Molecules

21 pages, 2059 KB

Open AccessArticle

Synthesis and Biological Evaluation of Curvularin-Type Derivatives with Potential Anti-Inflammatory, Anticancer, and Antimicrobial Activities

by Kyung Hee Kim, Tai Kyoung Kim, Ju-Mi Hong, Jin A Kim, Min Ju Kim, Jin-Hyoung Kim, Joung Han Yim, Il-Chan Kim and Se Jong Han

Molecules 2026, 31(6), 1061; https://doi.org/10.3390/molecules31061061 - 23 Mar 2026

Viewed by 738

Abstract

Curvularins, a class of macrocyclic lactones, have cytotoxic, antimicrobial, and anti-inflammatory properties. Curvularin, a 12-membered macrolactone, was used as a scaffold to design and synthesize structurally modified analogues to investigate structure–activity relationships and improve biological efficacy. Three series of curvularin-based analogues, Cur-5H-OMe, Cur-4P-OMe, [...] Read more.

Curvularins, a class of macrocyclic lactones, have cytotoxic, antimicrobial, and anti-inflammatory properties. Curvularin, a 12-membered macrolactone, was used as a scaffold to design and synthesize structurally modified analogues to investigate structure–activity relationships and improve biological efficacy. Three series of curvularin-based analogues, Cur-5H-OMe, Cur-4P-OMe, and Cur-OMe, were synthesized with the same core structure but different substituent sizes and positions. Nine representative derivatives were evaluated for anti-inflammatory, anticancer, antibacterial, and antifungal activities. In LPS-stimulated RAW 264.7 macrophages, most compounds inhibited nitric oxide (NO) production in a concentration-dependent manner but exhibited cytotoxicity at high concentrations. Cytotoxicity assays against HaCaT cells and human cancer cell lines (HCT116, HeLa, and A375) revealed limited selectivity toward cancer cells. Antimicrobial evaluation indicated selective activity against the Gram-positive bacteria, Staphylococcus aureus. Compound 23 exhibited superior antibacterial potency compared with kanamycin and notable antifungal activity against Candida albicans. This study provides a versatile synthetic platform and identifies key structural features of curvularin derivatives, demonstrating their potential as anti-inflammatory and antimicrobial lead compounds. Full article

(This article belongs to the Special Issue Chemical Constituents and Biological Activities of Natural Sources)

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17 pages, 876 KB

Open AccessArticle

Efficiency Assessment of Fenton-Based Pre-Treatment of Medical Wastewater Using Fe, Cu, and Mn Catalysts—Impact on the Aquatic Environment

by Andrzej R. Reindl, Maciej Tankiewicz, Agnieszka Fiszka Borzyszkowska and Lidia Wolska

Molecules 2026, 31(6), 1060; https://doi.org/10.3390/molecules31061060 - 23 Mar 2026

Cited by 1 | Viewed by 693

Abstract

This study evaluated the efficiency and ecotoxicological impact of the Fenton oxidation process with different metal-based catalysts (FeSO₄, CuSO₄, MnSO₄) in removing pharmaceuticals and organic contaminants from real hospital wastewater. All catalytic systems achieved high oxidation, with [...] Read more.

This study evaluated the efficiency and ecotoxicological impact of the Fenton oxidation process with different metal-based catalysts (FeSO₄, CuSO₄, MnSO₄) in removing pharmaceuticals and organic contaminants from real hospital wastewater. All catalytic systems achieved high oxidation, with COD reduction reaching 81–89% after 4 h. Two complementary approaches were applied: targeted LC-MS/MS quantification of a model mixture of antibiotics and pharmaceuticals, and untargeted GC-MS/MS screening method for assessing the overall organic contaminant profile. Toxicity was assessed using Microtox^®. Targeted analysis showed complete or near-complete degradation of β-lactams, tetracyclines and most sulfonamides, with slightly lower removal for sulfamethoxazole in FeSO₄ system (96%). Fluoroquinolones and selected pharmaceuticals, such as caffeine and propranolol were more resistant, particularly with CuSO₄ and MnSO₄ catalysts. The untargeted GC-MS/MS screening revealed the highest overall reduction in chromatographic peak areas for FeSO₄ (70%), followed by MnSO₄ (39%) and CuSO₄ (36%). GC-MS/MS profiling confirmed that the Fe-catalyzed process was the most effective in reducing the total chromatographic peak area (70%). However, ecotoxicological assays revealed a significant increase in toxicity post-treatment, with growth inhibition of Allivibrio fischeri reaching 98%. This suggests that high oxidation does not directly correlate with biological safety, likely due to the presence of unconsumed reagents or the formation of transformation products with higher acute toxicity. These findings emphasize the necessity of integrating bioassays into treatment evaluation protocols to assess the true environmental risk of treated effluents. Full article

(This article belongs to the Special Issue Potentially Toxic Elements in Contaminated Water: Green Remediation Strategies)

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18 pages, 6653 KB

Open AccessArticle

Pyrene-Chromone Schiff Base Molecules with Tunable Fluorescence: Structure–Property Relationships and Substituent Effects

by Merve Zurnacı

Molecules 2026, 31(6), 1059; https://doi.org/10.3390/molecules31061059 - 23 Mar 2026

Viewed by 783

Abstract

The fluorescence properties of organic molecules are largely determined by molecular architecture, π-conjugation, and electronic substituent effects. In this study, three novel pyrene-chromone Schiff base derivatives were designed and synthesized to investigate substituent-driven modulation of photophysical behavior. The compounds were obtained via condensation [...] Read more.

The fluorescence properties of organic molecules are largely determined by molecular architecture, π-conjugation, and electronic substituent effects. In this study, three novel pyrene-chromone Schiff base derivatives were designed and synthesized to investigate substituent-driven modulation of photophysical behavior. The compounds were obtained via condensation of 1-aminopyrene with three different chromone-based aldehydes and fully characterized by FT-IR, ¹H-NMR, and mass spectrometry. The molecular design involves a donor-π-acceptor architecture: pyrene donates electrons, while the chromene moiety accepts them, enabling charge transfer upon excitation. UV-Vis and fluorescence spectroscopy revealed intense absorption in the 430–440 nm range and tunable emission in the 540–565 nm region, corresponding to large Stokes shifts (107–125 nm). Substituent effects significantly influenced optical band gaps and emission intensities, with the nitro-substituted derivative exhibiting a reduced band gap and pronounced fluorescence quenching due to enhanced intramolecular charge transfer. Concentration-dependent absorption studies demonstrated linear Beer–Lambert behavior, indicating the absence of aggregation within the investigated range. These results establish clear structure–property relationships in pyrene-chromene Schiff bases and highlight their potential as promising candidates for optoelectronic and fluorescence-based sensing applications. Full article

(This article belongs to the Special Issue Advances in Heterocyclic Synthesis, 2nd Edition)

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14 pages, 3217 KB

Open AccessArticle

Optimization of Droplet Granulation Process for HNS-IV Explosives Utilizing Pulsed Air-Jet Shear Technology

by Yuruo Zhang, Jinbo Liu, Peng Zhu and Jingyu Wang

Molecules 2026, 31(6), 1058; https://doi.org/10.3390/molecules31061058 - 23 Mar 2026

Viewed by 612

Abstract

To achieve precise control over droplet size and generation frequency in the granulation process of HNS-IV, this study introduces a novel droplet granulation strategy that utilizes pulsed air-jet shearing technology. This approach enables independent and precise regulation of droplet injection frequency (fg) and [...] Read more.

