Molecules

21 pages, 6031 KB

Open AccessArticle

Erica spiculifolia Extract Potentiates Cisplatin Cytotoxicity by Reactivating p53 and Caspase-3-Dependent Apoptosis in Colorectal Carcinoma

by Rositsa Mihaylova, Nikolay Bebrivenski, Dimitrina Zheleva-Dimitrova, Rumyana Simeonova, Vesela Lozanova, Ralitza Alexova, Vanyo Mitev, Reneta Gevrenova and Georgi Momekov

Molecules 2026, 31(4), 710; https://doi.org/10.3390/molecules31040710 - 18 Feb 2026

Abstract

Resistance to apoptosis represents a major limitation of platinum-based chemotherapy in colorectal carcinoma, frequently arising from impaired p53 signaling and inefficient execution of programmed cell death. In this study, we investigated the anticancer activity of Erica spiculifolia extract (ESE) and its ability to [...] Read more.

Resistance to apoptosis represents a major limitation of platinum-based chemotherapy in colorectal carcinoma, frequently arising from impaired p53 signaling and inefficient execution of programmed cell death. In this study, we investigated the anticancer activity of Erica spiculifolia extract (ESE) and its ability to synergistically enhance cisplatin cytotoxicity in HT-29 colorectal carcinoma cells. Cell viability was assessed using the MTT assay, followed by formal combination analysis based on the Chou–Talalay methodology. Combination experiments employed a non-constant ratio regimen in which a fixed ESE concentration (45 µg/mL) was combined with serial cisplatin dilutions (45.0–2.8 µg/mL) to define interaction behavior across multiple effect levels. Quantitative analysis revealed a strong superadditive effect, with Combination Index values well below 1 and markedly elevated Dose Reduction Indices for cisplatin, indicating substantial dose-sparing across effect levels. To elucidate the molecular basis of this synergism, apoptosis-related protein expression was profiled using a membrane-based immunoassay. Combined ESE and cisplatin treatment induced full-scale p53 reactivation, including restoration of phosphorylated p53 isoforms associated with DNA damage-dependent apoptotic signaling. Acridine orange/propidium iodide staining confirmed a pronounced increase in early and late apoptotic/necrotic cells following combination treatment. UHPLC-HRMS analysis identified kaempferol 3-O-glucoside (8830.19 ± 11.01 ng/mg dw) and myricitrin (3074 ± 3.12 ng/mg) as predominant flavonols, followed by naringenin 7-O-glucoside (5958.96 ± 9.98 ng/mg), while chlorogenic, cinnamic, quinic, and gallic acids were the main phenolic acids detected. These constituents may contribute to HT-29 cell sensitization to cisplatin. Full article

(This article belongs to the Special Issue Functional Evaluation of Bioactive Compounds from Natural Sources, 2nd Edition)

► Show Figures

Figure 1

10 pages, 731 KB

Open AccessFeature PaperArticle

Eco-Friendly Synthesis of 2-Styryl-benzo[d][1,3]oxazin-4-ones from N-Cinnamoyl-Anthranilic Acids

by Armando Zarrelli and Luigi Longobardo

Molecules 2026, 31(4), 709; https://doi.org/10.3390/molecules31040709 - 18 Feb 2026

Abstract

N-cinnamoyl anthranilic acids are synthesized in a single, eco-friendly step by condensing various cinnamic acids with free 2-aminobenzoic acid derivatives using the mixed carbonic anhydride method. Subsequently, converting the resulting N-cinnamoyl anthranilic acids into their corresponding mixed carbonic anhydrides rapidly and [...] Read more.

N-cinnamoyl anthranilic acids are synthesized in a single, eco-friendly step by condensing various cinnamic acids with free 2-aminobenzoic acid derivatives using the mixed carbonic anhydride method. Subsequently, converting the resulting N-cinnamoyl anthranilic acids into their corresponding mixed carbonic anhydrides rapidly and efficiently affords 2-styryl-benzo[d][1,3]oxazin-4-ones. The method employs green solvents, such as acetone and 2-methyltetrahydrofuran; does not require metal catalysts or reflux conditions; and yields the desired final products without chromatographic purification. Full article

(This article belongs to the Special Issue Chemical Synthesis and Biological Activity of Aromatic Amino Acid Derivatives)

► Show Figures

Graphical abstract

18 pages, 5118 KB

Open AccessArticle

Enhanced Adsorption of Xylenol Orange by CTAB-Functionalized Tomato-Derived Biochar: Mechanisms and Performance Evaluation

by Shirui Zheng, Mengjie Bai, Yongwei Li, Runxiu He, Wenxu Wang, Yanping Feng, Haijie Wang, Fangfang Liu and Zhihao Fang

Molecules 2026, 31(4), 708; https://doi.org/10.3390/molecules31040708 - 18 Feb 2026

Abstract

In this work, a tomato biochar composite modified with cetyltrimethylammonium bromide (CTAB@TBC) was successfully synthesized using an ethanol solution method. It was comprehensively characterized to evaluate its morphology (SEM), crystal structure (XRD), chemical bonding (FT-IR and Raman spectroscopy), surface area (BET analysis), and [...] Read more.

