Molecules

11 pages, 4960 KB

Open AccessArticle

Halogen as Template to Modulate the Structures of the Nanocage-Based Silver(I)-Thiolate Coordination Polymers

by Chunhong Tan, Li Tang, Jiajia Tan, Jinrong Zhang, Juan Zhou, Linmao Yin and Xiao-Feng Wang

Molecules 2026, 31(2), 331; https://doi.org/10.3390/molecules31020331 (registering DOI) - 19 Jan 2026

Abstract

By the reaction of AgNO₃, 2-methyl-2-propanethiol (HStBu), with various-sized halogen ions as templates, three multi-nuclear silver-thiolate cluster-based chain-like coordination polymers, [Ag₆(μ-SBu)₆]_n (USC-CP-2), [Ag₆(μ-StBu)₅ [...] Read more.

By the reaction of AgNO₃, 2-methyl-2-propanethiol (HStBu), with various-sized halogen ions as templates, three multi-nuclear silver-thiolate cluster-based chain-like coordination polymers, [Ag₆(μ-SBu)₆]_n (USC-CP-2), [Ag₆(μ-StBu)₅Br]_n (USC-CP-4) and [Ag₁₄(μ-StBu)₁₂I₂]_n (USC-CP-3) constructed by different Ag(I)-nanocages, have been synthesized and characterized by X-ray diffraction analyses. With F⁻, Cl⁻ or without template, USC-CP-2 exhibits a one-dimensional structure composed of detached Ag₆-cages, absent of fluoride or chloridion. While with Br⁻ and I⁻, USC-CP-4 and USC-CP-3, two distinct halogen-templating multi-sliver cages-based chain-like polymeric structures have been observed, which are a mono-Br⁻ encapsulated Ag₈-cage, or a dual-I⁻ embedded Ag₁₆-cage, respectively. In these three compounds, the multi-Ag(I) cages were self-assembled by Ag-S bonds through bridged μ₂-StBu ligands, and stabilized argentophilic interactions between neighboring silver atoms. This study demonstrates that the halide anions of varying sizes play a critical role in inducing the nucleation and structural evolution of the silver-thiolate clusters. Full article

(This article belongs to the Section Inorganic Chemistry)

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22 pages, 2659 KB

Open AccessReview

Research and Application of the Polyene Macrolide Antibiotic Nystatin

by Xiaofeng Liu, Jiamin Zhuo, Zherui Chen, Yao Zhang, Wei Jiang and Rongfa Guan

Molecules 2026, 31(2), 330; https://doi.org/10.3390/molecules31020330 (registering DOI) - 19 Jan 2026

Abstract

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such [...] Read more.

Nystatin is a polyene macrolide antibiotic with broad-spectrum antifungal activity and serves as a key therapeutic agent for superficial fungal infections. This review systematically elaborates on its multicomponent chemical nature, its mechanism of action targeting ergosterol, and highlights the potential adverse effects, such as cardiotoxicity, associated with impurities like RT6 (albonoursin). The fundamental analytical techniques for quality control are outlined. Furthermore, the clinical applications and combination therapy strategies of nystatin in treating oral diseases, vaginitis, and otitis externa are summarized in detail. Regarding biosynthesis, the assembly mechanism of nystatin A₁ via the type I polyketide synthase pathway and its subsequent modification processes are thoroughly discussed. Emphasis is placed on the latest advances and potential of gene-editing technologies, particularly CRISPR/Cas9, in the targeted knockout of genes responsible for toxic components and in optimizing production strains to enhance nystatin yield and purity. Finally, this review prospects the future development of nystatin towards improved safety and efficacy through structural optimization, innovative delivery systems, and synthetic biology strategies, aiming to provide a reference for its further research and clinical application. Full article

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15 pages, 888 KB

Open AccessArticle

Utilization of Quinoa Post-Fermentation Waste as a Medium for Carotenoid Production by Yeast

by Ewa Kulczyk-Małysa, Elżbieta Bogusławska-Wąs, Patrycja Jaroszek, Katarzyna Szkolnicka and Artur Rybarczyk

Molecules 2026, 31(2), 329; https://doi.org/10.3390/molecules31020329 (registering DOI) - 18 Jan 2026

Abstract

Carotenoids are a diverse group of isoprenoid compounds found in nature. As natural pigments and bioactive compounds, carotenoids are used in various industries as functional additives. The increasing knowledge about the disadvantages of synthetic carotenoid production has drawn attention to the potential of [...] Read more.