To achieve precise control over droplet size and generation frequency in the granulation process of HNS-IV, this study introduces a novel droplet granulation strategy that utilizes pulsed air-jet shearing technology. This approach enables independent and precise regulation of droplet injection frequency (fg) and volume (V) through systematic adjustments of air pressure (P), frequency (fp), duty cycle (η), and liquid flow rate (Q). By controlling the suspension flow rate (Q), we successfully achieved primary particle size control, obtaining median particle sizes (D50) of 375.84 μm, 444.45 μm, and 504.22 μm in ascending order. Furthermore, we systematically investigated the influence of calcium alginate (CA) concentration on both the sphericity of the resultant particles and the thermal decomposition characteristics of HNS microspheres. Our findings demonstrate that while increased CA content enhances particle sphericity, it simultaneously affects the thermal decomposition behavior of the microspheres. The proposed pulsed air-jet shearing method offers significant advantages by significantly reducing the accumulation of volatile organic solvents typical of liquid–liquid biphasic systems. Furthermore, the residual non-toxic aqueous solutions can be easily managed, establishing a greener, safer, and highly controllable approach for HNS-IV granulation. This methodology presents a valuable reference for achieving precise and controllable granulation of various energetic materials. Full article

(This article belongs to the Special Issue Optimization of Process Methodology for Specialty and Fine Chemicals)

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17 pages, 2756 KB

Open AccessArticle

Efficient Ultrasound-Assisted Extraction of Four Major Aescins from Aesculi Semen Seeds Using Deep Eutectic Solvents

by Su Bu, Jia Yang, Qifeng Xu, Hui Sun, Xiyu Yang, Xunyong Zhou, Linguo Zhao and Xuhui Zhang

Molecules 2026, 31(6), 1057; https://doi.org/10.3390/molecules31061057 - 23 Mar 2026

Viewed by 628

Abstract

Low extraction efficiency limits the availability and application of aescins, which exhibit various pharmacological activities. Here, we optimized parameters for ultrasound-assisted extraction of aescins from Aesculus chinensis seeds using deep eutectic solvent (DES)-water mixtures. Seven DES formulations were screened, and one providing the [...] Read more.

Low extraction efficiency limits the availability and application of aescins, which exhibit various pharmacological activities. Here, we optimized parameters for ultrasound-assisted extraction of aescins from Aesculus chinensis seeds using deep eutectic solvent (DES)-water mixtures. Seven DES formulations were screened, and one providing the highest yield was selected for optimizing the molar ratio. The effects of four parameters were investigated using single-factor experiments combined with response surface methodology. The optimal extraction conditions were as follows: DES, a 1:1 mixture of 1,3-butanediol and lactic acid, with 42.5% water, used at a liquid-solid ratio of 25 mL/g; ultrasonic frequency, 40 kHz; extraction temperature, 70 °C; and extraction time, 27.5 min. The extraction yield under these conditions was significantly higher than that obtained via traditional methods. Aescin was purified from the DES extract using macroporous resin. AB-8 resin was most efficient in adsorbing aescin in static adsorption tests. Based on dynamic adsorption experiments, optimal separation, with a 100% recovery rate, was achieved by passing four bed volume (BV) of extract through AB-8 column, removing impurities with two BV of deionized water and four BV of 30% ethanol, and eluting with four BV of 60% ethanol at 5–10 mL/min. This green method should be suitable for large-scale applications. Full article

(This article belongs to the Special Issue Advances of Ionic Liquids in Organic, Polymer and Material Chemistry: Key Trends in Green Chemistry: 2nd Edition)

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21 pages, 3189 KB

Open AccessArticle

Cadmium Toxicity Effects on Histone Modifiers, Enzyme Activity and Adipokines in Human Adipose Tissue Cells

by Victor Tadeu Gonçalves Plata, Júlia Fernandes Barcella, Raphael Justa Saran, Artur Francisco da Silva Neto, Yasmin Alaby Martins Ferreira, Andressa Bolsoni-Lopes, Lila Missae Oyama, Lucia Maria Armelin-Correa and Maria Isabel Cardoso Alonso-Vale

Molecules 2026, 31(6), 1056; https://doi.org/10.3390/molecules31061056 - 23 Mar 2026

Viewed by 725

Abstract

Environmental exposure to heavy metals, particularly cadmium (Cd), has been increasingly associated with obesity, metabolic dysfunction, chronic inflammation, and related disorders such as type 2 diabetes and cardiovascular diseases. Adipose tissue (AT), a paracrine and endocrine organ central to systemic energy and inflammatory [...] Read more.

Environmental exposure to heavy metals, particularly cadmium (Cd), has been increasingly associated with obesity, metabolic dysfunction, chronic inflammation, and related disorders such as type 2 diabetes and cardiovascular diseases. Adipose tissue (AT), a paracrine and endocrine organ central to systemic energy and inflammatory homeostasis, is a major site of heavy metal accumulation and a key target of Cd toxicity. However, the mechanisms by which Cd disrupts adipocyte function, especially through epigenetic pathways, remain poorly understood. In this study, we investigated the effects of Cd on epigenetic regulators, antioxidant enzyme activity, inflammatory mediators, and adipogenic programming in human adipose-derived stromal/stem cells (hASCs) and differentiated adipocytes. Cd exposure altered histone modifiers associated with lysine 27 of histone 3 (H3K27), disrupted redox balance in a concentration-dependent manner, impaired adipogenic differentiation and lipid accumulation, and modulated inflammatory and adipokine responses according to differentiation stage and Cd concentration. Our findings suggest that Cd compromises adipose cell homeostasis through mechanisms involving epigenetic dysregulation, oxidative stress imbalance, and altered adipogenic and inflammatory signalling. These observations point to possible long-term metabolic consequences of environmental Cd exposure due to its accumulation in adipose tissue. Full article

(This article belongs to the Section Chemical Biology)

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25 pages, 5007 KB

Open AccessArticle

Molecular Structure, Theoretical NBO Analysis, Vibrational Spectrum of CO₂-Responsive Hydroxyamidine-Based Ionic Liquid: A Combined Computational and Experimental Approach

by Lyazzat Abulyaissova, Nikolay Barashkov, Irina Irgibaeva and Yerbolat Tashenov

Molecules 2026, 31(6), 1055; https://doi.org/10.3390/molecules31061055 - 23 Mar 2026

Cited by 1 | Viewed by 747

Abstract

The utilization and chemical transformation of carbon dioxide remains a pressing problem in modern chemistry. Numerous experimental and theoretical studies have focused on the interaction of CO₂ with amines. In this work, quantum chemical density functional theory (DFT) calculations of equilibrium geometries, [...] Read more.

The utilization and chemical transformation of carbon dioxide remains a pressing problem in modern chemistry. Numerous experimental and theoretical studies have focused on the interaction of CO₂ with amines. In this work, quantum chemical density functional theory (DFT) calculations of equilibrium geometries, energies, electronic and vibrational characteristics of CO₂-sensitive mono-, di-, tris-hydroxyamidines and their associates were carried out by the B3LYP/6-31G(d, p) method. The harmonic vibrational frequencies were scaled and compared with the experimental FTIR spectra for supporting wavenumber assignments. Natural bond orbital (NBO) analysis of the atomic charges and charge delocalization was employed to investigate the nature of hydrogen bonding in hydroxyamidine associates. We also used the intrinsically polarizable continuum model (IEFPCM), and the DFT-D3 method was applied to account for dispersion effects during associate formation. Using the 6-311+G(2d, p) basis set for tris-hydroxyamidine, and its adducts, a comparative analysis of the experimental and calculated ¹H NMR spectra was performed. Here, we considered non-trivial sites of carbon dioxide absorption and hydroxyamidine protonation, which, to our knowledge, have hardly been considered by other authors. Present DFT results agree rather well with the experimental data and support new insight into the formation of the PIL structure. Full article

(This article belongs to the Special Issue Computational and Theoretical Insights on Molecular Structure, Solvation, Interactions and New Materials Design, 2nd Edition)

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18 pages, 1064 KB

Open AccessArticle

Ferrocenoylation of Uracil Derivatives: Study of Reaction Regioselectivity and Biological Activity

by Jasmina Lapić, Ivana Kuzman, Ruža Frkanec, Leo Frkanec and Senka Djaković

Molecules 2026, 31(6), 1054; https://doi.org/10.3390/molecules31061054 - 23 Mar 2026

Cited by 1 | Viewed by 623

Abstract

The N-ferrocenoylation of uracil was studied to evaluate regioselectivity and optimise preparation protocols. Regioselectivity was monitored under various reaction conditions, with particular attention paid to the effects of the solvent and the base. Reactions in DMF were regiospecific, yielding only the N [...] Read more.