In this work, a tomato biochar composite modified with cetyltrimethylammonium bromide (CTAB@TBC) was successfully synthesized using an ethanol solution method. It was comprehensively characterized to evaluate its morphology (SEM), crystal structure (XRD), chemical bonding (FT-IR and Raman spectroscopy), surface area (BET analysis), and thermal stability (TGA). The adsorption performance of the composite for xylenol orange (XO) was subsequently evaluated in detail. The findings revealed that CTAB@TBC exhibited a maximum adsorption capacity of 150.59 mg/g for XO. Kinetic analysis indicated that the adsorption process conformed to a pseudo-second-order model, implying that chemisorption was the step limiting the rate. The Langmuir model accurately described the adsorption isotherm data, suggesting monolayer adsorption on a uniform surface. Thermodynamic evaluation further revealed a negative Gibbs free energy (ΔG) change, confirming the spontaneity of the adsorption process. In summary, the results suggest that CTAB@TBC is a highly effective adsorbent for eliminating dyes from wastewater and offers considerable promise for treating industrial effluents. Full article

► Show Figures

Figure 1

21 pages, 1701 KB

Open AccessArticle

Steering of Crystal Cell Volumes in Apatites and Bioapatites

by Andrzej Kuczumow, Agnieszka Lasota, Mieczysław Gorzelak, Paulina Wojtyła-Buciora, Przemysław Biliński, Małgorzata Bernatek, Karolina Turżańska, Jan Olszewski, Przemysław Dyndor, Maciej Jarzębski, Marek Wieruszewski and Mirosław Jabłoński

Molecules 2026, 31(4), 707; https://doi.org/10.3390/molecules31040707 - 18 Feb 2026

Abstract

The biological variability of apatites in different hard tissues of organisms was the starting point for this investigation. Materials such as whale rostrums, ganoine, and some fish bones were analyzed. It has been proven that different organisms select specific kinds of apatites for [...] Read more.

The biological variability of apatites in different hard tissues of organisms was the starting point for this investigation. Materials such as whale rostrums, ganoine, and some fish bones were analyzed. It has been proven that different organisms select specific kinds of apatites for the construction of their hard organs at the level of the crystal cell. This probably results from the long-lasting adaptation of the construction to their environmental needs. The materials are characterized by the parameters Δd and ΔE, being the real and apparent deviations from Bragg’s dimension d and the energy of excitation in XRD—E. This study is based on previously published, verified results from a number of researchers and research groups. The derivation of expressions was possible due to an original approach to Bragg’s equation, finally finished in the reformulation of the law, which describes the interplay between the absolute value of the probing excitation energy E and the crystal cell’s internal volume V. It enabled the classification of apatite biomaterials in living and fossil organisms, as well as the classification of the apatite excretions. In addition, the following different possible modes of changes in Bragg’s dimension d were illustrated—spontaneous geometrical expansion, thermal action, pressurization, and single- and multiple-ion exchanges. The contributions of such expansions were estimated. We can steer the cell volume of apatites in various ways. It has been proven that the volume expansion is linearly coupled with the expansion of Bragg’s d parameter in the hexagonal system. Full article

► Show Figures

Figure 1

18 pages, 842 KB

Open AccessArticle

Original Synthesis of Substituted 6H-Benzo[c]chromene Derivatives Using a TDAE and Pd-Catalyzed Cyclization Strategy

by Donia Ben Salah, Omar Khoumeri, Theo-Bob Muller, Naceur Hamdi, Thierry Terme and Patrice Vanelle

Molecules 2026, 31(4), 706; https://doi.org/10.3390/molecules31040706 - 18 Feb 2026

Abstract

We report an efficient synthetic method for the preparation of 6H-benzo[c]chromenes from substituted 1-(2′-bromo-[1,1′-biphenyl]-2-yl)-2-phenylethanols. These intermediates were obtained via a TDAE-initiated reaction between new substituted 2′-bromo-[1,1′-biphenyl]-2-carbaldehyde derivatives and substituted nitrobenzylic chlorides. The second step involved a palladium-catalyzed intramolecular O-arylation [...] Read more.

We report an efficient synthetic method for the preparation of 6H-benzo[c]chromenes from substituted 1-(2′-bromo-[1,1′-biphenyl]-2-yl)-2-phenylethanols. These intermediates were obtained via a TDAE-initiated reaction between new substituted 2′-bromo-[1,1′-biphenyl]-2-carbaldehyde derivatives and substituted nitrobenzylic chlorides. The second step involved a palladium-catalyzed intramolecular O-arylation of the alcohol intermediate under microwave irradiation (110 °C for 1.5 h). The structure of 6H-benzo[c]chromene derivatives was confirmed by X-ray crystallography of product 5c. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

17 pages, 2571 KB

Open AccessArticle

Catalytic Performance of Flexible Polycationic Membrane Derived from Polyacrylonitrile for Advanced Applications

by Yue Gao, Xuan Qi and Junfeng Zhang

Molecules 2026, 31(4), 705; https://doi.org/10.3390/molecules31040705 - 18 Feb 2026

Abstract

A novel polycationic membrane (PCM) was synthesized by the cyclization of polyacrylonitrile (PAN) with m-ethylene diamine, converting the nitrile groups into pyridine units, followed by quaternization with 1-bromobutane. The resulting PCM was further functionalized by loading the photocatalyst, phosphomolybdic acid (PMo), via anion [...] Read more.