Carotenoids are a diverse group of isoprenoid compounds found in nature. As natural pigments and bioactive compounds, carotenoids are used in various industries as functional additives. The increasing knowledge about the disadvantages of synthetic carotenoid production has drawn attention to the potential of carotenogenic yeasts and the use of food industry waste. This study analyzed the potential of post-fermentation waste from fermented quinoa production as a culture medium. For this purpose, reference yeast strains and strains isolated from various environments were used. The C:N ratio in the waste used was determined, and then the yeast was cultured in waste medium with the isolated strains and in a mixed culture with L. plantarum, using three culture variants. In subsequent stages, carotenoid powder was produced, and the carotenoid content, antioxidant capacity, and FTIR spectrum distribution were determined. The studies confirmed the possibility of using plant ferments as culture media. The extraction of powder enabled the concentration of carotenoids, obtaining the highest total fraction of carotenoids (TFC) for strains R-1 (2.85 mg/g d.w.) and R-2 (3.05 mg/g d.w.). FTIR spectra confirmed the presence of functional groups found in β-carotene standards in the resulting powders. At the same time, the obtained formulate exhibited bioactive properties by binding DPPH oxygen free radicals at a level of 66.80–78.05%. Full article

(This article belongs to the Special Issue New Development in Fermented Products—Third Edition)

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17 pages, 2376 KB

Open AccessArticle

Chitosan Nanoparticles as a Biostimulant During In Vitro Multiplication of Vanilla Using Temporary Immersion Bioreactors

by Víctor Adrián Delgado-Rivera, María Karen Serrano-Fuentes, José María Rivera-Villanueva, Juan Antonio Pérez-Sato and Jericó Jabín Bello-Bello

Molecules 2026, 31(2), 328; https://doi.org/10.3390/molecules31020328 (registering DOI) - 18 Jan 2026

Abstract

This research aimed to assess the effect of chitosan nanoparticles (ChNPs) during in vitro shoot proliferation of vanilla using temporary immersion bioreactors (TIB). TIB culture is a biotechnological process that uses semiautomated containers for the production of explants exposed in liquid culture medium. [...] Read more.

This research aimed to assess the effect of chitosan nanoparticles (ChNPs) during in vitro shoot proliferation of vanilla using temporary immersion bioreactors (TIB). TIB culture is a biotechnological process that uses semiautomated containers for the production of explants exposed in liquid culture medium. Concentrations of control, 25, 50, 100, 200, and 400 mg/L ChNPs were evaluated in Murashige and Skoog culture medium. Morphological characterization of ChNPs was performed using scanning electron microscopy. At 60 days of culture, survival (%), development variables, photosynthetic pigment content, lipid peroxidation expressed in malondialdehyde, total phenolic content (TPC), hydrogen peroxide (H₂O₂) content, and total antioxidant capacity (TAC) expressed in trolox equivalents were evaluated. The data were analyzed with analysis of variance, with a Tukey test (p ≤ 0.05) using SPSS statistics software, version 29. The results revealed that the greatest survival (%) was obtained at concentrations of control, 25, and 50 mg/L ChNPs, while the lowest survival (%) was observed at concentrations of 400 mg/L ChNPs. Growth stimulation was found, as well as an increase in chlorophyll and β-carotene at concentrations of 25 and 50 mg/L ChNPs. The level of H₂O₂ increased at 25 and 50 mg/L ChNPs. Lipid peroxidation showed no differences among treatments. TPC increased at 100 and 200 mg/L ChNPs, while TAC increased at 200 and 400 mg/L ChNPs. In conclusion, the administration of ChNPs at low concentrations can stimulate growth, while at high concentrations they can inhibit it, a response known as hormesis or hormetic effect. Full article

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

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17 pages, 1455 KB

Open AccessArticle

Genipin as an Effective Crosslinker for High-Performance and Flexible Direct-Printed Bioelectrodes

by Kornelia Bobrowska, Marcin Urbanowicz, Agnieszka Paziewska-Nowak, Marek Dawgul and Kamila Sadowska

Molecules 2026, 31(2), 327; https://doi.org/10.3390/molecules31020327 (registering DOI) - 17 Jan 2026

Abstract

The development of efficient bioelectrodes requires suitable fabrication strategies, starting with the electrode material, which affects the electron transfer between the biocatalyst and the electrode surface. Then, selection and adjustment of the enzyme immobilization conditions are essential to enhance the performance of the [...] Read more.

