Molecules

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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27 pages, 8058 KB

Open AccessArticle

Quality Evaluation and Antioxidant Activity of Cultivated Gentiana siphonantha: An Ethnic Medicine from the Tibetan Plateau

by Jiamin Li, Liyan Zang, Xiaoming Song, Zixuan Liu, Hongmei Li and Jing Sun

Molecules 2026, 31(2), 312; https://doi.org/10.3390/molecules31020312 - 16 Jan 2026

Abstract

Gentiana species are widely used in traditional and modern medicine, and Gentiana siphonantha is an important medicinal representative. To evaluate the quality characteristics of cultivated G. siphonantha roots, the accumulation patterns of iridoid glycosides and antioxidant activities across different cultivation ages and harvest [...] Read more.

Gentiana species are widely used in traditional and modern medicine, and Gentiana siphonantha is an important medicinal representative. To evaluate the quality characteristics of cultivated G. siphonantha roots, the accumulation patterns of iridoid glycosides and antioxidant activities across different cultivation ages and harvest months were investigated. Five major iridoid glycosides were quantified, and antioxidant capacity was assessed through DPPH, ABTS, and FRAP assays. Quality was subsequently multidimensionally evaluated using principal component analysis (PCA), orthogonal partial least squares–discriminant analysis (OPLS-DA), membership function analysis, and entropy weight–TOPSIS analysis, and the relationship between iridoid glycoside content and antioxidant activity was analyzed. Results showed that 3-year-old cultivated roots had the highest total iridoid glycoside content (134.60 mg·g⁻¹ DW), indicating the optimal cultivation age. Peak glycoside accumulation occurred in 4-year-old plants harvested in June–July, identifying this period as the optimal harvest time, as supported by multivariate statistical and comprehensive evaluation. Antioxidant activity increased with cultivation age, with samples collected in June or August showing higher capacities, and it was positively correlated with total iridoid glycoside content, particularly with FRAP (p < 0.05). In conclusion, cultivated G. siphonantha exhibits stable quality and favorable antioxidant activity, providing a basis for standardized cultivation, quality evaluation, and rational utilization. Full article

(This article belongs to the Section Analytical Chemistry)

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21 pages, 1188 KB

Open AccessReview

Antidiabetic and Anti-Inflammatory Potential of Zingiberaceae Plants in Dietary Supplement Interventions

by Natalia Kuzia, Olga Adamska, Natalia Ksepka, Agnieszka Wierzbicka and Artur Jóźwik

Molecules 2026, 31(2), 311; https://doi.org/10.3390/molecules31020311 - 16 Jan 2026

Abstract

Plants from the Zingiberaceae family, particularly Zingiber officinale, Curcuma longa, and Alpinia galanga, are rich sources of bioactive compounds with documented antidiabetic and anti-inflammatory properties. This review summarizes current evidence on their phytochemical profiles and pathways relevant to metabolic regulation. [...] Read more.

Plants from the Zingiberaceae family, particularly Zingiber officinale, Curcuma longa, and Alpinia galanga, are rich sources of bioactive compounds with documented antidiabetic and anti-inflammatory properties. This review summarizes current evidence on their phytochemical profiles and pathways relevant to metabolic regulation. Key compounds, including gingerols, shogaols, curcuminoids, and phenylpropanoids, support glucose homeostasis by enhancing insulin sensitivity, promoting Glucose Transporter Type 4 (GLUT4)-mediated glucose uptake, improving β-cell function, and modulating metabolic signaling pathways such as PI3K/Akt, AMPK, PPARγ, and NF-κB. Their potent antioxidant and anti-inflammatory activities further reduce oxidative stress and chronic low-grade inflammation, both central to the progression of type 2 diabetes and its complications. Evidence from selected clinical and experimental studies suggests that dietary supplementation with whole-rhizome preparations or standardized extracts (including formulation-enhanced products) may improve fasting blood glucose (FBG), glycated hemoglobin (HbA1c), lipid metabolism, and oxidative stress markers. Recent advances in delivery systems, including nanoemulsions, liposomes, and curcumin–piperine complexes, substantially enhance the bioavailability of poorly soluble phytochemicals, strengthening their therapeutic potential. Overall, Zingiberaceae plants emerge as promising natural supplements in nutritional and pharmacological strategies targeting diabetes. Further clinical research is required to refine dosage, confirm long-term efficacy, and support their integration into evidence-based metabolic interventions. Full article

(This article belongs to the Special Issue Chemical Composition and Functional Properties of Food By-Products)

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1 pages, 289 KB

Open AccessCorrection

Correction: Yang et al. Synthesis and Fungicidal Activities of (Z/E)-3,7-Dimethyl-2,6-octadienamide and Its 6,7-Epoxy Analogues. Molecules 2015, 20, 21023–21036

by Mingyan Yang, Hongbo Dong, Jiazhen Jiang and Mingan Wang

Molecules 2026, 31(2), 310; https://doi.org/10.3390/molecules31020310 - 16 Jan 2026

