driving force of the interaction between lysozyme (Lys) and sulfated β-cyclodextrin (β-CDS), with a particular emphasis on the elusive role of hydration during polyelectrolyte–protein binding. Using isothermal titration calorimetry (ITC), the binding affinity was quantified across varying temperatures [...] Read more.

This article investigates the thermodynamic driving force of the interaction between lysozyme (Lys) and sulfated β-cyclodextrin (β-CDS), with a particular emphasis on the elusive role of hydration during polyelectrolyte–protein binding. Using isothermal titration calorimetry (ITC), the binding affinity was quantified across varying temperatures and salt concentrations, employing a recently developed thermodynamic framework that explicitly separates the contributions from counterion release and hydration effects. The study reveals that while counterion release is minimal in the Lys/β-CDS system, hydration effects become a dominant factor influencing the binding free energy ΔG_b, especially as experimental temperature deviates from the characteristic temperature T₀. It demonstrates that hydration contributions can substantially weaken binding at increased salt concentration c_s. The high characteristic temperature T₀ and the salt-dependent heat capacity change indicate a complex interplay of water structure and ion association—significantly departing from commonly linear interpretations of ΔG_b vs. log c_s based solely on counterion release effects. This work advances the understanding of polyelectrolyte–protein interactions by providing the first direct quantification of the hydration effect in such complexes and may have an impact on the rational design of biomolecular assemblies and therapeutic carriers. Full article

(This article belongs to the Special Issue Supramolecular Host/Guest Compounds and Their Prospects for Multifunctional Materials)

17 pages, 980 KB

Open AccessArticle

Dose-Dependent Effects of Pear (Pyrus communis L.) Juice on Kombucha Polyphenols, Antioxidant Capacity, and Enzyme Inhibition

by Agata Kuraj and Joanna Kolniak-Ostek

Molecules 2026, 31(2), 371; https://doi.org/10.3390/molecules31020371 - 20 Jan 2026

Abstract

This study investigated the dose-dependent impact of pear juice supplementation on the chemical composition, phenolic profile, and biological activity of kombucha during 14 days of fermentation. Four formulations (0–75% pear juice) were evaluated for changes in (poly)phenols, organic acids, antioxidant capacity, and enzyme [...] Read more.

This study investigated the dose-dependent impact of pear juice supplementation on the chemical composition, phenolic profile, and biological activity of kombucha during 14 days of fermentation. Four formulations (0–75% pear juice) were evaluated for changes in (poly)phenols, organic acids, antioxidant capacity, and enzyme inhibition. UPLC-QToF-MS analysis demonstrated substantial remodeling of the phenolic profile in pear-enriched beverages, with marked increases in chlorogenic acid, arbutin, and flavonols. The total phenolic content increased proportionally with juice addition, reaching its highest level in the 75% juice formulation. Fermentation enhanced the antioxidant potential, with FRAP values more than doubling relative to the control. Pear supplementation also enhanced the inhibitory activity of key metabolic and neuroactive enzymes, including α-glucosidase, acetylcholinesterase, and butyrylcholinesterase. Principal component analysis linked phenolic enrichment to improved functional properties, highlighting the biochemical contribution of fruit-derived substrates to fermentation dynamics. Overall, the results demonstrate that pear juice acts as an effective bioactive modulator of kombucha fermentation, promoting the release, transformation, and accumulation of phenolic compounds and enhancing the antioxidant and enzyme-inhibitory potential of the beverage. These findings provide mechanistic insights into fruit-tea co-fermentation and support the development of phenolic-rich fermented beverages with improved nutritional quality and health benefits. Full article

(This article belongs to the Special Issue Potential of Natural Products as Drug Leads Possessing Antioxidant, Antiaging and Anticancer Properties)

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15 pages, 1631 KB

Open AccessArticle

Fragmentation Resilience Energy Mass Spectrometry (FREMS): Methods Validation and Compound Differentiation

by Alexander Yevdokimov, Kevin Colizza, James L. Smith and Jimmie C. Oxley

Molecules 2026, 31(2), 370; https://doi.org/10.3390/molecules31020370 - 20 Jan 2026

Abstract

Fragmentation Resilience Energy Mass Spectrometry (FREMS) builds on the field of energy-resolved mass spectrometry and previously used methods, e.g., Survival Yield. It exploits breakdown energies at near “continuous” ramp (0.2% NCE increments) to offer higher resolution and a reliable method for compound differentiation, [...] Read more.