The development of efficient bioelectrodes requires suitable fabrication strategies, starting with the electrode material, which affects the electron transfer between the biocatalyst and the electrode surface. Then, selection and adjustment of the enzyme immobilization conditions are essential to enhance the performance of the bioelectrodes for their desirable utility. In this study, we report the fabrication of a high-performance bioelectrode using a one-step crosslinking of FAD-dependent glucose dehydrogenase (FAD-GDH) and thionine acetate as a redox mediator, with genipin serving as a natural, biocompatible crosslinker. Electrodes were manufactured on flexible polyester substrates using a direct printing technique, enabling reproducible and low-cost production. Among the tested crosslinkers, genipin significantly enhanced the catalytic performance of bioelectrodes. Comparative studies on graphite, silver, and gold electrode materials identified graphite as the most suitable due to its extended electroactive surface area. The developed bioelectrodes applied to glucose biosensing demonstrated a linear amperometric response to glucose in the range of 0.02–2 mM and 0.048–30 mM, covering clinically relevant concentrations. The application of artificial sweat confirmed high detection accuracy. These findings highlight the potential integration of genipin-based enzyme–mediator networks for future non-invasive sweat glucose monitoring platforms. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules—Recent Advances in Electrochemistry)

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26 pages, 2472 KB

Open AccessArticle

Chemical Profiling and Cheminformatic Insights into Piper Essential Oils as Sustainable Antimicrobial Agents Against Pathogens of Cocoa Crops

by Diannefair Duarte, Marcial Fuentes-Estrada, Yorladys Martínez Aroca, Paloma Sendoya-Gutiérrez, Manuel I. Osorio, Osvaldo Yáñez, Carlos Areche, Elena Stashenko and Olimpo García-Beltrán

Molecules 2026, 31(2), 326; https://doi.org/10.3390/molecules31020326 (registering DOI) - 17 Jan 2026

Abstract

This study evaluates the chemical profile and antifungal efficacy of essential oils from Piper glabratum, Piper friedrichsthalii, and Piper cumanense against the cocoa pathogens Moniliophthora roreri and Phytophthora palmivora. Microwave-assisted hydrodistillation followed by GC-MS analysis identified 80 constituents, predominantly monoterpenes [...] Read more.

This study evaluates the chemical profile and antifungal efficacy of essential oils from Piper glabratum, Piper friedrichsthalii, and Piper cumanense against the cocoa pathogens Moniliophthora roreri and Phytophthora palmivora. Microwave-assisted hydrodistillation followed by GC-MS analysis identified 80 constituents, predominantly monoterpenes and sesquiterpenes, which exhibited significant mycelial inhibition comparable to commercial fungicides. Beyond basic characterization, a comprehensive chemoinformatic analysis was conducted to elucidate the molecular mechanisms driving this bioactivity. The computed physicochemical landscape reveals a dominant lipophilic profile (average LogP 3.4) and low polarity (TPSA 11.5 Å²), characteristics essential for effective fungal membrane penetration. Structural mining identified conserved benzene and cyclohexene scaffolds alongside specific 1,3-benzodioxole moieties, while Maximum Common Substructure (MCS) analysis uncovered high similarity clusters among phenylpropanoids and sesquiterpenes. These findings suggest a synergistic mode of action where conserved structural backbones and interchangeable diastereomers facilitate membrane destabilization and ion leakage. Consequently, the integrative chemoinformatic profiling elucidates the molecular basis of this efficacy, positioning these Piper essential oils not merely as empirical alternatives, but as sources of rationally defined synergistic scaffolds for next-generation sustainable fungicides. Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Sources: Discovery, Evaluation and Applications, 2nd Edition)

25 pages, 3112 KB

Open AccessReview

The Emerging Promise of Pentacyclic Triterpenoid Derivatives as Novel Antiviral Agents Against SARS-CoV-2 Variants

by Xin Wan, Xiaoxuan Cui, Ke Liang, Junran Huang, Kangan Chen, Wen Chen and Gaopeng Song

Molecules 2026, 31(2), 325; https://doi.org/10.3390/molecules31020325 (registering DOI) - 17 Jan 2026

Abstract

The continuous emergence of SARS-CoV-2 variants, especially the Omicron strain with its heightened transmissibility, has posed ongoing challenges to the efficacy of existing vaccine and drug regimens. This situation highlights the pressing demand for antiviral drugs employing novel mechanisms of action. Pentacyclic triterpenoids [...] Read more.