A novel polycationic membrane (PCM) was synthesized by the cyclization of polyacrylonitrile (PAN) with m-ethylene diamine, converting the nitrile groups into pyridine units, followed by quaternization with 1-bromobutane. The resulting PCM was further functionalized by loading the photocatalyst, phosphomolybdic acid (PMo), via anion exchange, forming a new type of photocatalytic material, PM-PCM. Under visible light irradiation, the PM-PCM photocatalyst achieved an impressive methylene blue degradation rate of 98%. Additionally, the nanofiber membrane morphology facilitates the efficient recovery of the catalyst, with 98% of the initial degradation efficiency maintained after five photocatalytic cycles. This robust, highly efficient, and recyclable material provides a new approach for catalyst support. To the best of our knowledge, PM-PCM is the first reported photocatalyst of this kind. This cost-effective, functionalized membrane material utilizes solar light as an economical and clean energy source, offering promising potential for sustainable environmental applications. Full article

(This article belongs to the Special Issue Green Chemistry in China: Advancing Sustainable Science for a Better World)

► Show Figures

Figure 1

24 pages, 31522 KB

Open AccessArticle

Fabrication and Detailed Characterization of PLA/PEG Composite Nanofibers for the Co-Delivery and Synergistic Release of Quercetin and Rosmarinic Acid via Electrospinning

by Nikoleta Stoyanova, Ani Georgieva, Reneta Toshkova and Mariya Spasova

Molecules 2026, 31(4), 704; https://doi.org/10.3390/molecules31040704 - 18 Feb 2026

Abstract

Natural polyphenols, particularly quercetin (QUE) and rosmarinic Acid (RA), possess significant synergistic therapeutic potential as potent antioxidants and anti-inflammatories. However, their poor stability, low water solubility, and resulting limited bioavailability severely hinder their effective clinical translation. This study addresses these fundamental limitations by [...] Read more.

Natural polyphenols, particularly quercetin (QUE) and rosmarinic Acid (RA), possess significant synergistic therapeutic potential as potent antioxidants and anti-inflammatories. However, their poor stability, low water solubility, and resulting limited bioavailability severely hinder their effective clinical translation. This study addresses these fundamental limitations by designing a novel advanced drug delivery platform utilizing electrospinning. We have fabricated composite high-molecular-weight poly(L-Lactic Acid) (PLA)/polyethylene glycol (PEG) nanofibers for the simultaneous co-delivery of both QUE and RA, optimizing compound stability and release kinetics. PLA provided mechanical integrity and sustained release properties, while the incorporation of PEG strategically enhanced the mat’s wettability, enabling precise control over initial drug dissolution. Comprehensive characterization confirmed uniform, bead-free morphology and high entrapment efficiency for both polyphenols. Crucially, the PLA/PEG blend successfully achieved a biphasic release profile, featuring an initial burst release mediated by PEG followed by a sustained release phase governed by the PLA matrix. Furthermore, the performed in vitro investigations using SH-4 melanoma cells and HaCaT normal keratinocytes revealed that the prepared novel materials containing the polyphenols possessed high anticancer activity to the used cancer cell line. However, the toxicity to the normal cell line is much lower. Therefore, this novel electrospun composite scaffold offers an effective strategy to enhance the stability, control the delivery, and maximize the synergistic therapeutic benefits of quercetin and rosmarinic Acid for applications in areas such as advanced wound care, tissue regeneration, and antitumor therapies. Full article

(This article belongs to the Special Issue Natural Products in Anticancer Activity: 2nd Edition)

► Show Figures

Figure 1

66 pages, 18380 KB

Open AccessPerspective

NMR and DFT Studies on Solvation Phenomena in Bioorganic Molecules, Natural Products and Model Compounds: Current and Future Perspectives for Atomic-Level Structures and Mechanistic Catalytic Reactions

by Michael G. Siskos and Ioannis P. Gerothanassis

Molecules 2026, 31(4), 703; https://doi.org/10.3390/molecules31040703 - 18 Feb 2026

Abstract

The structural role of solvation phenomena in bioorganic compounds has been documented sporadically over the last two decades, although they are of fundamental importance in a variety of chemical, physical, and biological processes. NMR chemical shifts depend on the electron densities around the [...] Read more.