Fragmentation Resilience Energy Mass Spectrometry (FREMS) builds on the field of energy-resolved mass spectrometry and previously used methods, e.g., Survival Yield. It exploits breakdown energies at near “continuous” ramp (0.2% NCE increments) to offer higher resolution and a reliable method for compound differentiation, contaminant identification and structural elucidation. Implementation of FREMS involves acquiring ion breakdown/formation curves as collision energy is incrementally increased. These curves themselves can be analyzed by several means to give a single metric—Fragmentation Resilience (FR₅₀). This value has been shown to be experimentally interchangeable with the modified-Survival Yield (m-SY₅₀) and the Cross-Intersect (C-I). A full panel of testing on an LTQ-Orbitrap revealed that breakdown energies depend only on three controllable parameters—number of ions inside the ion trap, Maximum Inject time and Activation Time. A fairly linear relationship (R² > 0.95) with proposed FR₅₀, m-SY₅₀ and C-I metrics provides reliable adjustment mechanisms for these variables via calibrations. Consequently, this technique can be applied to ions produced by any atmospheric pressure ionization processes and treated as exclusively in vacuo experiments. Applications of FREMS to 4-chlorobenzylpyridinium ion revealed that under collisional activated dissociation (CAD) conditions, the rate of decomposition of precursor ion is equivalent to the rate of formation of its fragments, i.e., normalized breakdown and formation curves intersect at inflection points. Full article

(This article belongs to the Special Issue Advances in the Mass Spectrometry of Chemical and Biological Samples)

17 pages, 2190 KB

Open AccessArticle

New Strategy Based on Click Reaction for Preparation of 3-Acyl-4-hydroxycoumarin-Modified Silica as a Perspective Material for the Separation of Rare Earth Elements

by Dzhamilya N. Konshina, Ekaterina S. Spesivaya, Ida A. Lupanova, Anton S. Mazur and Valery V. Konshin

Molecules 2026, 31(2), 369; https://doi.org/10.3390/molecules31020369 - 20 Jan 2026

Abstract

The separation of rare earth elements (REEs) with similar chemical properties remains a relevant challenge today, most often addressed using liquid–liquid and solid-phase extraction with various chelating agents. Excellent complexing agents for REEs are 1,3-diketones and their analogs. We have for the first [...] Read more.

The separation of rare earth elements (REEs) with similar chemical properties remains a relevant challenge today, most often addressed using liquid–liquid and solid-phase extraction with various chelating agents. Excellent complexing agents for REEs are 1,3-diketones and their analogs. We have for the first time proposed a method for preparing a material consisting of a covalently immobilized 3-acyl-4-hydroxycoumarin ligand on silica. For its synthesis, we employed a strategy based on the “click” reaction of 3-azidopropyl silica with a propargyl-containing coumarin–chalcone conjugate—this approach is the most tolerant and does not affect the coordinationally active fragment of the ligand. The material was characterized by thermal analysis, IR spectroscopy, and ¹³C NMR. The potential of the synthesized material for REE preconcentration was demonstrated at pH 5–5.5: high extraction efficiency for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III) was observed, with fast adsorption kinetics (30 min) and extraction degrees of ~98%. Under unified conditions of static and dynamic extraction for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III), affinity series toward the surface were obtained as a function of the distribution coefficient. It was shown that 10-fold molar excesses of Fe(III), Al(III), Cu(II), Ni(II), and Co(II) allow retention of more than 95% extraction for Dy(III) and Er(III). After adsorption of Dy(III) and Er(III), shifts in the carbonyl group absorption bands are visible in the IR spectra of the material, indicating a chelating mechanism of sorption. Additional studies are required for implementation in analytical and preparative REE separation schemes; however, preliminary data show that the material is a highly active adsorbent. Full article

(This article belongs to the Section Materials Chemistry)

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16 pages, 6138 KB

Open AccessArticle

Influence of Phlai (Zingiber montanum) and Njui (Bombax ceiba) Extracts in Bull Semen Extender on Antioxidant Activity and Sperm Quality

by Jiraporn Laoung-on, Nopparuj Outaitaveep, Jakree Jitjumnong, Sakaewan Ounjaijean and Kongsak Boonyapranai

Molecules 2026, 31(2), 368; https://doi.org/10.3390/molecules31020368 - 20 Jan 2026

Abstract

Infertility represents a significant global health issue, and the use of antioxidants in sperm preservation techniques provides an effective strategy to improve sperm quality. This study aims to examine the phytochemical components of Phlai and Njui extracts and their antioxidant effects on enhancing [...] Read more.

Infertility represents a significant global health issue, and the use of antioxidants in sperm preservation techniques provides an effective strategy to improve sperm quality. This study aims to examine the phytochemical components of Phlai and Njui extracts and their antioxidant effects on enhancing the motility of fresh bull semen. Among the extracts, Njui contained the highest levels of total phenolics, total tannins, and lycopene contents along with the strongest DPPH, ABTS, and AOPP inhibition. Phlai contained the highest levels of total flavonoids. Njui and combined extracts showed the strongest AGE inhibition. The motility of sperm in the semen extender supplemented with Phlai, Njui, and their combination exhibited greater total motility, particularly progressive motility, compared to sperm in the normal extender after 48–72 h. Furthermore, there was a reduced generation of ROS compared to sperm in the normal extender and with vitamin E acetate supplementation after 24–72 h. In conclusion, Phlai and Njui extracts, plentiful in bioactive chemicals, showed significant antioxidant activity and enhanced sperm motility by neutralizing free radicals and strengthening antioxidant defenses. The findings indicate that Phlai and Njui, especially in combination, provide advantages for sperm preservation. Full article