The continuous emergence of SARS-CoV-2 variants, especially the Omicron strain with its heightened transmissibility, has posed ongoing challenges to the efficacy of existing vaccine and drug regimens. This situation highlights the pressing demand for antiviral drugs employing novel mechanisms of action. Pentacyclic triterpenoids (PTs), a structurally varied group of compounds derived from plants, exhibit both antiviral and anti-inflammatory activities, making them attractive candidates for further therapeutic development. These natural products, along with their saponin derivatives, show broad-spectrum inhibitory effects against multiple SARS-CoV-2 variants (from Alpha to Omicron) via interactions with multiple targets, such as the spike protein, main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and inflammatory signaling pathways. This review consolidates recent findings on PTs and their saponins, emphasizing their influence on the key structural features required for inhibiting viral attachment, membrane fusion, reverse transcription, and protease function. We systematically summarized the structure–activity relationships and their antiviral results of PTs based on different target proteins in existing studies. Furthermore, this work points toward new strategies for designing multi-target PT-based inhibitors with improved efficacy against Omicron and future variants. Full article

(This article belongs to the Special Issue New Strategies for Drug Development)

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41 pages, 2263 KB

Open AccessReview

Bacteriophage Therapy: Overcoming Antimicrobial Resistance Through Advanced Delivery Methods

by Marcin Wacnik, Emilia Hauza, Aneta Skaradzińska and Paulina Śliwka

Molecules 2026, 31(2), 324; https://doi.org/10.3390/molecules31020324 (registering DOI) - 17 Jan 2026

Abstract

Microbial resistance to antibiotics necessitates the development of alternative treatments to address the challenges posed by severe bacterial infections. Bacteriophages are regaining clinical relevance, but the effectiveness of phage therapy depends directly on the route of administration and the carrier used. This review [...] Read more.

Microbial resistance to antibiotics necessitates the development of alternative treatments to address the challenges posed by severe bacterial infections. Bacteriophages are regaining clinical relevance, but the effectiveness of phage therapy depends directly on the route of administration and the carrier used. This review provides a critical overview of the therapeutic potential of phages, emphasizing different strategies for delivery to the site of infection. We focus on the preclinical and clinical data on phage therapies using various routes of administration, such as oral, intravenous, inhalation, topical, and local administration to joints and bones. In view of different phage formulations, including liquid suspension, phages immobilized in polymers or liposome-based carriers, we highlight the potential challenges and obstacles that may affect phage stability and bioavailability and limit the successful outcome of therapy. This review serves to enhance the understanding of the integration of materials engineering with clinical practice and production standardization, to address these issues. Additionally, a clear knowledge of the bacteriophage and pharmacokinetics of phage preparations is necessary to implement safe and efficacious bacteriophage treatment in the era of antimicrobial resistance. Full article

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15 pages, 1191 KB

Open AccessArticle

Protective Effects of Neutral Lipids from Phaeodactylum tricornutum on Palmitate-Induced Lipid Accumulation in HepG2 Cells: An In Vitro Model of Non-Alcoholic Fatty Liver Disease

by Marion Peyras, Rose-Marie Orhant, Giuliana Parisi, Cecilia Faraloni, Graziella Chini Zittelli, Vincent Blanckaert and Virginie Mimouni

Molecules 2026, 31(2), 323; https://doi.org/10.3390/molecules31020323 (registering DOI) - 17 Jan 2026

Abstract

Non-alcoholic fatty liver disease (NAFLD), often associated with obesity, has become a serious public health matter. NAFLD is characterized by an excessive lipid accumulation in hepatocytes, mainly stored as triglycerides. The marine microalga Phaeodactylum tricornutum is well known for its richness of bioactive [...] Read more.

Non-alcoholic fatty liver disease (NAFLD), often associated with obesity, has become a serious public health matter. NAFLD is characterized by an excessive lipid accumulation in hepatocytes, mainly stored as triglycerides. The marine microalga Phaeodactylum tricornutum is well known for its richness of bioactive compounds, particularly lipids. Therefore, different natural lipid extracts from P. tricornutum are deciphered to jugulate or prevent obesity leading to NAFLD. In this study, the main focus was on the effects of purified neutral and polar lipid extracts from P. tricornutum in a cellular model of NAFLD. Human HepG2 cells were used and exposed for 24 h to 250 μM palmitate to induce NAFLD with or without microalgal lipid extracts. Data showed that neutral lipid extract presented lower viability and cytotoxic activities on HepG2 at 75 µg/mL. The impact on apoptosis was around 5% and below the threshold. Nevertheless, the use of neutral lipid at 50 µg/mL induced a decrease in the number and size of lipid droplets, and so, preventing NAFLD. On the contrary, the polar lipid extract had no effect on the accumulation of triglycerides in HepG2 cells. To conclude, neutral lipid extract seemed to be a good candidate to prevent NAFLD. Full article