Abstract

In the original publication [...] Full article

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14 pages, 1564 KB

Open AccessArticle

Regioselective Glycosylation of Demethylbellidifolin by Glycosyltransferase AbCGT Yields Potent Anti-Renal Fibrosis Compound

by Limin Zeng, Shichao Cui, Xingyu Ji, Yuhong Liu, Guozhang Long, Yulan Xia, Gang Cheng, Jingya Li and Youhong Hu

Molecules 2026, 31(2), 309; https://doi.org/10.3390/molecules31020309 - 15 Jan 2026

Abstract

Glycosylation serves as an effective strategy to enhance the solubility, bioavailability, and pharmacological activity of polyhydroxyphenols. In this study, we explored the glycosylation of natural and natural-inspired phenolic compounds using the glycosyltransferase AbCGT and evaluated the anti-renal fibrotic potential of the resulting glycosides. [...] Read more.

Glycosylation serves as an effective strategy to enhance the solubility, bioavailability, and pharmacological activity of polyhydroxyphenols. In this study, we explored the glycosylation of natural and natural-inspired phenolic compounds using the glycosyltransferase AbCGT and evaluated the anti-renal fibrotic potential of the resulting glycosides. Among them, 1,3,5,8-tetrahydroxyxanthone 5-O-β-D-glucopyranoside (2-1a), synthesized via the regioselective 5-O-glycosylation of demethylbellidifolin, demonstrated significant anti-renal fibrotic activity. In contrast, its homologous glycosyltransferase, UGT73AE1, predominantly glycosylated demethylbellidifolin at the 3-OH position. Molecular docking studies revealed the structural basis for this regioselectivity difference. To enhance the production of 2-1a, we established a UDP-glucose (UDPG) recycling system by coupling AbCGT with Glycine max sucrose synthase (GmSuSy) and subsequently optimized the reaction conditions. Furthermore, targeted mutagenesis of AbCGT informed by molecular docking analysis identified a F138A mutant that enhanced glycosylation yield by 2.3-fold. This work develops a novel glycosyltransferase-based catalytic system and identifies a new compound with potential anti-renal fibrotic activity. Full article

(This article belongs to the Special Issue Application of Organic Synthesis to Bioactive Compounds, 3rd Edition)

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18 pages, 1305 KB

Open AccessArticle

Varietal Discrimination of Purple, Red, and White Rice Bran Oils Based on Physicochemical Properties, Bioactive Compounds, and Lipidomic Profiles

by Peng Zheng, Yuyue Qin, Xiaoyu Yin, Jianxin Cao, Shujie Wang and Guiguang Cheng

Molecules 2026, 31(2), 308; https://doi.org/10.3390/molecules31020308 - 15 Jan 2026

Abstract

Rice bran oil (RBO) is increasingly valued for its bioactive constituents and associated health benefits. This study presents a comprehensive comparative analysis of RBOs derived from purple (PRBO), red (RRBO), and white (WRBO) rice bran, focusing on their physicochemical properties, fatty-acid profiles, bioactive [...] Read more.

Rice bran oil (RBO) is increasingly valued for its bioactive constituents and associated health benefits. This study presents a comprehensive comparative analysis of RBOs derived from purple (PRBO), red (RRBO), and white (WRBO) rice bran, focusing on their physicochemical properties, fatty-acid profiles, bioactive components, antioxidant activity, oxidative stability, and lipidomics. Our results demonstrate that PRBO consistently exhibited a more favorable fatty-acid composition, characterized by a higher proportion of unsaturated fatty acids and significantly greater concentrations of bioactive compounds (including tocopherols/tocotrienols, γ-oryzanol, phytosterols, and squalene). Accordingly, PRBO showed the highest radical-scavenging activity and storage oxidative stability, followed by RRBO and WRBO. Additionally, untargeted lipidomics using UPLC–MS–MS identified 2908 lipid species spanning 57 subclasses and revealed distinct variety-specific lipid signatures. PRBO was uniquely enriched in lipid species such as ceramide phosphate (CerP) and monogalactosyldiacylglycerol (MGDG). RRBO was characterized by a distinct abundance of sitosteryl esters (SiE), phosphatidic acid (PA), and cardiolipin (CL), while WRBO was distinguished by phosphatidylethanol (PEt), lysodimethylphosphatidylethanolamine (LdMePE), and sphingomyelin (SM). Overall, PRBO possessed not only a broader repertoire of lipid species but also higher relative abundances of nutritionally significant lipids. These results enable quality evaluation and varietal authentication of colored RBOs and guide their targeted use in health-oriented foods and nutritional interventions. Full article

(This article belongs to the Special Issue Novel Food Processing Technologies and Their Effects on Bioactive Components in Foods)

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