(This article belongs to the Special Issue Bioactive Compounds in Plants: Extraction and Application)

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38 pages, 2415 KB

Open AccessReview

Mulberry Leaf-Derived Bioactive Constituents on Diabetes: Structure, Extraction, Quality Analysis, and Hypoglycemic Mechanisms

by Siyue Zhou, Yidong Xu, Yehao Lin, Junyu Liu, Min Zhang, Joseph Buhagiar and Haixia Chen

Molecules 2026, 31(2), 367; https://doi.org/10.3390/molecules31020367 - 20 Jan 2026

Abstract

(1) Background: Diabetes mellitus is a chronic metabolic disease with a rising global prevalence. Mulberry leaf (ML), a traditional medicinal and edible plant, possesses notable hypoglycemic effects and has a long history of usage. This review aims to systematically consolidate the research progress [...] Read more.

(1) Background: Diabetes mellitus is a chronic metabolic disease with a rising global prevalence. Mulberry leaf (ML), a traditional medicinal and edible plant, possesses notable hypoglycemic effects and has a long history of usage. This review aims to systematically consolidate the research progress on the hypoglycemic constituents derived from ML, including their chemical structure, extraction methods, quality analysis techniques, and hypoglycemic mechanisms. (2) Methods: Adhering to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines, a comprehensive literature search was conducted using Web of Science and PubMed databases to find relevant studies published between 2015 and 2025. (3) Results: This review evaluates both conventional and modern techniques such as water extraction, ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and enzyme-assisted extraction (EAE), highlighting their advantages and limitations when applied on ML. Additionally, this review examines the analytical techniques applied in the quality control of ML and its constituents. This is complemented by a summary of hypoglycemic mechanisms, focusing on the inhibition of oxidative stress, amelioration of insulin resistance, regulation of related enzyme activity, and modulation of gut microbiota. (4) Conclusions: ML demonstrates considerable potential for treating diabetes. However, further studies are needed for new drug discovery based on new ML-derived bioactive constituents, highly efficient extraction methods, quality analysis techniques, and underlying mechanisms. Full article

(This article belongs to the Special Issue Extraction and Analysis of Natural Products in Food—3rd Edition)

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23 pages, 11750 KB

Open AccessArticle

Computational Identification of Blood–Brain Barrier-Permeant Microbiome Metabolites with Binding Affinity to Neurotransmitter Receptors in Neurodevelopmental Disorders

by Ricardo E. Buendia-Corona, María Fernanda Velasco Dey, Lisset Valencia Robles, Hannia Josselín Hernández-Biviano, Cristina Hermosillo-Abundis and Lucila Isabel Castro-Pastrana

Molecules 2026, 31(2), 366; https://doi.org/10.3390/molecules31020366 - 20 Jan 2026

Abstract

The gut microbiome produces thousands of metabolites with potential to modulate central nervous system function through peripheral or direct neural mechanisms. Tourette syndrome, attention-deficit/hyperactivity disorder, and autism spectrum disorder exhibit shared neurotransmitter dysregulation and microbiome alterations, yet mechanistic links between microbial metabolites and [...] Read more.

The gut microbiome produces thousands of metabolites with potential to modulate central nervous system function through peripheral or direct neural mechanisms. Tourette syndrome, attention-deficit/hyperactivity disorder, and autism spectrum disorder exhibit shared neurotransmitter dysregulation and microbiome alterations, yet mechanistic links between microbial metabolites and receptor-mediated neuromodulation remain unclear. We screened 27,642 microbiome SMILES metabolites for blood–brain barrier permeability using rule-based SwissADME classification and a PyTorch 2.0 neural network trained on 7807 experimental compounds (test accuracy 86.2%, AUC 0.912). SwissADME identified 1696 BBB-crossing metabolites following Lipinski’s criteria, while PyTorch classified 2484 metabolites with expanded physicochemical diversity. Following 3D conformational optimization (from SMILES) and curation based on ≤32 rotatable bonds, molecular docking was performed against five neurotransmitter receptors representing ionotropic (GABRA2, GRIA2, GRIN2B) and metabotropic (DRD4, HTR1A) receptor classes. The top 50 ligands across five receptors demonstrated method-specific BBB classification (44% SwissADME-only, 44% PyTorch-only, 12% overlap), validating complementary prediction approaches. Fungal metabolites from Ascomycota dominated high-affinity top ligands (66%) and menaquinone MK-7 showed broad phylogenetic conservation (71.4% of phylum). Our results establish detailed receptor–metabolite interaction maps, with fungal metabolites dominating high-affinity ligands, challenging the prevailing bacterial focus of the microbiome and providing a foundation for precision medicine and a framework for developing microbiome-targeted therapeutics to address clinical needs in neurodevelopmental disorders. Full article