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

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15 pages, 1640 KB

Open AccessArticle

Formulation and Characterization of Hydrogel Chitosan–Pectin Active Films Containing Silymarin

by Svetla Dyankova, Nadya Bozakova, Vanya Boneva, Ayten Solak and Veselin Ivanov

Molecules 2026, 31(2), 322; https://doi.org/10.3390/molecules31020322 (registering DOI) - 17 Jan 2026

Abstract

Silymarin—a standardized extract from the seeds of milk thistle (Silybum marianum L. Gaertn.)—is mainly used for the treatment of hepatitis and other liver diseases. In recent years, the attention of researchers has been directed to its use in dermatology and wound treatment. [...] Read more.

Silymarin—a standardized extract from the seeds of milk thistle (Silybum marianum L. Gaertn.)—is mainly used for the treatment of hepatitis and other liver diseases. In recent years, the attention of researchers has been directed to its use in dermatology and wound treatment. Despite the promising results, there are still many unresolved issues in this area. The aim of the present study is to develop and characterize hydrogel chitosan–pectin films containing silymarin as an active ingredient with potential medical application. Six variants of hydrogel films (control and silymarin-loaded) were obtained from chitosan and pectin solutions by the casting method and analyzed in terms of their physicochemical, structural, mechanical and optical properties, as well as the in vitro dissolution profile of silymarin. The highest tensile strength was measured for the chitosan-based films—23.35 ± 1.74 MPa (control) and 22.01 ± 2.67 MPa (silymarin-loaded), while the barrier properties to UV and visible light were the strongest for chitosan–pectin films with silymarin. The antioxidant potential of the films was determined by DPPH assay and it was found that the variants with silymarin have over 20 times higher antioxidant activity (from 2.020 ± 0.048 to 2.106 ± 0.190 mg TE/g) than the corresponding controls. The results showed that chitosan–pectin films with incorporated silymarin could find application as potential hydrogel dressings in the therapy of wounds and superficial burns. Full article

(This article belongs to the Special Issue Natural Extracts for Pharmaceutical Applications)

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23 pages, 3599 KB

Open AccessArticle

Antioxidant Intervention in NAFLD: Astaxanthin and Kokum Modulate Redox Status and Lysosomal Degradation

by Natalia Ksepka, Natalia Kuzia, Sara Frazzini, Luciana Rossi, Małgorzata Łysek-Gładysińska, Michał Ławiński and Artur Jóźwik

Molecules 2026, 31(2), 321; https://doi.org/10.3390/molecules31020321 (registering DOI) - 16 Jan 2026

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants—astaxanthin and Garcinia indica (kokum)—in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders. Full article

(This article belongs to the Special Issue Antioxidant, and Anti-Inflammatory Activities of Natural Plants)

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46 pages, 1615 KB

Open AccessReview

Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer’s Disease

by Przemysław Niziński, Karolina Szalast, Anna Makuch-Kocka, Kinga Paruch-Nosek, Magdalena Ciechanowska and Tomasz Plech

Molecules 2026, 31(2), 320; https://doi.org/10.3390/molecules31020320 (registering DOI) - 16 Jan 2026

Abstract

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are becoming more prevalent and still lack effective disease-modifying therapies (DMTs). However, translational efficiency remains critically low. For example, a ClinicalTrials.gov analysis of AD programs [...] Read more.

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are becoming more prevalent and still lack effective disease-modifying therapies (DMTs). However, translational efficiency remains critically low. For example, a ClinicalTrials.gov analysis of AD programs (2002–2012) estimated ~99.6% attrition, while PD programs (1999–2019) achieved an overall success rate of ~14.9%. In vitro platforms are assessed, ranging from immortalized neuronal lines and primary cultures to human-induced pluripotent stem cell (iPSC)-derived neurons/glia, neuron–glia co-cultures (including neuroinflammation paradigms), 3D spheroids, organoids, and blood–brain barrier (BBB)-on-chip systems. Complementary in vivo toxin, pharmacological, and genetic models are discussed for systems-level validation and central nervous system (CNS) exposure realism. The therapeutic synthesis focuses on AD, covering symptomatic drugs, anti-amyloid immunotherapies, tau-directed approaches, and repurposed drug classes that target metabolism, neuroinflammation, and network dysfunction. This review links experimental models to translational decision-making, focusing primarily on AD and providing a brief comparative context from other NDDs. It also covers emerging targeted protein degradation (PROTACs). Key priorities include neuroimmune/neurovascular human models, biomarker-anchored adaptive trials, mechanism-guided combination DMTs, and CNS PK/PD-driven development for brain-directed degraders. Full article