The N-ferrocenoylation of uracil was studied to evaluate regioselectivity and optimise preparation protocols. Regioselectivity was monitored under various reaction conditions, with particular attention paid to the effects of the solvent and the base. Reactions in DMF were regiospecific, yielding only the N1 product, while reactions in CH₃CN produced both N1 and N1/N3 products, with ratios depending on the reaction conditions. The highest yield of N1/N3-diferrocenoyl uracil was achieved with an extended reaction time of 90 min using uracil and triethylamine. Optimised conditions were applied to C5-uracil derivatives, producing N1 and N1/N3 products. Regioselectivity and N-substitution were confirmed by NMR, and solvent effects were supported by quantum chemical calculations. The resulting ferrocene–pyrimidine conjugates exhibited oxidative and immunomodulatory activity, highlighting their biological potential. Full article

(This article belongs to the Special Issue Ligand Binding to DNA and RNA, 2nd Edition)

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3 pages, 136 KB

Open AccessEditorial

Recent Advances in Functionalized Nanomaterials: Design, Synthesis, Characterization, and Application

by Siyi Cheng

Molecules 2026, 31(6), 1053; https://doi.org/10.3390/molecules31061053 - 23 Mar 2026

Viewed by 582

Abstract

The rapid evolution of nanotechnology has positioned functionalized nanomaterials at the forefront of modern materials science and engineering [...] Full article

(This article belongs to the Special Issue Recent Advances in Functionalized Nanomaterials: Design, Synthesis, Characterization, and Application)

18 pages, 5429 KB

Open AccessArticle

The pH-Driven Distribution and Migration of Phosphate, Fluoride and Metals/Metalloids in Phosphogypsum Stacks: Insights from Southwest China

by Yongliang Sun, Mei Zhang, Dapeng Luo, Quan Long, Weiguang Guo, Jiang Hou, Le Chang, Yuqi Han, Xiaoxi Peng, Yiqian Tao, Hongjin Tong and Hongbin Wang

Molecules 2026, 31(6), 1052; https://doi.org/10.3390/molecules31061052 - 22 Mar 2026

Cited by 2 | Viewed by 1012

Abstract

The long-term accumulation of phosphogypsum (PG) stacks has caused combined pollution of total phosphorus (TP), fluoride (F⁻), metals and metalloids (MMs), posing a severe threat to regional ecological security. To clarify the migration characteristics of pollutants in PG stacks, water leaching [...] Read more.

The long-term accumulation of phosphogypsum (PG) stacks has caused combined pollution of total phosphorus (TP), fluoride (F⁻), metals and metalloids (MMs), posing a severe threat to regional ecological security. To clarify the migration characteristics of pollutants in PG stacks, water leaching experiments and environmental risk assessment were conducted in 21 typical PG stacks in Southwest China. The spatial differentiation and vertical migration characteristics of pollutants under various coverage measures (high-density polyethylene (HDPE) film covering, soil covering, a composite of film–soil covering, and open-air storage) at different pH conditions were systematically analyzed. Results indicated that under open-air stockpiling conditions, the surface accumulation of TP and F⁻ was the most significant among all covering measures, corresponding to the highest environmental risk. In contrast, the membrane–soil composite covering exhibited the optimal inhibitory effect on the surface diffusion of TP and F⁻, but was less effective for metal and metalloid enrichment. Under acidic conditions (pH < 6), the vertical migration capacity of TP, F⁻, and MMs (Cu, Cd, Cr, Pb, and Zn) increased, leading to enrichment in the deep layers of the stack. With the increase in pH, the calcium-mediated precipitation–adsorption effect created a “geochemical barrier”, facilitating the solid-phase fixation of pollutants. A significant positive correlation among pollutants indicates synergistic release and fixation behaviors. In addition, a pH-controlled P-F-MM source-to-sink conceptual model was established, outlining the dissolution, precipitation, adsorption, fixation and re-enrichment pathway from fresh stock to leachate. This work provides insights for optimizing cover designs and pollution control strategies. Full article

(This article belongs to the Special Issue Emerging Contaminants and Their Transformation Products in the Environment: Advanced Analytical Methods for Assessing Ecological and Human Health Impacts)

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42 pages, 3025 KB

Open AccessReview

Polyphenol-Based Nanomedicine: Versatile Platforms for Immune Modulation and Therapeutic Delivery

by Quoc-Viet Le, Trinh K. T. Nguyen, Ngoc-Nhi Phuong, Dai-Phuc Phan Tran, Van-An Duong, Hien V. Nguyen, Phuoc-Quyen Le, Huy Truong Nguyen and Minh-Quan Le

Molecules 2026, 31(6), 1051; https://doi.org/10.3390/molecules31061051 - 22 Mar 2026

Cited by 3 | Viewed by 1695

Abstract

Polyphenols, abundant compounds found in natural sources, exhibit various biological activities, including immunomodulatory properties that can either stimulate or suppress immune responses, making them promising for therapeutic applications. However, their poor solubility, low bioavailability, rapid metabolism, and non-specific distribution require advanced drug delivery [...] Read more.

Polyphenols, abundant compounds found in natural sources, exhibit various biological activities, including immunomodulatory properties that can either stimulate or suppress immune responses, making them promising for therapeutic applications. However, their poor solubility, low bioavailability, rapid metabolism, and non-specific distribution require advanced drug delivery strategies to overcome limitations in clinical translations. Therefore, nano-drug delivery systems have been intensively studied to explore the full therapeutic potential of polyphenols. Distinct from conventional paradigms where polyphenols serve solely as active compounds, this review advances the concept of polyphenol-based nanomedicine as dual-functional platforms: bioactive structural components and intrinsic immune modulators. Recent strategies to improve the loading efficacy of polyphenols, enhance their cellular uptake, prolong circulation, and enhance specific delivery based on those nanocarriers are emphasized. In addition, polyphenol-based nanoparticles, in which polyphenols serve as structural components, were also studied as self-therapeutics or multifunctional nanocarriers for drug delivery. We intensively focus on their immunomodulatory applications and highlight their potential in preclinical as well as clinical settings for the treatment of various diseases and therapeutic purposes, including autoimmune diseases, cancer immunotherapy, vaccination, inflammation, and infectious diseases. Although polyphenol nanoparticle development has made significant advances, there remain challenges in formulation stability, unclear in vivo toxicity profiles, and clinical translation. Further studies on optimizing nanoparticle design and assessing long-term toxicity are necessary to materialize their application. A combination of polyphenol nanoparticles with other immunotherapies may promise a pronounced efficacy and safety profile. Full article

(This article belongs to the Special Issue Advances in Nanomaterials for Biomedical Applications, 2nd Edition)

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14 pages, 1400 KB

Open AccessArticle

Effect of (−)-Epicatechin on Mitochondrial Homeostasis in Skeletal Muscle of Female Obese Rats

by Elena de la C. Herrera-Cogco, Socorro Herrera-Meza, Yuridia Martínez-Meza, Javier Pérez-Durán, Guillermo Ceballos, Enrique Méndez-Bolaina and Nayelli Nájera

Molecules 2026, 31(6), 1050; https://doi.org/10.3390/molecules31061050 - 22 Mar 2026

Viewed by 1263

Abstract

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering [...] Read more.

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. Full article

(This article belongs to the Special Issue Bioactivity of Natural Compounds: From Plants to Humans, 2nd Edition)

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15 pages, 510 KB

Open AccessArticle

Whole-Cell Biocatalysis for the Production of Structurally Diverse Methoxydihydrochalcones: Broad Activity of the Yarrowia Clade

by Paweł Chlipała, Marcelina Mazur, Anna Kancelista, Zbigniew Lazar and Tomasz Janeczko

Molecules 2026, 31(6), 1049; https://doi.org/10.3390/molecules31061049 - 22 Mar 2026

Viewed by 904

Abstract

Whole-cell biocatalysis presents a sustainable and efficient approach for the selective reduction in α,β-unsaturated bonds in flavonoid derivatives. This study investigates the capability of yeast strains from the Yarrowia clade to catalyze the chemoselective reduction of 4′-methoxychalcone (1a) to its dihydro [...] Read more.