(This article belongs to the Special Issue Molecular Docking in Drug Discovery, 2nd Edition)

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20 pages, 1685 KB

Open AccessArticle

Nutritional and Antioxidant Profile of Brown Eragrostis tef (Zucc.) Trotter Flour in Blends with Glycine max (L.) Merr. Flour

by Shewangzaw Addisu Mekuria, Kamil Czwartkowski and Joanna Harasym

Molecules 2026, 31(2), 365; https://doi.org/10.3390/molecules31020365 - 20 Jan 2026

Abstract

The still-growing demand for nutritious gluten-free products necessitates the development of a composite flour that addresses the nutritional deficiencies common in conventional gluten-free formulations. This study aimed to comprehensively characterize brown teff (Eragrostis tef (Zucc.) Trotter) and soybean (Glycine max (L.) [...] Read more.

The still-growing demand for nutritious gluten-free products necessitates the development of a composite flour that addresses the nutritional deficiencies common in conventional gluten-free formulations. This study aimed to comprehensively characterize brown teff (Eragrostis tef (Zucc.) Trotter) and soybean (Glycine max (L.) Merr.) composite flours at 0%, 10%, 20%, 30%, and 40% soybean inclusion levels (w/w) to establish evidence-based formulation guidelines for future products. Proximate composition, antioxidant properties (total polyphenol content—TPC, antioxidant capacity vs. 2,2-diphenyl-1-picrylhydrazyl radical—DPPH and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical—ABTS, ferric reducing antioxidant power—FRAP), particle size distribution, pasting properties, color characteristics, and molecular fingerprints (Fourier transform infrared spectroscopy—FTIR) were evaluated. A principal component analysis (PCA) was employed to identify compositional–functional relationships. Soybean inclusion significantly enhanced protein content from 9.93% (pure teff) to 23.07% (60:40 blend, dry matter), fat from 2.14% to 10.47%, and fiber from 3.43% to 6.72%. The antioxidant capacity increased proportionally with soybean content, with a 40% inclusion yielding FRAP values of 5.19 mg FeSO₄/g DM and TPC of 3.44 mg GAE/g DM. However, pasting viscosity decreased notably from 12,198.00 mPa·s (pure teff) to 129.00 mPa·s (60:40 blend), indicating a reduced gel-forming capacity caused by soybean addition. PCA revealed that nutritional composition (PC1: 70.6% variance) and pasting properties (PC2: 21.0% variance) vary independently, suggesting non-additive functional behavior in blends. Brown teff–soybean blends at a 20–30% soybean inclusion optimize the balance between protein enhancement, antioxidant preservation, and the maintenance of functional properties suitable for traditional applications, providing a nutritionally superior alternative for gluten-free product development. Full article

(This article belongs to the Special Issue Plant-Based Food Science: Chemical Composition and Biological Activity—2nd Edition)

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17 pages, 5589 KB

Open AccessReview

Construction and Advanced Utilization of Self-Assembled and Scale-Down Chitin Nanofibers for Polymer Composite Design

by Masayasu Totani and Jun-ichi Kadokawa

Molecules 2026, 31(2), 364; https://doi.org/10.3390/molecules31020364 - 20 Jan 2026

Abstract

This review provides a comprehensive overview of recent progress in chitin-based nanomaterials and their composite engineering. Particular focus is placed on techniques for constructing self-assembled chitin nanofibers (ChNFs) with tightly bundled fibrillar structures, as well as strategies for fabricating composites in which the [...] Read more.

This review provides a comprehensive overview of recent progress in chitin-based nanomaterials and their composite engineering. Particular focus is placed on techniques for constructing self-assembled chitin nanofibers (ChNFs) with tightly bundled fibrillar structures, as well as strategies for fabricating composites in which the ChNFs serve as reinforcing components, combined with natural polymeric matrices. In addition, high-crystalline scaled-down (SD-)ChNFs were fabricated through partial deacetylation of the ChNFs, followed by electrostatic repulsive disassembly of the abovementioned bundled fibrils in aqueous acetic acid, which were further used to reinforce composites comprising the other polysaccharides. Mixing the SD-ChNFs with low-crystalline chitin substrates further enabled the fabrication of all-chitin composites (AChCs) that exploit crystallinity contrast to achieve enhanced tensile strength. Moreover, the AChC films exhibited high cell-adhesive properties and promoted the formation of three-dimensional cell-networks, highlighting their potential for biomedical applications. Full article

(This article belongs to the Special Issue Polymeric Systems Loaded with Natural Bioactive Compounds, 2nd Edition)

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28 pages, 7303 KB

Open AccessArticle

Influence of Filler in the Form of Waste Wood Flour and Microcellulose on the Mechanical, Thermal, and Morphological Characteristics of Hierarchical Epoxy Composites

by Anna Sienkiewicz and Piotr Czub

Molecules 2026, 31(2), 363; https://doi.org/10.3390/molecules31020363 - 20 Jan 2026

Abstract

In response to growing interest in green additives derived from natural raw materials or post-production waste of natural origin, epoxy compositions containing the additive in the form of waste wood flour and microcellulose were prepared. The research involved the chemical modification of the [...] Read more.