(This article belongs to the Special Issue Small Molecule Drug Discovery and Development to Face Neurodegenerative Threads)

21 pages, 4972 KB

Open AccessArticle

Trichostatin A Influences Dendritic Cells’ Functions by Regulating Glucose and Lipid Metabolism via PKM2

by Xiaoyu Yang, Lihui Men, Yan Guo, Linnan Duan, Meiyi Yu, Leyi Zhang, Tongtong Song, Xiang Li and Xia Chen

Molecules 2026, 31(2), 319; https://doi.org/10.3390/molecules31020319 - 16 Jan 2026

Abstract

Dendritic cells (DCs) play a crucial role in immune protection against myocardial infarction (MI). Through multiple experimental methods including bioinformatics, qPCR, Western blotting, immunofluorescence, MTT assays, echocardiography, TTC staining, and flow cytometry, this study found that metabolism was demonstrated to be markedly altered [...] Read more.

Dendritic cells (DCs) play a crucial role in immune protection against myocardial infarction (MI). Through multiple experimental methods including bioinformatics, qPCR, Western blotting, immunofluorescence, MTT assays, echocardiography, TTC staining, and flow cytometry, this study found that metabolism was demonstrated to be markedly altered under oxygen–glucose deprivation (OGD) conditions in DCs. Pyruvate kinase M2 (PKM2) is a key protein in metabolism, and PKM2 was upregulated under OGD conditions in DCs. Trichostatin A (TSA) alleviated the OGD-induced cellular damage in DCs. Furthermore, TSA was shown to modulate DCs’ function by enhancing glycolysis while suppressing fatty acid synthesis and oxidation pathways. The metabolic changes caused by TSA and OGD were mechanistically mediated by PKM2. Mechanistically, PKM2 modulates glucose and lipid metabolism via its dimer formation. These results deepen our understanding of the interplay among TSA, glucose and lipid metabolism and DC functions in MI. Full article

(This article belongs to the Special Issue Nutritional Components of Non-Animal Origin Foods: Structure, Synthesis, Functions and Mechanisms)

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11 pages, 1734 KB

Open AccessArticle

Click Chemistry-Enabled Parallel Synthesis of N-Acyl Sulfonamides and Their Evaluation as Carbonic Anhydrase Inhibitors

by Oleksii V. Gavrylenko, Bohdan V. Vashchenko, Vasyl Naumchyk, Bohdan S. Sosunovych, Oleksii Chuk, Oleksii Hrabovskyi, Olga Kuchuk, Alla Pogribna, Sergiy O. Nikitin, Anzhelika I. Konovets, Volodymyr S. Brovarets, Sergey A. Zozulya, Dmytro S. Radchenko, Oleksandr O. Grygorenko and Yurii S. Moroz

Molecules 2026, 31(2), 318; https://doi.org/10.3390/molecules31020318 - 16 Jan 2026

Abstract

A synthetically accessible library of N-acyl sulfonamides was constructed using a combination of copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) and N-acylation of primary sulfonamides. The proposed two-step reaction sequence had a high experimentally confirmed synthetic success rate (up to 85%) and gave reasonable [...] Read more.

A synthetically accessible library of N-acyl sulfonamides was constructed using a combination of copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) and N-acylation of primary sulfonamides. The proposed two-step reaction sequence had a high experimentally confirmed synthetic success rate (up to 85%) and gave reasonable product yields (up to 61%). As a result of the validation process, a 262-member compound library (out of >70K accessible combinations) was prepared. Biological profiling of the synthesized library by differential scanning fluorimetry and enzymatic assays identified several low micromolar inhibitors of human carbonic anhydrase. The interaction of the discovered hits with the biological target was studied by docking and molecular dynamics. Full article

(This article belongs to the Special Issue Heterocyclic Molecules in Drug Discovery)

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30 pages, 7513 KB

Open AccessArticle

Characterization and Identification of the Ent-Kaurane Diterpenoids in Isodonis Excisoidis Herba Using UHPLC-LTQ-Orbitrap-MS

by Xiaoya Sun, Lingxia Zhang, Conglong Lian, Suiqing Chen, Liping Dai and Yaozu Han

Molecules 2026, 31(2), 317; https://doi.org/10.3390/molecules31020317 - 16 Jan 2026

Abstract

Isodonis Excisoidis Herba (IEH) is a newly discovered herbal medicine used to treat esophageal cancer, chronic pharyngitis, and hepatitis, and ent-kaurane diterpenoids are its main active components. However, systematic studies on the chemical profile of ent-kaurane diterpenoids are lacking. In this study, UHPLC-LTQ-Orbitrap-MS [...] Read more.

Isodonis Excisoidis Herba (IEH) is a newly discovered herbal medicine used to treat esophageal cancer, chronic pharyngitis, and hepatitis, and ent-kaurane diterpenoids are its main active components. However, systematic studies on the chemical profile of ent-kaurane diterpenoids are lacking. In this study, UHPLC-LTQ-Orbitrap-MS was performed to investigate the fragmentation behaviors of three different types of ent-kaurane diterpenoids from IEH. Bridgehead-unsubstituted 7,20-epoxy-ent-kaurane diterpenoids yielded ions with typical losses of R₇H, R₁H, R₁₄H, CH₂O, CO, and R₆H. The [M + NH₄ − NH₃ − R₂₀]⁺ precursor ions at 331.1895 and the characteristic ions at m/z 313.1792, 295.1686, 285.1842, 277.1581, 267.1737, and 249.1632 were the most possible fragmentation pathways for bridgehead-substituted 7,20-epoxy-ent-kaurane diterpenoids. Fragmentation with the successive loss of multiple 18, 42, or 60 Da occurring in the OH groups and OAc groups is characteristic of 7,20-non-epoxy-kaurane diterpenoids. Using accurate mass measurements for each precursor ion and the subsequent fragmented ions, a total of 94 ent-kaurane diterpenoids were identified or tentatively characterized in IEH, including 48 potentially new ent-kaurane diterpenoids. Full article

(This article belongs to the Special Issue The Application of LC-MS in Pharmaceutical Analysis—2nd Edition)

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19 pages, 4459 KB

Open AccessArticle

Rubia cordifolia L. Dichloromethane Extract Ameliorates Contrast-Induced Acute Kidney Injury by Activating Autophagy via the LC3B/p62 Axis

by Xiaoying Sun, Kangxu He, Guanzhong Chen, Xiaoda Yang, Xinhui Pan and Kai Liao

Molecules 2026, 31(2), 316; https://doi.org/10.3390/molecules31020316 - 16 Jan 2026

Abstract

Contrast-induced acute kidney injury (CIAKI) has emerged as the third most prevalent etiology of clinically acquired acute kidney injury, with a lack of specific preventive and therapeutic strategies. Rubia Cordifolia L. (madder root), a medicinal herb with a long-standing history and extensive clinical [...] Read more.

Contrast-induced acute kidney injury (CIAKI) has emerged as the third most prevalent etiology of clinically acquired acute kidney injury, with a lack of specific preventive and therapeutic strategies. Rubia Cordifolia L. (madder root), a medicinal herb with a long-standing history and extensive clinical application, exhibits multiple pharmacological activities. This study aimed to clarify the renal protective effect of Rubia cordifolia L. dichloromethane extract (RCDE) on CIAKI modeling rats and investigate potential anti-apoptotic and autophagy-inducing effects molecular mechanisms. In this study, RCDE constituents were identified by UPLC-Q-TOF-MS. A CIAKI rat model was established to evaluate the nephroprotective effect of RCDE. The results showed that RCDE high-dose group significantly decreased serum SCr and BUN levels, attenuated renal histopathological damage, and modulated oxidative stress markers by decreasing MDA and CAT while increasing SOD, compared with the model group. It downregulated the expressions of Bcl-2, caspase-3 and p62, upregulated the expressions of Bax, Beclin1 and reduced the LC3B-II/LC3B-I ratio in renal tissues. Molecular docking indicates that anthraquinone compounds are probably the principal active constituents of RCDE. This study provides experimental evidence for the intervention efficacy of RCDE against CIAKI. Full article

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18 pages, 1396 KB

Open AccessArticle

Cycloruthenated Imines: A Step into the Nanomolar Region

by Arsenii A. Vasil’ev, Ivan I. Troshin, Pavel G. Shangin, Ksenia M. Voroshilkina, Ilya A. Shutkov, Alexey A. Nazarov and Aleksei V. Medved’ko

Molecules 2026, 31(2), 315; https://doi.org/10.3390/molecules31020315 - 16 Jan 2026

Abstract

A new series of promising and easily accessible antiproliferative agents based on cycloruthenated imines of benzene and thiophene carbaldehydes has been developed and fully characterized using UV-Vis spectroscopy, X-ray diffraction, NMR, HRMS, and cyclic voltammetry. The biological activity of these compounds was tested [...] Read more.