The structural role of solvation phenomena in bioorganic compounds has been documented sporadically over the last two decades, although they are of fundamental importance in a variety of chemical, physical, and biological processes. NMR chemical shifts depend on the electron densities around the nuclei, which can be influenced by the surrounding environment. Solvent-dependent chemical shift variations, therefore, can provide important structural information on solute–solvent interactions, especially nuclei, which belong to polar groups, such as OH, NH, CONH, COOH, etc. Recent developments in quantum chemical methods for calculating NMR chemical shifts, especially those incorporating explicit solvent effects, and the exponential advances in computer power can provide an excellent methodology for the accurate calculation of chemical shifts in solution. Furthermore, comparison of density functional theory (DFT) calculated activation free energies with NMR experimentally determined values can provide a reliable method for investigating the role of solvents in various atomistic reaction mechanisms. It has been demonstrated that the combined use of NMR and DFT calculations represents the new frontier of our understanding of the role of solvents, at the atomic level, in molecular structures and in catalytic reactions of bioorganic molecules, natural products and model compounds. Full article

► Show Figures

Graphical abstract

19 pages, 1010 KB

Open AccessArticle

Phenolic Compounds Isolated from Salix cinerea L. with Emphasis on the Pharmaceutical Relevance of Flavan-3-ols

by Thomas Olaf Gruber, Katrin Kuck, Dejan Orčić, Jörg Heilmann, Gregor Aas and Guido Jürgenliemk

Molecules 2026, 31(4), 702; https://doi.org/10.3390/molecules31040702 - 18 Feb 2026

Abstract

During this phytochemical study, 13 compounds from the bark of Salix cinerea L. were isolated and their structures elucidated. These included two salicylic alcohol derivatives, one flavonol, two phenylpropanoids, two flavan-3-ols, two dimeric procyanidins, two dimeric prodelphinidins, and a unique ester of catechin [...] Read more.

During this phytochemical study, 13 compounds from the bark of Salix cinerea L. were isolated and their structures elucidated. These included two salicylic alcohol derivatives, one flavonol, two phenylpropanoids, two flavan-3-ols, two dimeric procyanidins, two dimeric prodelphinidins, and a unique ester of catechin (3-O-(1-hydroxy-6-oxo-2-cyclohexen-1-carboxylic acid), HCH-catechin). Furthermore, seasonal variations in the composition of Salix cortex regarding proanthocyanidins (PA) and the degree of polymerization were examined using NMR spectroscopy, revealing an increase in polymerization throughout the growing season 2020 associated with a consistent hydroxylation pattern in the B-ring. The isolated HCH-catechin was tested in vitro for its inhibitory effect on TNF-α-induced ICAM-1 expression in human microvascular endothelial cells (HMEC-1). A 24 h treatment with a 25 µM solution of HCH-catechin significantly reduced ICAM-1 expression (83.7 ± 3.2%) compared to unsubstituted catechin (97.9 ± 4.4%). Additionally, during a mass-spectrometric screening, numerous HCH adducts within the PA fraction could be identified, allowing for the proposition of a characteristic fragmentation pattern. This study establishes a foundation for a comprehensive assessment of the phenolic, PA-rich fraction in willow bark, particularly the occurrence of HCH adducts, which may contribute to the medicinal properties of Salicis cortex. Findings on seasonal variations and mass spectrometric profiling offer new insights into the quality standards for Salicis cortex as a medicinal remedy. Full article

(This article belongs to the Section Molecular Structure)

18 pages, 2269 KB

Open AccessArticle

A Potent Quinone Reductase Encoded by ywqN (Qnr1) Protects Bacillus subtilis from Oxygen Radical Genotoxicity

by Beatriz R. González, Norma Ramírez, Karen Abundiz-Yáñez, Víctor M. Ayala-García, Luz I. Valenzuela-García, Eduardo A. Robleto and Mario Pedraza-Reyes

Molecules 2026, 31(4), 701; https://doi.org/10.3390/molecules31040701 - 17 Feb 2026

Abstract

ywqN encodes a protein with an unassigned function that shares partial 3D homology with B. subtilis YhdA, Pseudomonas putida ChrR, and Escherichia coli YieF, which are NADP(H)/FMN-dependent oxidoreductases that catalyze the reduction of diverse chemical pollutants, including Cr(VI). Here, we report that a [...] Read more.

ywqN encodes a protein with an unassigned function that shares partial 3D homology with B. subtilis YhdA, Pseudomonas putida ChrR, and Escherichia coli YieF, which are NADP(H)/FMN-dependent oxidoreductases that catalyze the reduction of diverse chemical pollutants, including Cr(VI). Here, we report that a recombinant His₆-YwqN protein displays marginal chromate reductase activity but is capable of reducing synthetic azo dyes. Remarkably, His₆-YwqN exhibits a potent quinone reductase activity, catalyzing the reduction of menadione (MD) and 1,4-naphthoquinone (NQ). The individual and combined roles of YwqN and YhdA in protecting B. subtilis from ROS-promoting agents were further tested. Sensitization to the oxidizing agent H₂O₂ required the simultaneous loss of both YwqN and YhdA. In contrast, strains deficient in ywqN, either alone or in combination with yhdA, exhibited similar but higher susceptibilities to the superoxide-generating agent MD compared with the WT strain. These results indicate that YwqN and YhdA contribute to protection against the deleterious effects of ROS in B. subtilis. Further results revealed that while YwqN, but not YhdA, prevented MD-induced mutagenesis, both proteins synergistically prevented Rif^R mutations induced by H₂O₂. Furthermore, overexpression of YwqN suppressed the hypermutagenesis phenotype of a B. subtilis strain deficient in the prevention/repair oxidized guanine (GO) system, which is prone to accumulate 8-oxoGs. In summary, YwqN counteracts the cytotoxic and genotoxic effects promoted by ROS in B. subtilis and represents a potential tool for the remediation of soils and effluents contaminated with carcinogenic azo dyes. Full article