Whole-cell biocatalysis presents a sustainable and efficient approach for the selective reduction in α,β-unsaturated bonds in flavonoid derivatives. This study investigates the capability of yeast strains from the Yarrowia clade to catalyze the chemoselective reduction of 4′-methoxychalcone (1a) to its dihydro derivative. All tested strains exhibited similarly high hydrogenation activity, indicating a broadly conserved enoate reductase function within the clade. Among them, Yarrowia lipolytica KCh 71, previously reported and well characterized in the literature, was selected for preparative-scale transformation of a diverse series of synthetic methoxychalcones bearing additional methoxy groups in positions C-2, C-3, C-4, C-5, and C-6 of ring B. All derivatives were effectively converted into the corresponding dihydrochalcones, with yields ranging from 62% to 92%. Among the tested derivatives, the 2′,4′,6′-trimethoxy chalcone (7a) did not undergo biotransformation under our conditions, whereas mono- and di-methoxy derivatives (2a–6a) were efficiently reduced. These results confirm the broad substrate tolerance, high efficiency, and potential scalability of Y. lipolytica KCh 71, supporting its potential as a whole-cell biocatalyst for the sustainable synthesis of bioactive dihydrochalcones. The consistently high hydrogenation activity observed across 21 tested strains suggests the involvement of evolutionarily conserved enoate reductases. Bioinformatic analysis supports that the Yarrowia clade possesses a robust complement of Old Yellow Enzymes (OYE), providing a reliable enzymatic basis for the observed chemoselective reductions. All Yarrowia tested strains showed the same general transformation type, although the extent and rate of conversion differed among strains, and Y. lipolytica KCh 71 was one of the most tolerant. The broad reduction in α,β-unsaturated chalcones is consistent with the action of flavoenzymatic ene-reductases, particularly Old Yellow Enzyme (OYE)–like reductases. Bioinformatic analysis of Yarrowia genomes reveals putative OYE homologs, supporting this mechanistic interpretation, although the specific enzymes were not identified in this study. Full article

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

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21 pages, 3246 KB

Open AccessArticle

Research on the Evolution Law of Electrochemical Impedance Spectral Characteristics of Lithium-Ion Batteries in Different States

by Xiong Shu, Linkai Tan, Wenxian Yang, Konlayutt Punyawudho, Quan Bai and Qiong Wang

Molecules 2026, 31(6), 1048; https://doi.org/10.3390/molecules31061048 - 22 Mar 2026

Cited by 2 | Viewed by 804

Abstract

Lithium-ion batteries (LIBs) are pivotal for energy storage in electric vehicles and renewable systems, but how to effectively monitor their conditions and ensure their operational reliability is still a concern today. This study employs electrochemical impedance spectroscopy (EIS) to systematically investigate the evolution [...] Read more.

Lithium-ion batteries (LIBs) are pivotal for energy storage in electric vehicles and renewable systems, but how to effectively monitor their conditions and ensure their operational reliability is still a concern today. This study employs electrochemical impedance spectroscopy (EIS) to systematically investigate the evolution of impedance characteristics in nickel–cobalt–manganese oxide (NCM) lithium-ion batteries (LIBs) under varying states of charge (SOCs), states of health (SOHs), temperatures, and mechanical compression displacements. Results reveal that higher SOC and temperature reduce impedance by enhancing ion kinetics and interfacial activity, with

R_{c t}

(charge transfer resistance) exhibiting a U-shaped dependence on SOC, minimized at 40–60%. As SOH declines from 100% to 80%,

R_{S E I}

(SEI film resistance) and

R_{c t}

increase progressively, reflecting SEI thickening and electrode degradation. Mechanical compression (0–8 mm) elevates all resistances, particularly

R_{c t}

at high SOC, due to structural deformation and hindered diffusion. DRT (distribution of relaxation times) spectra highlight amplified low-frequency peaks with aging and low SOC, underscoring diffusion limitations. These findings elucidate multi-scale failure mechanisms, from interfacial polarization to structural instability, providing a framework for non-invasive health monitoring and lifetime prediction. Full article

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15 pages, 1329 KB

Open AccessArticle

Tuning Supramolecular Structure in Trimethylglycine Cocrystals: Competition Between Hydrogen and Halogen Bonding upon Cl/Br Substitution

by Andrei V. Churakov, Alexander G. Medvedev, Anastasia V. Shishkina, Nikita E. Frolov and Mikhail V. Vener

Molecules 2026, 31(6), 1047; https://doi.org/10.3390/molecules31061047 - 21 Mar 2026

Cited by 2 | Viewed by 724

Abstract

Two novel cocrystals of zwitterionic trimethylglycine (TMG) with 2,6-dichlorophenol [TMG•2,6-dichlorophenol] (1:1) and 2,6-dibromophenol [TMG•2,6-dibromophenol] (1:2) are synthesized and structurally characterized using single crystal X-ray diffraction. To estimate the energy of various intermolecular interactions, periodic DFT calculations were performed followed by Bader analysis of [...] Read more.

Two novel cocrystals of zwitterionic trimethylglycine (TMG) with 2,6-dichlorophenol [TMG•2,6-dichlorophenol] (1:1) and 2,6-dibromophenol [TMG•2,6-dibromophenol] (1:2) are synthesized and structurally characterized using single crystal X-ray diffraction. To estimate the energy of various intermolecular interactions, periodic DFT calculations were performed followed by Bader analysis of the crystalline electron density. TMG molecules form dimers in [TMG•2,6-dichlorophenol] (1:1). Its supramolecular structure is governed by the primary charge-assisted H-bonds (~60 kJ/mol) and supported by C–H∙∙∙O contacts (~12 kJ/mol). Cl/Br substitution introduces a more potent halogen-bonding donor. The Br∙∙∙O⁻ interaction (~10 kJ/mol) is strong enough to reorganize the packing into a catemeric motif. As a result, TMG molecules form infinite chains in [TMG•2,6-dibromophenol] (1:2). This illustrates that “fine tuning” is not merely about changing distances, but about shifting the entire energy hierarchy of the crystal. Two-dimensional fingerprint diagrams (2D diagrams) obtained from the Hirshfeld surface and Bader’s analysis of the crystalline electron density give significantly different values of the contributions of the H∙∙∙H contacts, 28% vs. 5% respectively. The main reason for this discrepancy is the large number of relatively short intermolecular H∙∙∙H contacts without a critical bond point in trimethylglycine cocrystals. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules—Recent Advances in Computational and Theoretical Chemistry)

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21 pages, 3640 KB

Open AccessArticle

Hypoglycemic Effects of Glehniae Radix Polysaccharides in Female db/db Mice via Modulation of the Gut Microbiota-PPAR Signaling Axis

by Haochen Xu, Hanqing Lin, Hetong Lin, Peng Wu, Fang Zhang and Longhe Yang

Molecules 2026, 31(6), 1046; https://doi.org/10.3390/molecules31061046 - 20 Mar 2026

Viewed by 751

Abstract

Glehniae Radix, the dried root of Glehnia littoralis Fr. Schmidt ex Miq. (Apiaceae), exhibits diverse biological activities. However, research on the hypoglycemic effects of Glehniae Radix polysaccharides (GRPs), particularly in vivo studies clarifying their mechanisms of action, remains limited. This study aimed [...] Read more.

Glehniae Radix, the dried root of Glehnia littoralis Fr. Schmidt ex Miq. (Apiaceae), exhibits diverse biological activities. However, research on the hypoglycemic effects of Glehniae Radix polysaccharides (GRPs), particularly in vivo studies clarifying their mechanisms of action, remains limited. This study aimed to verify the in vivo hypoglycemic activity of crude GRP in a diabetic model and to elucidate its mechanism. GRP was extracted by water extraction and ethanol precipitation, yielding an extraction rate of 38% and a polysaccharide content of 73.48%. Its hypoglycemic effects and mechanisms were investigated in female B6.BKS(D)-Leprdb/J (db/db) mice following daily administration of GRP at doses of 300 and 600 mg/kg for five consecutive weeks. Following GRP administration, mice in the CH group (600 mg/kg) exhibited a mean reduction in fasting blood glucose levels of approximately 40.7% and an improvement in insulin tolerance test (ITT) outcomes by about 28.4%. Additionally, GRP alleviated damage to the liver, kidney, and colon; decreased hepatic total cholesterol (TC) and triglycerides (TGs) by approximately 40.8% and 24.6%, respectively; and increased colonic Zonula Occludens-1 (ZO-1) expression by an average of 49.5%. Mechanistically, GRP significantly upregulated the expression of peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-γ in the liver, while also increasing the abundance of beneficial gut bacteria such as Alistipes and suppressing harmful bacteria including Escherichia-Shigella. Furthermore, GRP activated the galactose metabolism pathway and inhibited abnormal enrichment of the steroid biosynthesis pathway, collectively ameliorating glucose metabolic disorders in female db/db mice via the “gut microbiota–PPAR signaling axis”. In light of these results, GRP exerts significant in vivo hypoglycemic effects by modulating gut microbiota balance and activating the PPAR signaling pathway. Full article

(This article belongs to the Special Issue Back to Nature: Pharmacological Activities of Phytochemicals Isolated from Medicinal Plants)

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18 pages, 2321 KB

Open AccessArticle

Electron Paramagnetic Resonance Study of Radiation-Induced Defects in Ba₃(PO₄)₂

by Henk Vrielinck, Wouter Holvoet, Dominykas Augulis, Eliot Janssens, David Van der Heggen and Dirk Poelman

Molecules 2026, 31(6), 1045; https://doi.org/10.3390/molecules31061045 - 20 Mar 2026

Viewed by 666

Abstract

We report an electron paramagnetic resonance (EPR) study of radiation-induced defects in Ba₃(PO₄)₂, aiming to understand their role in radio-photoluminescence (RPL). Ba₃(PO₄)₂ is a promising host for rare-earth dopants in optical and [...] Read more.