A new series of promising and easily accessible antiproliferative agents based on cycloruthenated imines of benzene and thiophene carbaldehydes has been developed and fully characterized using UV-Vis spectroscopy, X-ray diffraction, NMR, HRMS, and cyclic voltammetry. The biological activity of these compounds was tested against A2780, cisplatin-resistant A2780, and HEK293 cell lines, and they exhibited nanomolar IC₅₀ values. They also showed a selectivity index of up to 2.5, indicating their potential as promising antiproliferative compounds. Full article

(This article belongs to the Section Organometallic Chemistry)

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13 pages, 1254 KB

Open AccessArticle

Synthesis of N-Difluoromethyl Benzothiazole (or Benzoxazole) Selenones as Novel Inhibitors Against Phytopathogenic Fungi

by Zihao Huang, Zhen Liu, Baixin Zhang, Jing Jiao and Ri-Yuan Tang

Molecules 2026, 31(2), 314; https://doi.org/10.3390/molecules31020314 - 16 Jan 2026

Abstract

Azole selenoureas exhibit diverse biological functions. However, the synthesis and biological activity of benzothiazole and benzoxazole selenones remained unexplored. Herein, we report the base-catalyzed synthesis of N-difluoromethyl benzothiazole (or benzoxazole) selenone derivatives, which demonstrated significant antifungal efficacy against Rhizoctonia solani, Phytophthora [...] Read more.

Azole selenoureas exhibit diverse biological functions. However, the synthesis and biological activity of benzothiazole and benzoxazole selenones remained unexplored. Herein, we report the base-catalyzed synthesis of N-difluoromethyl benzothiazole (or benzoxazole) selenone derivatives, which demonstrated significant antifungal efficacy against Rhizoctonia solani, Phytophthora infestans, Botrytis cinerea, and Fusarium oxysporum. Compound 3b exhibited exceptional antifungal activity against R. solani, with an EC₅₀ of 2.10 mg/L. Moreover, it substantially inhibited sclerotia germination (81.5% at 9 mg/L) and formation (79.3% at 9 mg/L), surpassing octhilinone. The protective effect on detached rice leaves and rice seedlings was found to be 43.4% and 85.2% at 100 mg/L, respectively, and 64.4% and 89.4% at 200 mg/L. These findings suggest that benzothiazole and benzoxazole selenones represent promising lead compounds for sustainable plant disease management. Full article

(This article belongs to the Special Issue Nitrogen Containing Heterocyclic Scaffolds: Synthesis and Bioactivity)

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22 pages, 4199 KB

Open AccessArticle

Omics Reveals the Antibacterial Mechanism of Dihydromyricetin and Vine Tea Extract Against Staphylococcus aureus via Cell Wall and Membrane Disruption

by Qiaoni Hui, Ting Li, Keke He, Wei Ma, Ying Guo, Yao Zhang and Liya Song

Molecules 2026, 31(2), 313; https://doi.org/10.3390/molecules31020313 - 16 Jan 2026

Abstract

Staphylococcus aureus (S. aureus) is a common pathogen that threatens healthcare and food safety. Vine tea extract (VTE) and its major active component, dihydromyricetin (DMY), show antibacterial activity. However, their mechanisms of action are not fully understood. In this study, we [...] Read more.

Staphylococcus aureus (S. aureus) is a common pathogen that threatens healthcare and food safety. Vine tea extract (VTE) and its major active component, dihydromyricetin (DMY), show antibacterial activity. However, their mechanisms of action are not fully understood. In this study, we combined proteomics and lipidomics, with RT–qPCR validation of selected differentially expressed genes, to investigate how DMY and VTE affect S. aureus. Proteomics identified 210 and 535 differentially expressed proteins (DEPs) in the DMY-treated and VTE-treated groups, respectively. These DEPs were mainly enriched in cell wall- and membrane-associated pathways. DMY markedly increased proteins involved in fatty acid degradation, glyceride metabolism, and cell wall synthesis. In contrast, VTE increased proteins related to heme/iron acquisition and cell wall degradation. In addition, VTE altered proteins involved in pyrimidine metabolism and aminoacyl-tRNA biosynthesis, suggesting that non-DMY components in VTE may contribute to the antibacterial activity through additional pathways. Lipidomics further indicated membrane lipid remodeling, including increased fatty acid unsaturation and shorter acyl chain length. Collectively, DMY and VTE may inhibit S. aureus growth by remodeling membrane lipids and disturbing cell wall–cell membrane homeostasis. These findings provide mechanistic support for further development of DMY and VTE as natural antimicrobial candidates. Full article

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