► Show Figures

Graphical abstract

18 pages, 2786 KB

Open AccessArticle

Development and Validation of a Confirmatory LC-MS/MS Method Using QuEChERS for Determination of Nitrofuran Metabolites in Eggs According to EU Regulation 2021/808

by Elmira Marku, Kozeta Vaso, Martin Danaher, Erinda Pllaha, Suela Teqja, Jonida Canaj, Ina Pasho and Ilir Ajdini

Molecules 2026, 31(4), 700; https://doi.org/10.3390/molecules31040700 - 17 Feb 2026

Abstract

Nitrofurans are banned veterinary medicinal products due to their carcinogenic and mutagenic properties; however, their protein-bound metabolites (AOZ, AMOZ, AHD, SEM, and DNSAH) may persist in food-producing animals, particularly in eggs. Reliable confirmatory methods are therefore essential for residue monitoring under the stringent [...] Read more.

Nitrofurans are banned veterinary medicinal products due to their carcinogenic and mutagenic properties; however, their protein-bound metabolites (AOZ, AMOZ, AHD, SEM, and DNSAH) may persist in food-producing animals, particularly in eggs. Reliable confirmatory methods are therefore essential for residue monitoring under the stringent requirements of Commission Implementing Regulation (EU) 2021/808. This study reports the development and validation of a sensitive and selective LC–MS/MS method combining acid hydrolysis, 2-nitrobenzaldehyde derivatization, and QuEChERS extraction for the determination of nitrofuran metabolites in eggs. Chromatographic separation was carried out using a phenyl-hexyl column, and detection using a tandem mass spectrometer, supported by isotope-labeled internal standards, ensured robust identification and quantification. Linearity was satisfactory over the investigated concentration range (R² > 0.99), with recoveries between 82 and 109%. The method’s precision was acceptable, with repeatability RSD values below 10% and within-laboratory reproducibility RSD values below 22%. Matrix effects were effectively controlled, remaining within ±20% following internal standard normalization. Decision limits (CCα) ranged from 0.29 to 0.37 µg/kg, well below the EU reference point for action of 0.5 µg/kg. The method’s performance was further confirmed through participation in an accredited proficiency test scheme. Overall, the validated method provides a reliable analytical tool for routine official control laboratories, enabling the sensitive confirmatory detection of banned nitrofuran residues in eggs and supporting food safety and regulatory compliance. Full article

(This article belongs to the Section Food Chemistry)

► Show Figures

Figure 1

36 pages, 5378 KB

Open AccessArticle

Discovery of Potent PDE4 Inhibitors with 3(2H)-Pyridazinone Scaffold: Synthesis, In Silico Studies and In Vitro/Vivo Evaluation

by Claudia Vergelli, Letizia Crocetti, Gabriella Guerrini, Fabrizio Melani, Jordi Gracia, Maria Antonia Buil, Yolanda Garrido, Lluis Pagès, Joan Taltavull, Amadeu Gavaldà, Elena Calama and Maria Paola Giovannoni

Molecules 2026, 31(4), 699; https://doi.org/10.3390/molecules31040699 - 17 Feb 2026

Abstract

Phospodiesterase 4 (PDE4) has long been an attractive target not only for the anti-inflammatory therapy in respiratory diseases, but also for other pathologies such as psoriatic arthritis and atopic dermatitis. In this study, we report the synthesis of 5-acetyl-2-ethyl-6-phenyl-3(2H)-pyridazinones differently substituted at position [...] Read more.

Phospodiesterase 4 (PDE4) has long been an attractive target not only for the anti-inflammatory therapy in respiratory diseases, but also for other pathologies such as psoriatic arthritis and atopic dermatitis. In this study, we report the synthesis of 5-acetyl-2-ethyl-6-phenyl-3(2H)-pyridazinones differently substituted at position 4 with a variety of aryl/alkylamines, which act as potent PDE4B1 inhibitors in the low nanomolar range. The selectivity toward PDE4A4, PDE4D3 and HARBS, as well as the ability to inhibit TNFα production in human whole blood (hWB), was also evaluated for the most potent products, resulting in a small cluster of compounds with an interesting profile and two selected products (3a and 3k) have been in depth investigated with additional in vitro tests on metabolism and in vivo studies. Finally, molecular docking and minimization of the ligand-enzyme complexes were carried out. Full article

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

► Show Figures

Figure 1

12 pages, 1815 KB

Open AccessArticle

Unlocking the Potential of Cranberry (Vaccinium macrocarpon Aiton) Pruning Biomass: Phenolic Composition and Antioxidant Properties of Response Surface Methodology Optimized Extracts

by Tomasz Piechowiak, Ireneusz Kapusta, Maciej Balawejder, Radosław Józefczyk and Natalia Matłok

Molecules 2026, 31(4), 698; https://doi.org/10.3390/molecules31040698 - 17 Feb 2026

Abstract

The aim of this study was to investigate the chemical composition and biological activity of extracts obtained from vegetative cranberry biomass generated during plantation rejuvenation. This biomass, composed mainly of young shoots removed during routine agricultural maintenance, represents a readily available and currently [...] Read more.