In response to growing interest in green additives derived from natural raw materials or post-production waste of natural origin, epoxy compositions containing the additive in the form of waste wood flour and microcellulose were prepared. The research involved the chemical modification of the additive through a two-stage silanization process using 3-aminopropyltriethoxysilane. Followed by filler’s characterization using Fourier Transformed Infrared Spectroscopy (FT-IR) to analyze the modification in chemical structure, Wide Angle X-Ray Diffraction (WAXD) to detect differences in crystal structure, and Scanning Electron Microscopy (SEM) to observe morphological changes. Next, waste oak flour (WF) and microcrystalline cellulose (MCC) were used in unmodified and silanized form (sil-WF and sil-MCC, respectively) to prepare epoxy composites, followed by testing their influence on the mechanical (hardness, tensile strength, flexural strength, compressive strength, and impact strength), thermal, and morphological characteristics of epoxy composites based on Epidian 6. Comparing the effect of modification on the properties of the analyzed additives, it was found that silanization had a larger impact on increasing the interaction of the waste wood flour with the epoxy matrix than silanization of MCC due to a lesser tendency of the sil-WF than the sil-MCC to agglomerate. An enhanced interaction of sil-WF with the polymer resulted in improved mechanical properties. Composite EP/sil-WF (cured epoxy composite based on low-molecular-weight epoxy resin Epidian 6 filled with 5 wt.% of silanized wood flour) was characterized by improved flexural (61.97 MPa) and compressive properties (69.1 MPa) compared to both EP/WF (cured epoxy composite based on low-molecular-weight epoxy resin Epidian 6 filled with 5 wt.% of unmodified wood flour) (42.39 MPa and 61.0 MPa) and the unfilled reference composition (54.55 MPa and 67.4 MPa, respectively). Moreover, compositions containing a cellulosic additive were characterized by better impact properties than the reference composition. Full article

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22 pages, 2527 KB

Open AccessArticle

Synthesis and Study of Substituted Chalcones Combined with Fluoroazobenzenes—New Photoswitches for Application in Biological Systems

by Piotr Tobiasz, Damian Mielecki, Anna Stachurska-Skrodzka, Jakub Miętus, Filip Borys and Hanna Krawczyk

Molecules 2026, 31(2), 362; https://doi.org/10.3390/molecules31020362 - 20 Jan 2026

Abstract

Chalcones have garnered significant research interest due to their various medical bioactivities. Several chalcone compounds have been approved for marketing and clinical use in the treatment of various diseases. A critical aspect of the action of chalcones is their effect on microtubules. They [...] Read more.

Chalcones have garnered significant research interest due to their various medical bioactivities. Several chalcone compounds have been approved for marketing and clinical use in the treatment of various diseases. A critical aspect of the action of chalcones is their effect on microtubules. They are considered an excellent target for chemotherapeutic agents for the treatment of cancer. Consequently, scientists are constantly developing novel chalcone drug agents and also innovative drug delivery strategies. In this manuscript, we report the first synthesis of 12 new visible-light-activated, photoswitchable chalcone-based microtubule inhibitors (17a–17l). Among the obtained compounds, one photoswitch demonstrated light-dependent cytotoxicity in the PC-3 cancer cell line. The IC₅₀ value of the Z conformer was determined to be 4.75 ± 1.00 μM after 48 h of treatment. The E conformer exhibited slightly lower activity compared to the Z conformer, with an IC₅₀ value of 5.80 ± 0.80 µM following 48 h of incubation. In this study, NMR and UV spectroscopy, along with computational methods, were employed. Full article

(This article belongs to the Special Issue Organic Molecules in Drug Discovery and Development)

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14 pages, 5529 KB

Open AccessArticle

BAM 15 Exerts Molluscicidal Effects on Pomacea canaliculata Through the Induction of Oxidative Stress, Impaired Energy Metabolism, and Tissue Damage

by Liping Wang, Haonan Yu, Guoli Qu, Jiankun Jin, Jie Wang and Yuntian Xing

Molecules 2026, 31(2), 361; https://doi.org/10.3390/molecules31020361 - 20 Jan 2026

Abstract

Background: The golden apple snail (Pomacea canaliculata), an invasive species originating from South America, has inflicted considerable agricultural and ecological harm in non-native habitats. While the molluscicide niclosamide is currently effective against P. canaliculata, its prolonged use raises environmental concerns [...] Read more.