We report an electron paramagnetic resonance (EPR) study of radiation-induced defects in Ba₃(PO₄)₂, aiming to understand their role in radio-photoluminescence (RPL). Ba₃(PO₄)₂ is a promising host for rare-earth dopants in optical and dosimetric applications. We compare the effects of ultraviolet (UV) and X-ray irradiation on the electron trapping by Eu³⁺, as well as the formation of intrinsic defects by radiation in Eu-doped and undoped samples. Both irradiation types generate Eu²⁺ centers with axial symmetry at one specific Ba lattice site, as confirmed by Q-band EPR. Additional EPR signals near

g \approx 2

reveal radiation-induced centers unrelated to Eu dopants. Detailed analysis of X- and Q-band spectra identifies an H⁰ center and two electron-trapping defects, one tentatively assigned to an oxygen vacancy (F-type center). These findings pave the way for understanding the complex defect landscape governing charge trapping and stability in Ba₃(PO₄)₂. Full article

(This article belongs to the Special Issue Applications of EPR Spectroscopy in Various Fields of Scientific Research)

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23 pages, 4916 KB

Open AccessArticle

The Difluoroboranyl-Fluoroquinolone Derivative “7a” Inhibits Bacterial DNA Gyrase and Exhibits Potent Activity Against Ciprofloxacin-Resistant S. aureus In Vitro and In Vivo Using an Acute Pneumonia Model

by Luis Angel Veyna-Hurtado, Hiram Hernández-López, Denisse de Loera, Juan Manuel Vargas-Morales, Martín Muñoz-Ortega, Lorena Troncoso-Vázquez, Alondra Bocanegra-Zapata and Alberto Rafael Cervantes-Villagrana

Molecules 2026, 31(6), 1044; https://doi.org/10.3390/molecules31061044 - 20 Mar 2026

Viewed by 950

Abstract

According to the World Health Organization, antibiotic research remains insufficient, emphasizing the urgent need for new active molecules, particularly against resistant bacteria. Based on known antibacterial scaffolds, new fluoroquinolone derivatives have been synthesized by our research group, including compound 7a, a difluoroboranyl-fluoroquinolone [...] Read more.

According to the World Health Organization, antibiotic research remains insufficient, emphasizing the urgent need for new active molecules, particularly against resistant bacteria. Based on known antibacterial scaffolds, new fluoroquinolone derivatives have been synthesized by our research group, including compound 7a, a difluoroboranyl-fluoroquinolone that previously demonstrated activity against sensitive strains. Methods: The minimum inhibitory (MIC) and bactericidal (MBC) concentrations of compound 7a were determined against Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli. The selective development of ciprofloxacin-resistant S. aureus was induced by reseeding the isolate on seven consecutive days with an antibiotic concentration that was not capable of inhibiting its development. Pharmacokinetic and toxicological properties were predicted using SwissADME, Way2Drug, and molecular docking (AutoDock Vina). In vivo toxicity was evaluated in BALB/c mice through histopathological liver and kidney analysis and serum biochemical markers. The antibacterial efficacy of 7a (80 mg/kg/day) was assessed in a murine pneumonia model induced by ciprofloxacin-resistant S. aureus. DNA gyrase inhibition was confirmed through plasmid electrophoresis assays in E. coli DH5-α cells. Results: Compound 7a exhibited both MIC and MBC values of 0.25 μg/mL, while ciprofloxacin-resistant S. aureus strains did not exhibit a detectable MIC within the concentration range tested (up to 1024 μg/mL). In silico predictions revealed favorable ADME profiles, low toxicity, and strong interaction with DNA gyrase. In vivo, 7a showed no signs of hepatotoxicity or nephrotoxicity and effectively reduced pneumonic tissue to 1.99% in infected mice. Electrophoretic assays confirmed DNA gyrase inhibition consistent with the mechanism of fluoroquinolones. Conclusions: Compound 7a evidenced activity against ciprofloxacin-resistant S. aureus in vitro and reduced infection progression in vivo. It also displays favorable drug-like properties, low predicted toxicity, and DNA gyrase inhibition. Full article

(This article belongs to the Special Issue Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics, 4th Edition)

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20 pages, 3326 KB

Open AccessArticle

Deep Learning-Guided Discovery of Dual Inhibitors of SARS-CoV-2 Entry and 3CL Protease

by Peng Gao, Ivan Pavlinov, Miao Xu, Catherine Z. Chen, Desarey Morales Vasquez, Qi Zhang, Yihong Ye, Luis Martinez-Sobrido, Wei Zheng and Min Shen

Molecules 2026, 31(6), 1043; https://doi.org/10.3390/molecules31061043 - 20 Mar 2026

Viewed by 918

Abstract

The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for antivirals that are resilient to resistance. Current Food and Drug Administration (FDA)-approved therapies primarily target single viral mechanisms, leaving gaps in efficacy. Here, we developed a Deep Learning-based [...] Read more.

The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for antivirals that are resilient to resistance. Current Food and Drug Administration (FDA)-approved therapies primarily target single viral mechanisms, leaving gaps in efficacy. Here, we developed a Deep Learning-based Activity Screening Model (DLASM), which integrates graph convolutional network with machine learning to identify SARS-CoV-2 inhibitors, using experimental 3-chymotrypsin-like (3CL) main protease assay data. The optimized DLASMs virtually screened ~170,000 compounds from diverse in-house collections and yielded novel hits, several of which not only inhibited the 3CL protease but also blocked viral entry by interfering with heparan sulfate-mediated host interactions. These activities were validated through multiple assays, including 3CL enzymatic inhibition, SARS-CoV-2 pseudotyped particle entry, α-synuclein fibril uptake as a proxy for endocytosis, live virus cytopathic effect, heparan sulfate-dependent entry assay, and a 3D human lung mucociliary tissue model. Molecular docking studies elucidated binding modes at the 3CL protease active site, while molecular dynamics simulations provided insights into compound–heparan sulfate interactions. The identified compounds represent early-stage hits with moderate potency that demonstrate dual-mechanism antiviral activity. Together, these findings establish dual-target inhibition as a promising antiviral strategy, offering not only enhanced potency but also reduced risk of resistance. Moreover, our DLASM framework provides a generalizable pipeline for identifying chemically diverse scaffolds and for broader applications beyond SARS-CoV-2. Full article

(This article belongs to the Section Medicinal Chemistry)

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20 pages, 1615 KB

Open AccessArticle

Angiogenesis Suppression via VEGF–VEGFR2 Inhibition and Stromal–Endothelial Crosstalk Disruption by Myrosinase-Activated Broccoli Extract

by Irina Naletova, Alfonsina La Mantia, Giuseppe Antonio Malfa, Simone Bianchi, Donata Arena, Valeria Di Domenico, Francesco Attanasio, Claudia Di Giacomo and Barbara Tomasello

Molecules 2026, 31(6), 1042; https://doi.org/10.3390/molecules31061042 - 20 Mar 2026

Viewed by 812

Abstract

Dysregulated angiogenesis is involved in cancer and numerous ischemic, autoimmune and inflammatory diseases, prompting extensive research that has yielded a growing array of angiogenesis-modulating molecules used in clinical practice. The dietary phytocomplex of Cruciferous vegetables exhibits multiple biological activities in both in vitro [...] Read more.

Dysregulated angiogenesis is involved in cancer and numerous ischemic, autoimmune and inflammatory diseases, prompting extensive research that has yielded a growing array of angiogenesis-modulating molecules used in clinical practice. The dietary phytocomplex of Cruciferous vegetables exhibits multiple biological activities in both in vitro and in vivo models. However, the impact of a myrosinase-activated broccoli extract (MaBE) on angiogenesis, as well as on stromal–endothelial interactions governing endothelial cell behavior, has not yet been explored. We investigated the effects of MaBE on endothelial–stromal crosstalk using endothelial cells (HUVECs) and fibroblasts (HFF1) both individually and in a fibroblast-conditioned medium model. MaBE dose-dependently inhibited endothelial viability, migration and tube formation, key steps of angiogenesis, through interference with the VEGF–VEGFR2 axis. Notably, MaBE also markedly suppressed HFF1-driven HUVEC migration and capillary-like structure formation, likely through the inhibition of fibroblast motility and the downregulation of VEGF and angiogenin signaling in HFF1 cells. Overall, these findings provide new insight into MaBE regulation of pro-angiogenic behaviors in both endothelial cells and fibroblasts while disrupting their functional interplay. By targeting multiple cellular compartments and key mediators involved in angiogenesis, MaBE emerges as a promising bioactive extract with potential relevance for the management of pathological angiogenesis-related disorders. Full article

(This article belongs to the Special Issue Advances in Extraction, Biological Activity of Natural Products and Their Derivatives)

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22 pages, 2263 KB

Open AccessArticle

Acridinium Chemiluminogenic Labels—Synthesis, Analytical Performance, and Mechanism of Light Generation—A Comparison in View of Biomedical Diagnostics

by Karol Krzymiński, Beata Zadykowicz, Justyna Czechowska, Paweł Rudnicki-Velasquez, Illia Serdiuk, Adam K. Sieradzan and Lucyna Holec-Gąsior

Molecules 2026, 31(6), 1041; https://doi.org/10.3390/molecules31061041 - 20 Mar 2026

Viewed by 1073

Abstract

This paper presents the synthesis, physicochemical characterisation, and analytical applications of chemiluminescent (CL) labels based on acridinium salts (ALs) for biomedical diagnostics. These compounds emit light as a result of oxidative reactions and represent an established class of reagents widely employed in chemiluminescence [...] Read more.

This paper presents the synthesis, physicochemical characterisation, and analytical applications of chemiluminescent (CL) labels based on acridinium salts (ALs) for biomedical diagnostics. These compounds emit light as a result of oxidative reactions and represent an established class of reagents widely employed in chemiluminescence immunochemical assays (CLIAs) today. A series of structurally differentiated acridinium labels (AL1–AL5) was synthesised applying mostly original synthetic routes and purified to chromatographic purity (>90%, RP-HPLC). The compounds, including a commercial product treated as a reference, were successfully conjugated to anti-human IgG, yielding stable immunochemical reagents suitable for immunoassays with CL detection. The chemiluminescence properties of the obtained labels and their protein conjugates were investigated in aqueous buffers and in the presence of surfactants. The emission profiles exhibited characteristic flash-type kinetics with emission maxima occurring within 0.15–0.25 s after reaction initiation. The presence of surfactants more or less significantly enhanced the emission intensity, with signal increases of up to approx. 2-fold compared to surfactant-free systems. Analytical calibration demonstrated a linear response of signal derived from native labels over at least one order of magnitude of concentration, with detection limits falling in the range of 10⁻⁹–10⁻¹⁰ M, confirming the high sensitivity of the developed compounds. The experimental results were supported by theoretical studies using density functional theory (DFT), which confirmed the energetic feasibility of the CL reaction pathway and identified structural factors influencing activation barriers. Additional semiempirical calculations (PM7) indicated that the dielectric environment and proximity of ionic species can influence the reaction energetics, providing mechanistic support for the experimentally observed effects of surfactants. The results demonstrate that both molecular structure and microenvironment influence CL efficiency and kinetics of the investigated systems. The developed acridinium labels exhibit analytical performance better or comparable to commercial reagents and are fully compatible with standard immunodiagnostic conjugation protocols, confirming their suitability for use in modern chemiluminescent immunoassays. Full article

(This article belongs to the Special Issue Chemiluminescence and Photoluminescence of Advanced Compounds)

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21 pages, 3564 KB

Open AccessArticle

Theoretical Survey of the Intrinsic Reactivity of Functionalized (CH₂=C(R)XH) Enols, Enethiols and Eneselenols: Potential Interstellar Species

by Al Mokhtar Lamsabhi, Otilia Mó, Jean-Claude Guillemin and Manuel Yáñez

Molecules 2026, 31(6), 1040; https://doi.org/10.3390/molecules31061040 - 20 Mar 2026

Viewed by 572

Abstract

The conformational properties and intrinsic reactivity of unsaturated CH₂=C(R)XH systems (R = –H, –CH=CH₂, –C≡CH, –C≡N, –Cl, –phenyl, –cyclopentadienyl, –pyrrole; X = O, S, Se)—namely enols, enethiols, and eneselenols—have been investigated using G4 and CCSD(T) calculations. All compounds exhibit [...] Read more.

The conformational properties and intrinsic reactivity of unsaturated CH₂=C(R)XH systems (R = –H, –CH=CH₂, –C≡CH, –C≡N, –Cl, –phenyl, –cyclopentadienyl, –pyrrole; X = O, S, Se)—namely enols, enethiols, and eneselenols—have been investigated using G4 and CCSD(T) calculations. All compounds exhibit antiperiplanar (ap) and anticlinal (ac)-conformers that are nearly isoenergetic, as their relative stabilities are governed by subtle noncovalent interactions, which are analyzed in detail. Both conformers are therefore expected to coexist in the gas phase, and because the rotational barriers are very low, their interconversion is effectively barrierless under typical conditions. In contrast, the corresponding protonated species display significantly higher barriers, approximately three to five times larger. The keto–enol tautomerization involves activation barriers exceeding 180 kJ·mol⁻¹, confirming that, as in other keto–enol rearrangements, the process is not monomolecular. Protonation generally occurs at the methylene carbon, with the exceptions of the –C≡CH and –C≡N derivatives. Strong linear correlations are found among the proton affinities of the three families studied, which follow the trend: enols > enethiols > eneselenols. All systems behave as strong carbon bases; some are predicted to be 20–21 orders of magnitude more basic than ketene and 3–5 orders of magnitude more basic than vinylimine in terms of equilibrium constants. Deprotonation preferentially occurs at the X–H group in nearly all cases. The only exception is the cyclopentadienyl-substituted enol, for which deprotonation of the cyclopentadienyl moiety is favored due to enhanced aromatic stabilization of the resulting anion. Overall, acidity increases along the series O < S < Se. Full article

(This article belongs to the Special Issue Quantum-Chemical Studies for Superspecies—in Celebration of Professor Jean-François Gal’s 80th Birthday)

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21 pages, 4268 KB

Open AccessArticle

Epacadostat and Olaparib Synergistically Inhibit the Growth of BRCA-Proficient Triple-Negative Breast Cancer by Suppressing the Expression of BRCA1 and RAD51

by Lei Huang, Ye Yang, Dongxia Duan, Li Dai, Bingxin Zhai and Bingjun Qian

Molecules 2026, 31(6), 1039; https://doi.org/10.3390/molecules31061039 - 20 Mar 2026

Cited by 1 | Viewed by 871

Abstract

Triple-negative breast cancer (TNBC) cells with intact homologous recombination (HR) repair mechanism can survive treatment with Olaparib, which further limits the clinical application of PARP1/2 inhibitors. Previous studies have demonstrated that inhibition of indoleamine 2,3-dioxygenase (IDO) can enhance the sensitivity of human tumor [...] Read more.

Triple-negative breast cancer (TNBC) cells with intact homologous recombination (HR) repair mechanism can survive treatment with Olaparib, which further limits the clinical application of PARP1/2 inhibitors. Previous studies have demonstrated that inhibition of indoleamine 2,3-dioxygenase (IDO) can enhance the sensitivity of human tumor cells to PARP1/2 inhibitors. However, the mechanisms underlying their synergistic effects in the treatment of TNBC remain unclear. Herein, we demonstrate that the combination of Olaparib and Epacadostat significantly reduces the proliferation of BRCA-proficient MDA-MB-231 and MDA-MB-468 cells compared to either monotherapy. Mechanistically, Epacadostat reduces intracellular kynurenine and NAD⁺ levels, thereby sensitizing TNBCs to PARP1/2 inhibition and significantly amplifying Olaparib-induced DNA damage. Furthermore, Epacadostat and Olaparib synergistically increase cellular reactive oxygen species (ROS), leading to DNA oxidative damage and apoptosis. In vivo, Epacadostat and Olaparib significantly suppressed MDA-MB-468 tumor growth compared to the monotherapy groups, while promoting an increase in phosphorylated H2AX. Notably, the dual inhibition of IDO1 and PARP1/2 specifically reduced the expression of HR core genes and proteins, such as BRCA1 and RAD51, which may contribute to impaired DNA-damage repair and increased sensitivity to Olaparib. In summary, targeting both IDO1 and PARP1/2 represents a promising combination therapy for BRCA-proficient TNBC. Full article

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21 pages, 5628 KB

Open AccessArticle

Combined Effects of Low-Density Polyethylene (LDPE), Zn(II), Cu(II), and Metolachlor on Trichoderma harzianum Growth, Oxidative Stress Induction, and Herbicide Degradation

by Anastasiia Kubera, Przemysław Bernat, Sylwia Różalska, Alicja Okrasińska and Mirosława Słaba

Molecules 2026, 31(6), 1038; https://doi.org/10.3390/molecules31061038 - 20 Mar 2026

Viewed by 629

Abstract

The widespread presence of microplastics (MPs), heavy metals, and herbicide residues in agricultural soil raises concerns about their combined effects on soil microorganisms. This study examined the combined impact of Zn(II)/Cu(II), low-density polyethylene (LDPE), and metolachlor (MET) on Trichoderma harzianum IM 7002, a [...] Read more.

The widespread presence of microplastics (MPs), heavy metals, and herbicide residues in agricultural soil raises concerns about their combined effects on soil microorganisms. This study examined the combined impact of Zn(II)/Cu(II), low-density polyethylene (LDPE), and metolachlor (MET) on Trichoderma harzianum IM 7002, a strain isolated from heavily polluted soil in central Poland. Exposure to LDPE and MET alone reduced fungal growth and induced oxidative stress, whereas Zn(II) at a concentration of 5 mM and Cu(II) at a concentration of 2.5 mM stimulated growth and enhanced MET degradation. HPLC MS/MS analysis identified transformation products, confirming active degradation even under co-exposure to LDPE and metals. Notably, simultaneous exposure to MET, LDPE, and Cu(II) (5 mM) increased antioxidant enzyme activity and decreased lipid peroxidation, suggesting a strengthened antioxidant defense and/or partial utilization of reactive oxygen species during MET biotransformation. Pollutant mixtures also caused quantitative shifts in membrane phospholipid composition and a slight increase in membrane permeability, indicating both toxic effects and adaptive membrane remodeling in response to chemical stress. Overall, T. harzianum IM 7002 exhibited high tolerance to complex pollutant mixtures while maintaining herbicide-degradation capacity, highlighting its potential for remediation of contaminated agricultural soils. Full article

(This article belongs to the Special Issue Advances in Environmental Remediation and Wind–Sand Stabilization Materials)

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18 pages, 689 KB

Open AccessArticle

Effect of Addition Levels of By-Product Mixture (Apple Pomace: Red Potato Pulp: Sugar Beet Pulp) on Phytochemical Profile, Antioxidant Activity and Physical Properties of Extruded Corn Snacks

by Rafał Ziobro, Dorota Gumul, Renata Sabat, Anna Wywrocka-Gurgul and Tomasz Zięba

Molecules 2026, 31(6), 1037; https://doi.org/10.3390/molecules31061037 - 20 Mar 2026

Viewed by 638

Abstract

Plant by-products such as apple pomace, potato pulp, and sugar beet pulp can be an excellent source of polyphenols, other phytochemicals and fiber, which is why they can be an excellent addition to snacks. Snacks, on the other hand, contain a lot of [...] Read more.

Plant by-products such as apple pomace, potato pulp, and sugar beet pulp can be an excellent source of polyphenols, other phytochemicals and fiber, which is why they can be an excellent addition to snacks. Snacks, on the other hand, contain a lot of sugar and starch, which increases the risk of metabolic diseases and is unfavorable for diabetics, but after adding the above-mentioned by-products, their nutritional and health-promoting value increases. The aim of the study was to examine the effect of different addition levels of a mixture of by-products on the nutritional composition, phytochemical content, antioxidant activity, and quality of corn snacks. It was found that mixtures of by-products are an excellent addition to corn snacks in order to increase the health benefits of the product, as this additive increases the content of polyphenols, phenolic acids, anthocyanins, dietary fiber, tocopherols, especially α- and γ-tocopherol, as well as phytosterols, including β-sitosterol, stigmasterol, and campesterol. Furthermore, it increases the antioxidant potential of the snacks and the nutritional value of the final product, especially protein and ash content, reducing the starch content. Snacks containing a 20% by-product mixture may be recommended due to their improved nutritional and health-promoting properties and acceptable physical characteristics. Full article

(This article belongs to the Special Issue Bioactive Compounds in Foods and Their By-Products)

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20 pages, 1640 KB

Open AccessArticle

Cinnamon Bark Essential Oil as a Natural Plant Protection Agent: Chemical Profile, Antimicrobial Activity, and Defence Induction

by Elżbieta Gębarowska, Karolina Budek, Martyna Gębarowska, Anna Kmieć and Antoni Szumny

Molecules 2026, 31(6), 1036; https://doi.org/10.3390/molecules31061036 - 20 Mar 2026

Viewed by 1048

Abstract

Ceylon cinnamon (Cinnamomum verum J. Presl) bark essential oil (CBO) represents a promising source of natural bioactive compounds for biological plant protection. For the first time, the antibacterial and antifungal activity of CBO was systematically evaluated against a curated panel of phytopathogenic [...] Read more.

Ceylon cinnamon (Cinnamomum verum J. Presl) bark essential oil (CBO) represents a promising source of natural bioactive compounds for biological plant protection. For the first time, the antibacterial and antifungal activity of CBO was systematically evaluated against a curated panel of phytopathogenic strains (IOR collection), revealing broad-spectrum efficacy across both bacteria and filamentous pathogens. This study evaluated its chemical composition, antimicrobial activity against phytopathogens, effects on bacterial metabolic activity, and its ability to induce plant defence responses. CBO was dominated by cinnamaldehyde, linalool, and eucalyptol. The oil exhibited strong antibacterial activity against Dickeya dadantii, Pectobacterium carotovorum, Pseudomonas syringae, and Xanthomonas hortorum as well as antifungal activity against Fusarium graminearum, F. culmorum, Rhizoctonia solani and Phytophthora cinnamomi. Metabolic assays revealed a marked reduction in bacterial metabolic activity, indicating that CBO disrupts physiological processes and inhibits growth. In planta experiments showed that foliar application of CBO stimulated PAL activity in wheat leaves without visible phytotoxic symptoms. These findings demonstrate a multifunctional mode of action of CBO, combining direct antimicrobial effects with the elicitation of plant defence responses, and support its potential application in sustainable crop protection. Full article

(This article belongs to the Special Issue Advances in Extraction, Biological Activity of Natural Products and Their Derivatives)

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26 pages, 876 KB

Open AccessArticle

Impact of Dry and Rainy Seasons on the Chemical Profile and Antioxidant Activity of Lippia alba Essential Oil

by Rodrigo Dias Alves, João Pedro Bauman Quieregati, Julia Samara Pereira de Souza, Maria Helena Brandão-Silva, Ariana Pereira da Silva, Katia Castanho Scortecci, Jacqueline do Carmo Barreto and Hugo Alexandre Oliveira Rocha

Molecules 2026, 31(6), 1035; https://doi.org/10.3390/molecules31061035 - 20 Mar 2026

Viewed by 704

Abstract

Seasonal environmental conditions can modulate the chemical composition and biological activity of essential oils from medicinal plants. This study investigated the phytochemical profile, antioxidant potential, cytotoxic activity, and cytoprotective effects of Lippia alba essential oils collected during dry and rainy seasons. Gas chromatography [...] Read more.

Seasonal environmental conditions can modulate the chemical composition and biological activity of essential oils from medicinal plants. This study investigated the phytochemical profile, antioxidant potential, cytotoxic activity, and cytoprotective effects of Lippia alba essential oils collected during dry and rainy seasons. Gas chromatography analysis revealed that all samples preserved a citral chemotype. Principal Component Analysis (PCA) confirmed citral as the primary discriminant metabolite, while quantitative seasonal variations were mainly associated with minor oxygenated monoterpenes, particularly geraniol, carvone, and nerolidol. The essential oil obtained during the rainy season (A5T–RS) exhibited significantly higher antioxidant activity, as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, total antioxidant capacity, and hydrogen peroxide scavenging assays. Intracellular reactive oxygen species (ROS) evaluation using the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) method demonstrated that both oils reduced oxidative stress in murine fibroblasts—L929, with enhanced cytoprotective effects observed for A5T–RS. Cytotoxicity assays against non-tumor (murine fibroblast-NIH/3T3, L929, Chinese hamster ovary—CHO-K1) and tumor (human cervical carcinoma—HeLa, and human hepatocellular carcinoma—HepG2) cell lines revealed selective antiproliferative activity, with tumor cells displaying greater sensitivity, particularly to the rainy-season oil. These results demonstrate that seasonal metabolomic modulation enhances the biological performance of L. alba essential oil without altering its chemotypic identity, highlighting the importance of environmental factors in the development of bioactive plant-derived products. Full article

(This article belongs to the Special Issue Chemical Composition and Anti-Inflammatory Activity of Essential Oils, 2nd Edition)

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16 pages, 1079 KB

Open AccessArticle

Insights into Antioxidant Activity and Trace Element Distribution of Aqueous Extract of Silybum marianum Seeds

by Li Quan, Yi-Xiao Wang, Xiu-Lan Cai, En-Chao Zhou, Xue-Wen Guo, Yi-Jun Chen and Hong-Zhen Lian

Molecules 2026, 31(6), 1034; https://doi.org/10.3390/molecules31061034 - 19 Mar 2026

Viewed by 648

Abstract

The purpose of this work is to investigate the binding state of inorganic elements to flavonoid components in aqueous extract of Silybum marianum (SM) seeds, as well as the antioxidant activity of the extract. This study employed reversed-phase high-performance liquid chromatography (RP-HPLC) to [...] Read more.

The purpose of this work is to investigate the binding state of inorganic elements to flavonoid components in aqueous extract of Silybum marianum (SM) seeds, as well as the antioxidant activity of the extract. This study employed reversed-phase high-performance liquid chromatography (RP-HPLC) to separate silymarin flavonoids in boiling water decoction of SM seeds, and collected the post-column effluent in the segments according to the retention time of seven main silymarin flavonoid components. Inductively coupled plasma mass spectrometry (ICP-MS) was subsequently utilized to quantify nine inorganic elements (As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Zn) in the collected HPLC fractions of the decoction. Meanwhile, electron paramagnetic resonance spectroscopy (EPR) was employed to assess the free radical scavenging activity of aqueous extract of SM seeds, using the signal intensity changes of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and DMPO-OH• adducts as quantitative metrics. The results showed that essential trace elements (Cu, Fe, Mn, Zn) mainly existed as inorganic ions or strong polar forms in the tea-like infusion, with weak binding to flavonoid compounds. On the other hand, the aqueous extract exhibited significant •OH scavenging capacity, with a scavenging rate of 95% against •OH generated by continuous 5 min ultraviolet irradiation of H₂O₂ aqueous solution. This study provides experimental evidence for the development of SM as a food–medicine dual-purpose resource, proposing that consumption of SM seed tea represents a facile and effective approach to supplement trace elements and intake silymarin for enhancing endogenous antioxidant defense. Full article

(This article belongs to the Special Issue Natural Compounds in Modern Therapies, 3rd Edition)

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21 pages, 2334 KB

Open AccessReview

Exploring Microalgae as a Novel Resource for Hepatocellular Carcinoma Therapy

by Sik Yoon, Kok Keong Tan, Won Hoon Song, Chang Won Kim, Boon Huat Bay and Sae-Ock Oh

Molecules 2026, 31(6), 1033; https://doi.org/10.3390/molecules31061033 - 19 Mar 2026

Viewed by 1171

Abstract

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality in the world. Although there is an armamentarium of therapeutic options available for HCC therapy, current treatment modalities still face challenges, such as limited effectiveness and resistance to therapy due to inherent intratumoral [...] Read more.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality in the world. Although there is an armamentarium of therapeutic options available for HCC therapy, current treatment modalities still face challenges, such as limited effectiveness and resistance to therapy due to inherent intratumoral heterogeneity. Hence, the development of novel therapeutics is an unmet need. Microalgae possess the ability to provide naturally derived compounds that are attractive for biomedical applications. The multifunctional nature of microalgae, with its unique combination of anticancer metabolites, oxygen-generating capability, and photosensitizing activity, make them a versatile platform for developing next-generation cancer therapeutics. In light of the above, this succinct narrative review highlights the potential biomedical applications of microalgae in cancer therapy, with a focus on HCC. Preclinical studies have shown the significant potential of microalgae as naturally occurring sources of chemopreventive and anticancer agents against HCC. Future directions include the use of biotechnology to enhance the production of microalgal-derived bioactive compounds and the formulation of biocompatible and biodegradable drug–microalgae embolic agents with prolonged release of anticancer drugs, thereby giving rise to synergistic antitumor effects, and their application for the delivery of immune checkpoint inhibitors for immunotherapy in HCC. Overall, microalgae hold considerable promise for advancing innovative therapeutic strategies against HCC. Full article

(This article belongs to the Special Issue Natural Compounds in Modern Therapies, 3rd Edition)

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23 pages, 3289 KB

Open AccessArticle

Prediction of Bandgap and Key Feature Analysis of Lead-Free Double Perovskite Oxides Based on Deep Learning

by Beibei Wang and Juan Wang

Molecules 2026, 31(6), 1032; https://doi.org/10.3390/molecules31061032 - 19 Mar 2026

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Abstract

Lead-free double perovskites possess the capabilities of wide bandgap control, excellent photoelectric performance, and environmental friendliness. They are an ideal alternative system for addressing the heavy metal toxicity of lead-based perovskites and promoting their large-scale application. Precise control of their bandgap is key [...] Read more.

Lead-free double perovskites possess the capabilities of wide bandgap control, excellent photoelectric performance, and environmental friendliness. They are an ideal alternative system for addressing the heavy metal toxicity of lead-based perovskites and promoting their large-scale application. Precise control of their bandgap is key to the green transformation of optoelectronic devices. Bandgap, as a key parameter determining the photoelectric properties of materials, has limitations in traditional experimental determination and DFT calculation methods, such as being time consuming, labour intensive, costly, and difficult to achieve high-throughput screening. Deep learning provides an efficient solution to this problem, but current research has issues such as a single-model architecture and poor interpretability, which cannot effectively support bandgap regulation. This study utilised 2367 valid datasets of lead-free double perovskites sourced from the Materials Project database and relevant literature. Following preprocessing steps, including MinMaxScaler normalisation and Pearson correlation coefficient screening, the dataset was divided into a ratio of 7:1:2. The bandgap prediction capabilities of four models—MLP, deep ensemble learning, PINN, and Transformer—were systematically compared, with feature importance analysed using the SHAP method. The results show that the MLP model performs the best in medium-scale, structured feature prediction. The R² value of the test set is 0.9311, while the MAE, MSE, and RMSE are 0.1915 eV, 0.0975 eV², and 0.3122 eV, respectively. A total of 98% of the test samples have a prediction error of ≤0.4 eV, highlighting the stability of low bandgap systems. The Transformer is more suitable for large-scale, sequential feature prediction, while the MLP has limited generalisation ability for medium-to-high bandgap systems containing elements such as Si and Mg. The SHAP analysis revealed that the five electronic structure descriptors, such as B_HOMO+ and A_LUMO+, are the key influencing factors of the bandgap. The research results are helpful for the high-precision prediction and mechanism explanation of the bandgap of lead-free double perovskites, providing theoretical support for rational material design, performance optimisation, and bandgap-oriented regulation. They also point out the direction for subsequent model improvement. Full article

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Molecules, Volume 31, Issue 6 (March-2 2026) – 147 articles

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