The aim of this study was to investigate the chemical composition and biological activity of extracts obtained from vegetative cranberry biomass generated during plantation rejuvenation. This biomass, composed mainly of young shoots removed during routine agricultural maintenance, represents a readily available and currently underutilized by-product of commercial cranberry (Vaccinium macrocarpon Aiton) cultivation. Extraction optimization was performed using response surface methodology (RSM), which enabled both the assessment of the effects of process variables and the identification of conditions ensuring maximal extraction efficiency. The optimal parameters were determined to be 40% ethanol, a temperature of 60 °C, and an extraction time of 49.44 min, and these conditions were further validated through an additional triplicate extraction. The resulting extract exhibited a high antioxidant activity (429–490 mg Trolox equivalents per gram) and was rich in phenolic compounds, particularly quercetin glycoside derivatives. The chemical profile and bioactivity of the extract highlight the considerable potential of cranberry pruning biomass as an alternative, sustainable source of high-value phytochemicals. Its valorization may support the development of environmentally friendly extraction technologies and contribute to closing the resource loop within agricultural production systems. Full article

► Show Figures

Figure 1

22 pages, 5609 KB

Open AccessArticle

Cissus verticillata Leaf Extract Decreases the Production of AGEs and ROS In Vitro

by Felipe Nunes Cardoso, Emanuel Victor dos Santos Nunes, Ingrid Delbone Figueiredo, Winner Duque Rodrigues, Renata Pires Assis, André Gonzaga dos Santos, Luis Vitor Silva do Sacramento, Iguatemy Lourenço Brunetti, Alan Cesar Pilon and Amanda Martins Baviera

Molecules 2026, 31(4), 697; https://doi.org/10.3390/molecules31040697 - 17 Feb 2026

Abstract

Cissus verticillata (plant-insulin) is used in the Brazilian popular medicine to treat symptoms of diabetes. Studies about its ability to contrast glycoxidative stress is lacking, which may add mechanistic information about its effects on treat diabetic complications. This study investigated the ability of [...] Read more.

Cissus verticillata (plant-insulin) is used in the Brazilian popular medicine to treat symptoms of diabetes. Studies about its ability to contrast glycoxidative stress is lacking, which may add mechanistic information about its effects on treat diabetic complications. This study investigated the ability of Cissus verticillata leaf hydroethanolic extract (CvExt) to scavenge reactive oxygen species (ROS) and to inhibit the formation of advanced glycation end products (AGEs). ROS scavenging assays were used to test CvExt antioxidant activity. Incubations of bovine serum albumin with glucose (0.5 M) or methylglyoxal (2 mM) and CvExt (250, 125, and 62.5 μg/mL) were used to test the antiglycation activity, by monitoring fluorescent AGEs, markers of amino acid oxidation, and protein carbonyl groups (PCO). The plant extract was submitted to liquid−liquid extractions, fractions were analyzed by liquid chromatography with tandem mass spectrometry, and the data obtained were subjected to partial least-squares discriminant analysis. CvExt scavenged ROS inhibited the formation of AGEs and amino acid oxidation products, and decreased PCO levels. The main metabolites found in CvExt were flavonoids, cinnamic acid derivatives, coumarins, free amino acids, and some lipophilic compounds. CvExt inhibited glycoxidative stress in vitro, which can be associated with its complex chemical composition. Full article

► Show Figures

Figure 1

23 pages, 3128 KB

Open AccessArticle

Dual Inhibition of PB2 and JAK2 for Influenza: A Strategy Combining Antiviral and Host-Directed Immune Modulation

by Binhao Rong, Yujian Yang, Kunyu Lu, Xingyu Zhou, Peisen Zheng, Xinxin Lin, Yuanmei Wen, Shudong Lin, Xinshan Deng, Qifan Zhou and Shuwen Liu

Molecules 2026, 31(4), 696; https://doi.org/10.3390/molecules31040696 - 17 Feb 2026

Abstract

Influenza virus infection remains a major global health burden, with severe disease outcomes driven not only by viral replication but also by excessive host inflammatory responses. Current antiviral therapies predominantly target viral components and fail to adequately control virus-induced hyperinflammation. In this study, [...] Read more.

Influenza virus infection remains a major global health burden, with severe disease outcomes driven not only by viral replication but also by excessive host inflammatory responses. Current antiviral therapies predominantly target viral components and fail to adequately control virus-induced hyperinflammation. In this study, we report a dual-target therapeutic strategy integrating direct antiviral activity with host-directed immunomodulation. Using a molecular hybridization approach, we designed and synthesized several dual-target inhibitors simultaneously targeting the influenza virus PB2 cap-binding subunit and host JAK2 kinase. Among them, PB05 emerged as the most promising candidate and was systematically evaluated in vitro and in vivo. PB05 exhibited potent broad-spectrum antiviral activity against influenza A viruses, with nanomolar EC₅₀ values. Mechanistic studies demonstrated that PB05 directly binds to the PB2 cap-binding domain, thereby disrupting viral cap-snatching and RNA synthesis. In parallel, PB05 inhibited JAK–STAT signaling by suppressing STAT2 phosphorylation and downstream ISRE-mediated transcription, leading to a marked reduction in pro-inflammatory cytokine production, including IL-6, IL-1β, and IFN-β, in infected or stimulated immune cells. In a lethal influenza A/PR/8/34 (H1N1) mouse model, oral administration of PB05 at 100 mg/kg (twice daily) markedly decreased lung viral titers, attenuated pulmonary tissue damage and edema, and moderated excessive inflammatory responses. Collectively, these findings identify PB05 as a dual PB2/JAK2 inhibitor that effectively couples antiviral efficacy with immunomodulatory activity, promoting a therapeutic strategy for the treatment of severe influenza and other viral diseases associated with excessive inflammation. Full article