Background: The golden apple snail (Pomacea canaliculata), an invasive species originating from South America, has inflicted considerable agricultural and ecological harm in non-native habitats. While the molluscicide niclosamide is currently effective against P. canaliculata, its prolonged use raises environmental concerns and the risk of resistance development. Results: BAM 15 possesses strong molluscicidal activity against P. canaliculata, with 72 h LC₅₀ values of 0.4564 mg/L for adults (shell height: 20–25 mm), 0.3352 mg/L for subadults (10–15 mm), and 0.1142 mg/L for juveniles (2–3 mm). Metabolomic and proteomic profiling revealed that the altered metabolites and proteins both converged on energy metabolism and oxidative stress. Experimental validation revealed that BAM15 collapsed the mitochondrial membrane potential, drove MDA and H₂O₂ upward while depleting NADPH, boosted CAT, SOD and GPX activities, yet suppressed GR, and ultimately inflicted overt damage in the head-foot tissue of P. canaliculata. Conclusions: Our findings reveal that BAM 15 operates via a three-stage mechanism: (1) it disrupts membrane potential (ΔΨm) and impairs ATP production, severely disturbing energy metabolism; (2) energy deficits stimulate excessive electron transport chain activity, generating reactive oxygen species (ROS) and initiating oxidative stress; (3) persistent metabolic imbalance and oxidative damage culminate in extensive tissue injury. These results identify BAM 15 as a promising candidate for molluscicide development. Full article

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65 pages, 861 KB

Open AccessReview

Fermented Plant-Based Foods and Postbiotics for Glycemic Control—Microbial Biotransformation of Phytochemicals

by Emilia Cevallos-Fernández, Elena Beltrán-Sinchiguano, Belén Jácome, Tatiana Quintana and Nadya Rivera

Molecules 2026, 31(2), 360; https://doi.org/10.3390/molecules31020360 - 20 Jan 2026

Abstract

Plant-based fermented foods are increasingly promoted for glycemic control, yet their mechanisms and clinical impact remain incompletely defined. This narrative review synthesizes mechanistic, preclinical, and human data for key matrices—kimchi and other fermented vegetables, tempeh/miso/natto, and related legume ferments, kombucha and fermented teas, [...] Read more.

Plant-based fermented foods are increasingly promoted for glycemic control, yet their mechanisms and clinical impact remain incompletely defined. This narrative review synthesizes mechanistic, preclinical, and human data for key matrices—kimchi and other fermented vegetables, tempeh/miso/natto, and related legume ferments, kombucha and fermented teas, plant-based kefir, and cereal/pulse sourdoughs. Across these systems, microbial β-glucosidases, esterases, tannases, and phenolic-acid decarboxylases remodel polyphenols toward more bioaccessible aglycones and phenolic acids, while lactic and acetic fermentations generate organic acids, exopolysaccharides, bacterial cellulose, γ-polyglutamic acid, γ-aminobutyric acid, and bioactive peptides. We map these postbiotic signatures onto proximal mechanisms—α-amylase/α-glucosidase inhibition, viscosity-driven slowing of starch digestion, gastric emptying and incretin signaling, intestinal-barrier reinforcement, and microbiota-dependent short-chain–fatty-acid and bile-acid pathways—and their downstream effects on AMPK/Nrf2 signaling and the gut–liver axis. Animal models consistently show improved glucose tolerance, insulin sensitivity, and hepatic steatosis under fermented vs. non-fermented diets. In humans, however, glycemic effects are modest and highly context-dependent: The most robust signal is early postprandial attenuation with γ-PGA-rich natto, strongly acidified or low-glycemic sourdough breads, and selected kombucha formulations, particularly in individuals with impaired glucose regulation. We identify major sources of heterogeneity (starters, process parameters, substrates, background diet) and safety considerations (sodium, ethanol, gastrointestinal symptoms) and propose minimum reporting standards and trial designs integrating metabolomics, microbiome, and host-omics. Overall, plant-based ferments appear best positioned as adjuncts within cardiometabolic dietary patterns and as candidates for “purpose-built” postbiotic products targeting early glycemic excursions and broader metabolic risk. Full article

(This article belongs to the Special Issue Phytochemistry, Antioxidants, and Anti-Diabetes)

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13 pages, 418 KB

Open AccessArticle

Synergistic Mechanisms and Comprehensive Functional Evaluation of Bioactive Components from Olive and Chinese Olive

by Hongyang Pan, Zhaojun Wang and Jie Chen

Molecules 2026, 31(2), 359; https://doi.org/10.3390/molecules31020359 - 20 Jan 2026

Abstract

Olive and Chinese olive are rich sources of bioactive compounds with reported sensory and hepatoprotective activities; however, the synergistic effect between their functional components have not been systematically evaluated. In this study, DF3 (functional fraction isolated from olive) and GF3 (functional fraction isolated [...] Read more.

Olive and Chinese olive are rich sources of bioactive compounds with reported sensory and hepatoprotective activities; however, the synergistic effect between their functional components have not been systematically evaluated. In this study, DF3 (functional fraction isolated from olive) and GF3 (functional fraction isolated from Chinese olive) were obtained using a combination of solvent extraction, supercritical fluid extraction, and polyamide column chromatography. To investigate potential synergistic effects, the two fractions were blended at different ratios (1:1, 2:1, and 1:2), and their taste-modulating properties, antioxidant capacity, and anti-intoxication and hepatoprotective activities were assessed using sensory analysis, radical scavenging assays, and biochemical indicators. Compared with the individual fractions, the blended formulations exhibited enhanced taste intensity, improved antioxidant capacity, and stronger hepatoprotective effects, as evidenced by greater reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Quantitative assessment using a combination index approach revealed a clear positive interaction between DF3 and GF3, with the GF3–DF3 (2:1) blend showing the most pronounced overall enhancement across multiple functional endpoints. Overall, this study provides a systematic and quantitative evaluation of synergistic effect between functional bioactive fractions and offers methodological guidance for the rational optimization of functional formulations. Full article

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19 pages, 1003 KB

Open AccessReview

Suzetrigine, a Na_V1.8 Inhibitor as a Novel Approach for Pain Therapy—A Medicinal and Chemical Drug Profile

by Rawan M. Medhat, Omnia A. Kotb and Daniel Baecker

Molecules 2026, 31(2), 358; https://doi.org/10.3390/molecules31020358 - 20 Jan 2026

Abstract

Suzetrigine was approved by the US American Food and Drug Administration in 2025 as the first oral, non-opioid, selective inhibitor of Na_V1.8 sodium channel for the treatment of acute pain. Therefore, it represents a groundbreaking advancement in pain management. This review [...] Read more.

Suzetrigine was approved by the US American Food and Drug Administration in 2025 as the first oral, non-opioid, selective inhibitor of Na_V1.8 sodium channel for the treatment of acute pain. Therefore, it represents a groundbreaking advancement in pain management. This review aims to provide an overview of the milestones in the medicinal-chemical development of Na_V1.8 inhibitors, eventually leading to suzetrigine. The multi-step synthesis route of suzetrigine is presented. Taking structural features into account, insights are provided into what plays a role for the inhibition of the Na_V1.8 channel. In addition, pharmacodynamic and pharmacokinetic aspects of the new drug, such as bioavailability, metabolism, and interaction with CYP450 enzymes, are discussed. A summary based on a large number of clinical trials demonstrating remarkable efficacy completes this comprehensive drug profile of suzetrigine, while also addressing limitations of the clinical trials and suggesting future perspectives. Full article

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

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25 pages, 4921 KB

Open AccessArticle

In Silico and In Vitro Insights into the Pharmacological Potential of Pouzolzia zeylanica

by Nguyen Anh Hung, Vu Thi Thu Le, Nguyen Viet Hung, Ha Thi Minh Tam, Nguyen Ngoc Linh, Nguyen Quang Hop, Nguyen Thi Hanh and Do Tien Lam

Molecules 2026, 31(2), 357; https://doi.org/10.3390/molecules31020357 - 20 Jan 2026

Abstract

The present study involves the isolation, structural elucidation, and biological evaluation of eight compounds from Pouzolzia zeylanica. From the n-hexane and ethyl acetate extracts of the plant, eight compounds were successfully isolated and identified: oleanolic acid (1), ursolic acid [...] Read more.

The present study involves the isolation, structural elucidation, and biological evaluation of eight compounds from Pouzolzia zeylanica. From the n-hexane and ethyl acetate extracts of the plant, eight compounds were successfully isolated and identified: oleanolic acid (1), ursolic acid (2), 2α-hydroxyursolic acid (3), 3β-O-acetyl-12-oleanen-28-oic acid (4), 5-hydroxy-6,7-dimethoxyflavanone (5), 4′-methoxytectochrysin (6), 3,4′,5,7-tetrahydroxyflavanone-3-O-L-rhamnopyranoside (7), and 3,3′,5,5′,7-pentahydroxyflavanone-3-O-L-rhamnopyranoside (8). These compounds were evaluated for in vitro antioxidant activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation inhibition (TBARS) assays, as well as anti-inflammatory activity via inhibition of nitric oxide (NO) production and the secretion of pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in RAW 264.7 macrophages. It was observed that compound 3 exhibited the strongest antioxidant activity with IC₅₀ values of 18.52 ± 1.50 µM (DPPH) and 10.34 ± 0.93 µM (TBARS), whereas compounds 2, 5, and 6 showed moderate to weak effects. Meanwhile, compound 8 demonstrated the most potent anti-inflammatory effect with IC₅₀ values of 16.25 ± 0.95 µM (NO inhibition), 12.97 ± 0.88 µM (TNF-α inhibition), and 22.52 ± 1.98 µM (IL-6 inhibition). Furthermore, in silico approaches were employed, including density functional theory (DFT) calculations to predict the antioxidant mechanisms of compounds 1 and 3 and molecular docking to assess the cyclooxygenase-2 (COX-2) and phosphodiesterase-4B (PDE4B) inhibitory potentials of compounds 4, 7, and 8. Computational results aligned well with experimental data, supporting the potential of these compounds as natural antioxidant and anti-inflammatory agents. Full article

(This article belongs to the Special Issue Bioactive Compounds in Plants: Extraction and Application)

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30 pages, 731 KB

Open AccessReview

Bacteriocins, a New Generation of Sustainable Alternatives to Antibacterial Agents in Primary Food Production Systems

by Besarion Meskhi, Svetoslav Dimitrov Todorov, Dmitry Rudoy, Anastasiya Olshevskaya, Victoria Shevchenko, Tatiana Maltseva, Arkady Mirzoyan, Denis Kozyrev, Mary Odabashyan, Svetlana Teplyakova and Maria Mazanko

Molecules 2026, 31(2), 356; https://doi.org/10.3390/molecules31020356 - 19 Jan 2026

Abstract

Modern agriculture faces the critical need to develop sustainable, safe, and effective strategies for enhancing productivity, protecting plants and animals, and ensuring food security. Challenges posed by antibiotic resistance and the adverse environmental and consumer health impacts of chemical agents are driving the [...] Read more.

Modern agriculture faces the critical need to develop sustainable, safe, and effective strategies for enhancing productivity, protecting plants and animals, and ensuring food security. Challenges posed by antibiotic resistance and the adverse environmental and consumer health impacts of chemical agents are driving the search for eco-friendly alternatives. In this context, bacteriocins—naturally occurring antimicrobial peptides synthesized by diverse bacteria—represent a promising alternative to traditional chemical compounds. This article reviews the potential and current advances in bacteriocin applications across agricultural sectors, with particular focus on their targeted antagonistic activity, structural diversity, commercial bacteriocin-based products, and their utilization in livestock farming, crop production, poultry farming, and aquaculture. Key findings demonstrate that bacteriocins, particularly nisin and pediocin PA-1, exhibit potent activity against major agricultural pathogens including Listeria monocytogenes, Staphylococcus aureus, Clostridium perfringens, and Escherichia coli, with efficacy rates reaching 90% in mastitis treatment and significantly reducing pathogen loads in poultry and aquaculture systems. Commercial products such as Nisaplin, Wipe Out, and ALTA 2431 have been successfully implemented in veterinary medicine and food production. In aquaculture, bacteriocins effectively control Lactococcus garvieae, Aeromonas spp., Vibrio spp., and Pseudomonas aeruginosa, contributing to sustainable disease management with minimal environmental impact. It can be suggested that bacteriocins may play an essential role in combating pathogens and offer viable alternatives to conventional antibiotics across primary food production systems, though optimization of production methods and regulatory frameworks remains essential for broader commercial adoption. Full article

(This article belongs to the Special Issue Green Chemistry and Molecular Tools in Agriculture)

28 pages, 697 KB

Open AccessReview

Triazole and Pyrazole Hybrids of Electrophilic Natural Products as Promising Anticancer Agents

by Alessia Da Fermo, Alessandra Bisi, Rebecca Orioli, Silvia Gobbi and Federica Belluti

Molecules 2026, 31(2), 355; https://doi.org/10.3390/molecules31020355 - 19 Jan 2026

Abstract

Naturally inspired electrophilic scaffolds, such as chalcone, curcumin, aurone, C-5-monocarbonyl-curcumin, and bis-(arylidene)piperidone, are considered privileged structures because of their ability to interact with a variety of biological macromolecules, including receptors and enzymes. They thus serve as versatile platforms for drug discovery efforts aimed [...] Read more.

Naturally inspired electrophilic scaffolds, such as chalcone, curcumin, aurone, C-5-monocarbonyl-curcumin, and bis-(arylidene)piperidone, are considered privileged structures because of their ability to interact with a variety of biological macromolecules, including receptors and enzymes. They thus serve as versatile platforms for drug discovery efforts aimed at developing structurally related analogues endowed with improved bioactivity. Five-membered nitrogen-based heterocycles, such as triazole and pyrazole, have been widely used in medicinal chemistry both as templates and spacers for the design of bioactive compounds; they indeed provide the advantage of enhancing favourable interactions with the target, while also improving solubility and bioavailability, along with reducing toxicity. This review reports the latest advances in the development of hybrids incorporating the above classes of synthons acting as potential anticancer chemotherapeutics and provides a critical summary of the design strategies that have guided the development of antitumor agents. Full article

(This article belongs to the Special Issue Heterocycles in Medicinal Chemistry III)

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