(This article belongs to the Section Medicinal Chemistry)

19 pages, 4791 KB

Open AccessArticle

Postbiotic Metabolites of Proanthocyanidins Reduce Adipogenesis In Vitro by Suppressing De Novo Lipogenesis

by Wasitha P. D. W. Thilakarathna, Madumani Amararathna and H. P. Vasantha Rupasinghe

Molecules 2026, 31(4), 695; https://doi.org/10.3390/molecules31040695 - 17 Feb 2026

Abstract

Proanthocyanidins (PACs) are a key group of bioactive phytochemicals known to provide health benefits. Most PACs are non-bioavailable polymeric molecules that need to be biotransformed by colonic microbes into simple metabolites to exert their pharmacological effects. In this study, six previously unexamined PAC [...] Read more.

Proanthocyanidins (PACs) are a key group of bioactive phytochemicals known to provide health benefits. Most PACs are non-bioavailable polymeric molecules that need to be biotransformed by colonic microbes into simple metabolites to exert their pharmacological effects. In this study, six previously unexamined PAC metabolites from Saccharomyces cerevisiae, 3-aminophenol (3-AMP), 3-aminosalicylic acid, 2,4-dihydroxy-6-methylbenzaldehyde, 4-hydroxyphenylacetamide (4-HPA), 3-phenyllactic acid, and 2,4,6-trihydroxyacetophenone, were tested for their antiadipogenic activity using an insulin-dependent 3T3-L1 preadipocyte differentiation model. Lipid accumulation in differentiating preadipocytes was visualized and measured with the Oil Red O assay. Only 3-AMP and 4-HPA significantly reduced lipid accumulation at a concentration of 25 µM. To understand the cellular mechanisms, protein levels of key regulators of adipogenesis and lipid metabolism were analyzed using Western blotting. 3-AMP and 4-HPA may attenuate lipid accumulation by suppressing de novo lipogenesis, with 3-AMP downregulating the peroxisome proliferator-activated receptor (PPAR)-γ/acetyl-CoA carboxylase (ACC)/fatty acid synthase (FAS) axis and 4-HPA primarily inhibiting ACC/FAS signaling. Molecular docking studies indicated that 3-AMP may downregulate PPAR-γ expression through competitive inhibition of insulin receptors. These preliminary findings suggest that 3-AMP and 4-HPA exhibit potential antiadipogenic effects, highlighting PAC-derived postbiotics as promising nutraceuticals for mitigating obesity risk. Full article

(This article belongs to the Special Issue Discovering the Pharmacological and Medicinal Potentials of Plant Flavonoids and Other Polyphenols from Nature)

► Show Figures

Figure 1

19 pages, 3422 KB

Open AccessArticle

Thermodynamic and Kinetic Analysis of Galactose Oxidase Direct Electron Transfer on Carboxyl-Terminated SAM-Modified Gold Electrodes

by Martha Leticia Jiménez-González, Gilberto Rocha-Ortiz, Luis Gabriel Talavera-Contreras, Jose de Jésus Gómez-Guzmán, René Antaño-Lopez, Marisela Cruz-Ramírez and Luis Ortiz-Frade

Molecules 2026, 31(4), 694; https://doi.org/10.3390/molecules31040694 - 17 Feb 2026

Abstract

This study addresses the thermodynamic aspects of galactose oxidase (GAOx) adsorption and redox behavior on gold electrodes modified with self-assembled monolayers (SAMs) derived from thiocarboxylic acids, namely N-acetyl-L-cysteine (NAC), mercaptosuccinic acid (MSA), mercaptoacetic acid (MAA), and L-cysteine (Cys). The electrochemical response of GAOx [...] Read more.

This study addresses the thermodynamic aspects of galactose oxidase (GAOx) adsorption and redox behavior on gold electrodes modified with self-assembled monolayers (SAMs) derived from thiocarboxylic acids, namely N-acetyl-L-cysteine (NAC), mercaptosuccinic acid (MSA), mercaptoacetic acid (MAA), and L-cysteine (Cys). The electrochemical response of GAOx immobilized on these SAM-modified surfaces was analyzed to extract key thermodynamic parameters governing enzyme–electrode interactions, including the formal redox potential (E°), surface excess (Γ), potential of zero charge (E_zc), adsorption free energy (∆G_add), differential capacitance (C_dl), and surface tension (γ). The results demonstrate that the nature of the terminal functional group of the SAM significantly influences the thermodynamic stabilization of GAOx at the gold interface. Shifts in the redox potential are attributed to specific coordination and electrostatic interactions between the SAM functional groups and the GAOx metal center, leading to distinct interfacial energy landscapes. Overall, the SAM-modified electrodes provide a well-defined thermodynamic framework to probe enzyme orientation, interfacial charge distribution, and stabilization of the redox-active state of GAOx during direct electron transfer. These results offer guidelines based on thermodynamic and kinetic principles for customizing enzyme–electrode interfaces, which can enhance the efficiency, stability, and consistency of third-generation electrochemical biosensors. Full article

(This article belongs to the Special Issue Advances in Electrochemical Reactions, Mechanisms and Sensing Applications)

► Show Figures

Figure 1

33 pages, 1190 KB

Open AccessReview

Harnessing Endophytic Fungi as a Sustainable Source of Novel Anticancer Agents: Opportunities, Challenges, and Future Directions

by Elly Lowen, Simon E. Moulton, Enzo A. Palombo, Faith Kwa and Bita Zaferanloo

Molecules 2026, 31(4), 693; https://doi.org/10.3390/molecules31040693 - 17 Feb 2026

Abstract

Despite significant advances in oncology, current cancer therapies remain constrained by toxicity, resistance, and limited selectivity. Endophytic fungi symbiotic microorganisms inhabiting plant tissues represent a sustainable and underexplored source of structurally diverse anticancer metabolites. These include alkaloids, terpenoids, polyketides, and peptides that disrupt [...] Read more.

Despite significant advances in oncology, current cancer therapies remain constrained by toxicity, resistance, and limited selectivity. Endophytic fungi symbiotic microorganisms inhabiting plant tissues represent a sustainable and underexplored source of structurally diverse anticancer metabolites. These include alkaloids, terpenoids, polyketides, and peptides that disrupt microtubule dynamics, interfere with DNA replication, and induce mitochondrial-mediated apoptosis. They also modulate key oncogenic signalling pathways such as nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), thereby enhancing the efficacy of existing chemotherapies. Endophyte derived compounds further inhibit angiogenesis, suppress metastasis, and stimulate immune responses, offering multi-target mechanisms with reduced toxicity. This review examines strategies that enhance the discovery and yield of these bioactive metabolites, including One Strain Many Compounds (OSMAC), microbial co-culture, epigenetic activation, genome mining, and synthetic biology. A comparative assessment of endophyte-derived versus conventional anticancer agents highlights their potential for scalable, eco-sustainable production. Collectively, endophytic fungi are positioned as promising contributors to the next generation of accessible, cost-effective, and environmentally responsible anticancer therapies. Full article

(This article belongs to the Special Issue Microbial Natural Products: A Promising Source for Medical Application (2nd Edition))

► Show Figures

Figure 1

20 pages, 1237 KB

Open AccessArticle

2-MCPD-Induced Effects in the Heart: Toxicological and Mechanistic Implications from Comparative Proteomic Analyses in Rats

by Axel Oberemm, Andreas Eisenreich, Katharina Sommerkorn, Anna Reinhold, Christine Meckert and Mario E. Götz

Molecules 2026, 31(4), 692; https://doi.org/10.3390/molecules31040692 - 17 Feb 2026

Abstract

The toxic actions of 2-monochloropropane-1,3-diol (2-MCPD) are still less well understood than those of 3-monochloropropane-1,2-diol (3-MCPD). The toxic effects of 2-MCPD on the heart, especially at the proteomic level, were recently investigated by researchers in a subacute (28 days, in 2017) and in [...] Read more.

The toxic actions of 2-monochloropropane-1,3-diol (2-MCPD) are still less well understood than those of 3-monochloropropane-1,2-diol (3-MCPD). The toxic effects of 2-MCPD on the heart, especially at the proteomic level, were recently investigated by researchers in a subacute (28 days, in 2017) and in a subchronic (90 days, in 2024) oral toxicity rat study. Here, we set out to perform an updated analysis and re-evaluation of these proteomic in vivo data in a comparative manner and in the context of 2-MCPD metabolism, focusing in particular on mitochondrial energy metabolism and the maintenance of the structural integrity and function of the heart. The aim of our project was to develop further reasonable, toxicologically relevant research hypotheses for future studies addressing this topic in order to shed more light on the—so far—rather limited knowledge of the toxicological properties and modes of action of 2-MCPD. Our updated data analysis and comparative re-evaluation revealed strong indications of cytoskeletal protein deregulation, indicative of cardiomyocyte degeneration, and the deregulation of enzyme proteoforms linked to carbohydrate utilization and mitochondrial functions. This led us to hypothesize that reactive metabolites of 2-MCPD, other than those formed from 3-MCPD, could impair mitochondrial pyruvate utilization and mitochondrial energy production, potentially resulting in cardiac functional heart failure in rats at doses slightly higher than 10 mg 2-MCPD per kg bw/day. Thus, we postulate the intermediate formation of some putative aldehydic and acidic metabolites following oral 2-MCPD exposure that might be causative of cardiotoxicity in rats. Full article

(This article belongs to the Section Food Chemistry)

► Show Figures

Graphical abstract

Journal Description

Molecules

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI