Molecules

21 pages, 1320 KB

Open AccessArticle

The p-Terphenyl and Kavalactone Secondary Metabolites from the Fungus Hydnellum aurantiacum: Isolation and Evaluation of Their Effects on Platelet Activation

by Nikita Pronin, Anastasiia O. Whaley, Andrei Whaley, Vladislav Zhuravlev, Sergey Smirnov, Sergey Volobuev and Stepan Gambaryan

Molecules 2026, 31(12), 2175; https://doi.org/10.3390/molecules31122175 (registering DOI) - 21 Jun 2026

Abstract

Phytochemical analysis of the tooth fungus Hydnellum aurantiacum resulted in the isolation of twenty-two compounds, including two new kavalactone derivatives—methylkavain (1) and aurapyrone (2); seven new p-terphenyl derivatives—ethylatromentin (3), 2-O-benzoylatromentin (4), aurantin ( [...] Read more.

Phytochemical analysis of the tooth fungus Hydnellum aurantiacum resulted in the isolation of twenty-two compounds, including two new kavalactone derivatives—methylkavain (1) and aurapyrone (2); seven new p-terphenyl derivatives—ethylatromentin (3), 2-O-benzoylatromentin (4), aurantin (5), leucohydnelin (6), leucoaurantin (7), hydroxyleucoaurantiacin (8), benzoyltelephantin M (9); and thirteen known p-terphenyls—atromentin (10), aurantiacin (11), telephantin K (12), leucoatromentin (13), telephantin J (14), curtisian A (15), concrescenin B (16), telephantin L (17), dihydroaurantiacin dibenzoate (18), telephantin M (19), sarcodonin α (20), sarcodonin δ (21) and phellodonin (22). The structures were elucidated using spectroscopic methods (UV, NMR, HR-ESI-MS) along with comparison to literature data. All isolated substances, except 8 and 10, affected thrombin-induced human platelet activation at 90 μM: the seven compounds (9, 12, 16, 17, 20, 21, 22) potentiated it, while the remaining ones exhibited inhibitory activity with the strongest antiplatelet effects observed for 4, 5, and 7 (10.6 ± 4.0, 4.3 ± 3.2, 9.6 ± 2.9% of positive control, respectively). These and other p-terphenyl derivatives with antiplatelet activity identified in this study represent promising structures for further investigation into the mechanism of their action. Full article

(This article belongs to the Special Issue Natural Products: Isolation, Analysis and Biological Activity, 3rd Edition)

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18 pages, 37154 KB

Open AccessArticle

Enhanced Phosphate Capture by Thermally Modified Calcium Aluminate Decahydrate: Optimization, Performance and Mechanism

by Peng Cheng, Ruixiang Wang, Yu Liu, Yu Shang, Lei Yang and Yong-Xiang Ren

Molecules 2026, 31(12), 2174; https://doi.org/10.3390/molecules31122174 (registering DOI) - 21 Jun 2026

Abstract

Adsorption is a promising technology for phosphate removal to alleviate eutrophication. In this study, thermally modified calcium aluminate decahydrate (TCAH) was prepared via low-temperature thermal treatment of calcium aluminate decahydrate (CAH₁₀) to develop a cost-effective and high-performance phosphate adsorbent. The optimal [...] Read more.

Adsorption is a promising technology for phosphate removal to alleviate eutrophication. In this study, thermally modified calcium aluminate decahydrate (TCAH) was prepared via low-temperature thermal treatment of calcium aluminate decahydrate (CAH₁₀) to develop a cost-effective and high-performance phosphate adsorbent. The optimal modification temperature was determined to be 120 °C, which reduced the crystallinity of CAH₁₀, enhanced its porosity, and induced the formation of amorphous calcium aluminate phases. Batch adsorption experiments showed that TCAH exhibited a maximum adsorption capacity of 199.80 mg P/g at 25 °C. The adsorption kinetics followed the pseudo-second-order model, while the adsorption isotherms were well fitted by the Redlich–Peterson model. TCAH maintained high removal efficiency over a wide pH range of 3.0–11.0 and showed high selectivity against common coexisting anions. Characterizations using SEM-EDS, XRD, FTIR and XPS suggested that phosphate removal by TCAH was dominated by synergistic amorphous precipitation and inner-sphere complexation. In tests with real phosphorus-releasing liquor derived from excess sludge, TCAH achieved nearly complete phosphate removal at a dosage of 5 g/L within 6 h. Owing to its readily available raw materials, low preparation temperature, and outstanding phosphate capture performance, TCAH is a promising candidate for efficient phosphate capture and recovery from wastewater. Full article

(This article belongs to the Special Issue Adsorption for Potential Environmental Applications)

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15 pages, 4222 KB

Open AccessArticle

An Ultrasensitive Label-Free Aptasensor for Insulin Detection Assisted by Exonuclease III and 2-Aminopurine

by Dongdong Shi, Yanhua He and Guiqin Yan

Molecules 2026, 31(12), 2173; https://doi.org/10.3390/molecules31122173 (registering DOI) - 21 Jun 2026

Abstract

We designed a label-free fluorescent aptasensor assisted by exonuclease III (Exo III) for sensitive insulin (Ins) detection. The method has high sensitivity, anti-interference properties and repeatability. Additionally, the label-free fluorescent aptasensor assisted by Exo III used to detect Ins has not been reported [...] Read more.

We designed a label-free fluorescent aptasensor assisted by exonuclease III (Exo III) for sensitive insulin (Ins) detection. The method has high sensitivity, anti-interference properties and repeatability. Additionally, the label-free fluorescent aptasensor assisted by Exo III used to detect Ins has not been reported on yet. In this study, we connected a modified DNA sequence to the 5′ end of an aptamer, modifying it into a hairpin structure and exposing 11 nucleotides at the 3′ end containing the base adenine (A). The A was substituted with base 2-aminopurine (2AP) to provide a label-free stable hairpin fluorescent probe (2AP-hairpin probe). This strategy took advantage of the high binding affinity of the Ins aptamer and the susceptibility of 2AP to the local base stacking environment. When Ins is added to the detection system, the 2AP-hairpin probe binds to Ins, adopts a folded state, and blocks Exo III’s access to the binding site for cutting DNA. 2AP cannot be released, and the fluorescence of the 2AP-hairpin probe/cDNA/Ins/Exo III system cannot be restored. Ins detection is achieved by comparing changes in the fluorescent intensity before and after adding Ins to the detection system. The detection limit of the aptasensor is as low as 1.62 nM with a linear range of 3–130 nM. Furthermore, it is able to selectively and directly detect Ins in biological fluids, demonstrating significant clinical application value and research significance. Full article

(This article belongs to the Section Analytical Chemistry)

12 pages, 272 KB

Open AccessArticle

From Phenolic Profile to Gut Function: Comparative Effects of Region-Specific Shilajit on Selected Culturable Intestinal Microbial Groups and β-Glucuronidase Activity—A Preliminary Study

by Elham Kamgar, Małgorzata Gumienna, Barbara Górna-Szweda, Miroslava Kačániová, Przemysław Łukasz Kowalczewski and Joanna Zembrzuska

Molecules 2026, 31(12), 2172; https://doi.org/10.3390/molecules31122172 (registering DOI) - 21 Jun 2026

Abstract

Shilajit is a complex natural phytomineral substance whose composition and biological activity may vary depending on geographical origin. This study compared three commercially available Shilajit samples from Russia (S1), Nepal (S2), and Iran (S3) in terms of phenolic acid profile, antimicrobial activity, and [...] Read more.

Shilajit is a complex natural phytomineral substance whose composition and biological activity may vary depending on geographical origin. This study compared three commercially available Shilajit samples from Russia (S1), Nepal (S2), and Iran (S3) in terms of phenolic acid profile, antimicrobial activity, and their effects on selected intestinal microorganisms and β-glucuronidase activity after simulated gastrointestinal digestion. The samples differed markedly in their phenolic composition, with S3 showing the highest total content of the quantified phenolic acids. All samples exhibited antimicrobial activity, although their intensity depended on the microorganism tested. The in vitro digestion model revealed clear sample-dependent effects: S2 showed the lowest net β-glucuronidase activity and the most beneficial modulation of Lactobacillus and Bifidobacterium, whereas S1 exerted the strongest suppressive effect on Escherichia coli. In contrast, S3, despite the richest phenolic profile, showed the highest β-glucuronidase activity. These findings indicate that the biological activity of Shilajit depends not only on the quantified phenolic acids but also on the broader, region-specific chemical matrix of the material. Full article

(This article belongs to the Special Issue Analyses and Applications of Phenolic Compounds in Food—3rd Edition)

36 pages, 17607 KB

Open AccessArticle

In Vitro Antitumor Effects of Melittin Attached to Fe₃O₄ Magnetic Nanoparticles with Synergistic Contribution of Magnetic Hyperthermia

by Alex Câmpian, Ioana Bâldea, Mara Muntean, Cristian Iacoviță and Adrian Florea

Molecules 2026, 31(12), 2171; https://doi.org/10.3390/molecules31122171 (registering DOI) - 20 Jun 2026

Abstract

Melittin (Mel) is a membrane-active peptide with potential anticancer activity, but its direct therapeutic application may be limited by nonspecific toxicity and delivery-related challenges. The study aimed to assess melittin-functionalized magnetic nanoparticles (MNPs-Mel) as a strategy to enhance antitumor activity in Caco-2 cells, [...] Read more.

Melittin (Mel) is a membrane-active peptide with potential anticancer activity, but its direct therapeutic application may be limited by nonspecific toxicity and delivery-related challenges. The study aimed to assess melittin-functionalized magnetic nanoparticles (MNPs-Mel) as a strategy to enhance antitumor activity in Caco-2 cells, with/without magnetic hyperthermia (MH) association. BJ fibroblasts were used as a normal human in vitro cellular model. The effects of free Mel (2.5 µg/mL), MNPs, and MNPs-Mel (50 µg/mL both) + MH (30 min at 355 kHz and 25 kA/m) were assessed using colorimetry (for viability), luminescence (ATP), and spectrophotometry (lactate) following different exposure conditions. The mechanism of apoptosis induction was evaluated by ELISA (caspase 8 and 9 levels). Transmission electron microscopy (TEM) was also used to evaluate nanoparticle morphology and treatment-associated cellular ultrastructural changes. Free Mel reduced viability in both cell lines, with Caco-2 cells showing greater sensitivity at lower concentrations. MNPs (with/without MH) produced limited and less consistent effects, whereas MNPs-Mel significantly reduced Caco-2 viability and ATP levels and increased LDH and caspase 9. MH further enhanced the effects of MNPs-Mel: reduced viability (57–58% of the control at 24 h and 72 h), decreased ATP levels (67% of the control at 24 h and 53% at 72 h), increased LDH levels (206% of the control at 24 h and 301% at 72 h), and induced the mitochondrial apoptotic pathway (caspase 9 increased with 2164% of the control at 72 h). TEM proved the internalization of both MNPs and MNPs-Mel and revealed extensive ultrastructural alterations concerning mitochondria and lysosomes produced by MNPs-Mel, particularly in the Caco-2 cells. These modifications were heavily increased by MNPs-Mel + MH exposure. Overall, these findings demonstrate that Mel functionalization increases the antitumor activity of Mel at lower doses and that MH further potentiates this effect in Caco-2 cells. Full article

(This article belongs to the Special Issue Bee Products: Recent Progress in Health Benefits Studies, 2nd Edition)

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29 pages, 4004 KB

Open AccessReview

Advances in the Isolation and Purification of Fungal Mycotoxins: From Classical Extraction to Precision Strategies

by Larisa E. Botte, Alena N. Alekseeva and Nikita A. Vasilev

Molecules 2026, 31(12), 2170; https://doi.org/10.3390/molecules31122170 (registering DOI) - 20 Jun 2026

Abstract

Mycotoxins are fungal secondary metabolites with dual significance: they threaten health via food contamination yet hold potential as biopesticides. Their isolation from complex matrices remains a critical challenge. This review analyzes classical methods (liquid–liquid extraction, SPE including QuEChERS, chromatography). Traditional techniques suffer from [...] Read more.

Mycotoxins are fungal secondary metabolites with dual significance: they threaten health via food contamination yet hold potential as biopesticides. Their isolation from complex matrices remains a critical challenge. This review analyzes classical methods (liquid–liquid extraction, SPE including QuEChERS, chromatography). Traditional techniques suffer from poor selectivity, multi-step processing, large toxic solvent volumes, and matrix effects. As alternatives, emerging strategies based on rational design are considered: directed cocrystallization, supercritical fluid extraction, smart MOF/COF membranes, and AI integrated with physicochemical modeling. The concept of “precision” extraction enabling prediction of target isolation at the molecular level is developed. Recommendations for standardizing experimental reporting to create machine-readable datasets for neural networks are provided. The review concludes that while most still require experimental validation for mycotoxins, these approaches point toward selective, sustainable mycotoxin isolation technologies for analytical control and pure standard production. Full article

(This article belongs to the Section Natural Products Chemistry)

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26 pages, 2464 KB

Open AccessArticle

Efficient Cr(VI) Removal from Acidic Wastewater by Tannic-Acid/Fe₃O₄-Modified Corn Straw Biochar: Performance and Mechanism

by Xiaohua Shu, Jiayi Xiao, Huimei Shan, Yunquan Liu and Sanxi Peng

Molecules 2026, 31(12), 2169; https://doi.org/10.3390/molecules31122169 (registering DOI) - 20 Jun 2026

Abstract

The problem of chromium contamination, especially Cr(VI), in acidic wastewater has drawn significant attention, requiring effective and sustainable remediation measures. In this study, tannic-acid/Fe₃O₄-modified corn straw biochar (Fe-TA-CSB) is prepared by a grinding-calcination method to remove Cr(VI). The factors [...] Read more.

The problem of chromium contamination, especially Cr(VI), in acidic wastewater has drawn significant attention, requiring effective and sustainable remediation measures. In this study, tannic-acid/Fe₃O₄-modified corn straw biochar (Fe-TA-CSB) is prepared by a grinding-calcination method to remove Cr(VI). The factors influencing the removal effect of Fe-TA-CSB are investigated through static adsorption experiments. The removal mechanism is explored by combining adsorption kinetics, isothermal adsorption, and thermodynamics, as well as characterization methods. The results show that the removal efficiency of Cr(VI) increases with the increase in pH, contact time (t), and solid–liquid ratio (m/v), but decreases with the increase in initial concentration (C₀). Under optimal conditions of TA/Fe₃O₄ mass ratio = 12.5%, pH = 3.0, m/v = 1.0 g/L, and C₀ = 10 mg/L, the removal efficiency value is 94.02%, which is approximately 81.44% after four adsorption–desorption cycles. The adsorption behavior is fitted well by the Sips isotherm model and Elovich kinetics model, suggesting the adsorption process of heterogeneous monolayer chemisorption. The removal mechanism of Cr(VI) by Fe-TA-CSB involves electrostatic interaction with Cr(VI), reduction in Cr(VI) to Cr(III) through C–O and Fe(II), and complexation of reduced Cr(III) with the introduced Fe–O and phenolic hydroxyl groups. Fe-TA-CSB is an environmentally friendly and renewable adsorbent with good potential for the treatment of acidic wastewater. Full article

23 pages, 8623 KB

Open AccessArticle

Integrating In Vitro Bioactivities and In Silico Molecular Evaluation of Tamarix gallica from Western Algeria

by Fatima Kerroum, Salima Douichene, Fatiha Ben Ahmed, Aida Bassedik, Abdeslam Mohamed Dems, Manel Terbeche and Antoni Szumny

Molecules 2026, 31(12), 2168; https://doi.org/10.3390/molecules31122168 (registering DOI) - 20 Jun 2026

Abstract

The genus Tamarix L. includes several species widely used in traditional medicine for their therapeutic properties. This study aims to evaluate the bioactive potential of Tamarix gallica extracts from Western Algeria using an integrated in vitro and in silico approach. GC–MS analysis with [...] Read more.

The genus Tamarix L. includes several species widely used in traditional medicine for their therapeutic properties. This study aims to evaluate the bioactive potential of Tamarix gallica extracts from Western Algeria using an integrated in vitro and in silico approach. GC–MS analysis with BSTFA derivatization was performed to characterize the chemical profile of the methanolic fraction. In addition, total phenolic, flavonoid, and tannin contents were determined in methanolic extracts of leaves and stems. The biological activities were assessed using antioxidant (DPPH, ABTS, β-carotene, FRAP, O-phenanthroline, and cupric reducing assays), antimicrobial, antidiabetic, and anti-Alzheimer in vitro assays. Molecular docking was conducted to evaluate the inhibitory potential of selected flavonoids against α-amylase, acetylcholinesterase, and butyrylcholinesterase. Results revealed a rich metabolite profile dominated by long-chain aliphatic alcohols (including hentriacontan-12-ol), phytosterols (β-sitosterol), fatty acids, phenolic derivatives, and sugar alcohols. The extracts exhibited strong antioxidant activity (IC₅₀ = 1.34 ± 0.43 and 12.32 ± 0.36 μg·mL⁻¹), significant antimicrobial effects against the tested pathogens, and notable antidiabetic and anticholinesterase activities (IC₅₀ = 78.65 ± 1.43 and 98.37 ± 1.07 μg·mL⁻¹). Molecular docking analysis supported these findings, showing strong binding affinities of quercetin and rhamnetin toward the target enzymes. Overall, T. gallica exhibits promising multifunctional bioactivities with potential pharmaceutical relevance. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 5740 KB

Open AccessArticle

Monoterpene-Rich Nanoemulsion from Thymus vulgaris as a Promising Acaricidal Strategy Against Tetranychus mexicanus: Effects on Survival and Fecundity

by Geraldo J. N. Vasconcelos, Raul V. C. Apolinário, Tatiane M. S. Cardoso, Jefferson D. Cruz, Walter S. M. F., Neto, Maria A. Mpalantinos, Jefferson R. A. Silva and Ana Claudia F. Amaral

Molecules 2026, 31(12), 2167; https://doi.org/10.3390/molecules31122167 (registering DOI) - 20 Jun 2026

Abstract

Mounting acaricide resistance in Tetranychus mexicanus (McGregor) (Acari: Tetranychidae), among the most damaging phytophagous mites in tropical and subtropical crops, has intensified the search for botanical alternatives. An oil-in-water nanoemulsion of Thymus vulgaris essential oil (TVEO-NE) was developed and evaluated for lethal and [...] Read more.

Mounting acaricide resistance in Tetranychus mexicanus (McGregor) (Acari: Tetranychidae), among the most damaging phytophagous mites in tropical and subtropical crops, has intensified the search for botanical alternatives. An oil-in-water nanoemulsion of Thymus vulgaris essential oil (TVEO-NE) was developed and evaluated for lethal and sublethal effects on adult females of T. mexicanus. TVEO, composed mainly of thymol (45%) and p-cymene (37%), was formulated by low-energy emulsification yielding stable dispersions (~200 nm; PDI < 0.25; zeta potential of −22.2 mV). At 30.0 mg a.i./mL, TVEO-NE caused 68.3% corrected mortality at 72 h and suppressed fecundity by ~44–52%; vehicle controls exerted only moderate effects, identifying the essential oil as the primary bioactive driver. Morphological examination revealed collapse of female idiosomata and disruption of excretory pellet architecture, corroborating the bioassay data. Molecular docking against a cathepsin L homology model revealed that thymol and p-cymene interact exclusively via hydrophobic contacts and display substantially lower ChemPLP fitness scores than the reference cysteine protease inhibitor E64, indicating weak predicted binding affinity and arguing against enzyme inhibition as the primary mechanism. Taken together, bioassay, morphological, and docking are consistent with supporting membrane partitioning as a plausible primary mode of action, positioning TVEO-based nanoemulsions as promising botanical tools for T. mexicanus management. Full article

(This article belongs to the Special Issue Research on Chemical Composition and Activity of Natural Products, 2nd Edition)

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27 pages, 3796 KB

Open AccessArticle

Antidiabetic and Antioxidant Potential of a New Bisglyceride Derivative Together with Other Compounds from the Root Bark of Pithecellobium dulce: In Vitro and In Silico Studies

by Gertrude Nembot Messah, Peron Bosco Leutcha, Gabrielle Ange Amang à Ngnoung, Guy Roussel Takuissu Nguemto, Brice Junior Edie Enang II, Hamadou Mamoudou, Soh Désiré, William Feudjou Fouatio, Alembert Tiabou Tchinda, Bienvenu Tsakem, Madan Poka, Patrick Hulisani Demana, Mehmet Öztürk, Xavier Siwe Noundou and Yves Oscar Nganso Ditchou

Molecules 2026, 31(12), 2166; https://doi.org/10.3390/molecules31122166 (registering DOI) - 19 Jun 2026

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by chronic hyperglycemia and oxidative stress. Pithecellobium dulce root has long been recognized for its antidiabetic potential; however, its specific bioactive constituents and mechanisms of action remain poorly defined. This study [...] Read more.

Background: Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by chronic hyperglycemia and oxidative stress. Pithecellobium dulce root has long been recognized for its antidiabetic potential; however, its specific bioactive constituents and mechanisms of action remain poorly defined. This study aimed to evaluate the antidiabetic and antioxidant properties of extracts and isolated molecules from P. dulce root bark. Methods: The DCM/MeOH crude extract of P. dulce root bark was fractionated with n-hexane (PDEH) and ethyl acetate (PDAE), followed by chromatographic purification and spectroscopic characterization, yielding seventeen compounds (1–17). The antioxidant activity (DPPH, ABTS, FRAP) and antidiabetic potential of PDEH, PDAE, and 1–17 were assessed in vitro using yeast-derived enzymes and in silico (targeting human α-glucosidase [PDB: 2QLY] and human α-amylase [PDB: 4GQR]). The in vitro α-glucosidase experiments used saccharomyces cerevisiae enzyme, which varies from the human target. Therefore, these results should be taken as preliminary screening data that needs confirmation with human enzymes. Results: Compound 1 was identified as new, while 2 was isolated for the first time from a natural source. The cell-free chemical tests DPPH, ABTS, and FRAP measured antioxidant capability. These tests quantify radical-scavenging and electron-transfer capabilities in vitro and are preliminary chemical screening methods. They do not directly represent biological antioxidant activity in cells or organisms. PDEH demonstrated strong radical scavenging against DPPH (IC₅₀ = 15.30 μg/mL) and ABTS (IC₅₀ = 12.80 μg/mL), while pristriol (16) showed ferric reducing power (EC₅₀ = 4200 μM FeSO₄/g). Enzyme inhibition assays demonstrated activity against α-amylase (IC₅₀ 53.88–112.24 µg/mL; acarbose IC₅₀ = 91.20 µg/mL) and α-glucosidase (IC₅₀ 18.38–136.88 µg/mL; acarbose IC₅₀ = 11.31 µg/mL). Compounds 15, 1, and 2 showed superior activity compared to acarbose for α-amylase, with effect sizes (Cohen’s d) of 2.15, 0.94, and 0.82, respectively, and IC₅₀ values of 53.88, 88.15, and 92.62 µg/mL; for α-glucosidase, IC₅₀ values were 18.38, 39.25, and 36.40 µg/mL, respectively. Docking studies supported these findings, revealing binding energies of −9.08, −8.34, and −7.22 kcal/mol for compounds 1, 2, and 15 with α-amylase, and −10.35 and −9.79 kcal/mol for compounds 1 and 2 with α-glucosidase. ADME profiling further identified 1 and 2 as promising lead candidates for dual-enzyme inhibition. Conclusions: P. dulce root bark represents a potent source of bioactive molecules with both antioxidant and dual-enzyme-inhibitory properties. These findings validate its traditional use and highlight its potential in the development of multitarget therapies for T2DM management. Full article

(This article belongs to the Special Issue Research on Chemical Composition and Activity of Natural Products, 2nd Edition)

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26 pages, 13249 KB

Open AccessReview

Manganese-Based Oxide Cathode Materials for Aqueous Magnesium-Ion Batteries

by Fangyu Xiong, Yixin Li, Xiaolin Zhang, Bo Liu, Yaohong Yang, Guangsheng Huang and Paul K. Chu

Molecules 2026, 31(12), 2165; https://doi.org/10.3390/molecules31122165 (registering DOI) - 19 Jun 2026

Abstract

Aqueous magnesium-ion batteries (AMIBs) are promising for next-generation energy storage technologies due to their high safety, low cost, high theoretical energy density, and environmental friendliness. In particular, manganese-based oxides have attracted much attention due to the abundant resources, high theoretical capacity, and environmental [...] Read more.

Aqueous magnesium-ion batteries (AMIBs) are promising for next-generation energy storage technologies due to their high safety, low cost, high theoretical energy density, and environmental friendliness. In particular, manganese-based oxides have attracted much attention due to the abundant resources, high theoretical capacity, and environmental friendliness. This paper provides a comprehensive overview of manganese-based oxide cathode materials for AMIBs, including the crystal structure, electrochemical performance, optimization strategies, and electrode reaction mechanisms. Meanwhile, recent research progress of AMIB full cells based on Mn-based oxide cathode materials is summarized. Finally, the challenges and future perspectives of Mn-based oxide cathode materials for AMIBs are discussed. This review will provide a valuable reference and source of inspiration for future research of manganese-based oxide cathode materials for AMIBs. Full article

(This article belongs to the Special Issue Emerging Multifunctional Materials for Next-Generation Energy Systems)

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21 pages, 3160 KB

Open AccessArticle

Immunomodulatory Effects of Propolis on Endothelial Cytokine Release

by Anna Kurek-Górecka, Małgorzata Kłósek, Grażyna Pietsz, Radosław Balwierz and Zenon P. Czuba

Molecules 2026, 31(12), 2164; https://doi.org/10.3390/molecules31122164 - 19 Jun 2026

Abstract

Propolis is a natural resinous product with a broad spectrum of biological activities, including immunomodulatory and anti-inflammatory effects. Increasing evidence suggests that propolis may influence pathways involved in tissue remodeling and fibrosis; however, comparative studies evaluating different propolis types in endothelial models remain [...] Read more.

Propolis is a natural resinous product with a broad spectrum of biological activities, including immunomodulatory and anti-inflammatory effects. Increasing evidence suggests that propolis may influence pathways involved in tissue remodeling and fibrosis; however, comparative studies evaluating different propolis types in endothelial models remain limited. Brain microvascular endothelial cells, as a key component of the blood–brain barrier, constitute a relevant in vitro model for studying anti-inflammatory and neurovascular responses under both physiological and pathological conditions. The aim of this study was to compare the effects of Brazilian green propolis (EEP-BRA) and Polish brown propolis extracts (EEP-PL) on the immunological and fibrotic responses of brain microvascular endothelial cells. Human brain microvascular endothelial cells (hCMEC/D3-BBB) were exposed to propolis extracts (EEP-BRA and EEP-PL) under normoxic and hypoxic conditions to reflect diverse microenvironmental states. The analysis focused on the modulation of release of selected cytokines, including IL-10, IL-4, IL-6, IFN-γ, GM-CSF, TNF-α, IL-2, IL-8, and TGF-β, with particular emphasis on TGF-β as a key regulator of fibrosis. Results: Both propolis extracts significantly modulated cytokine production, although their effects differed depending on the origin of the propolis and oxygen conditions. Under the hypoxia condition followed by IFN-α stimulation, EEP-PL-50 was associated with reduced TNF-α (0.54 vs. 3.61 pg/mL; Hedges g = −6.78; large effect size, p > 0.05) and decreased TGF-β1, IL-8 and TGF-β2/β3. EEP-BRA-50 elicited a distinct profile characterized by increased IL-6 (171.58 vs. 27.63 pg/mL; p < 0.001; g = +6.15) and GM-CSF, while reducing TGF-β1. Both extracts preserved viability > 70% (ISO 10993-5). In conclusion, the results demonstrate that EEP-BRA and EEP-PL exert distinct immunomodulatory effects on brain endothelial cells. These findings highlight the importance of propolis origin in determining its biological activity and support its potential application in modulating inflammation and neurovascular responses. Full article

(This article belongs to the Special Issue Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions)

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18 pages, 2270 KB

Open AccessArticle

Brewing-Method-Dependent Changes in the Bioactive Compound Profile and Antioxidant Potential of Coffee Beverages

by Magdalena Sęk, Urszula Cięciel, Małgorzata Tkacz, Sascha Rohn and Michał Halagarda

Molecules 2026, 31(12), 2163; https://doi.org/10.3390/molecules31122163 - 19 Jun 2026

Abstract

Coffee is an important dietary source of bioactive antioxidant compounds contributing to the antioxidant properties of coffee beverages. While brewing affects yield of total antioxidants, it is still not really clear which individual (phenolic) compounds contribute to the antioxidant activity the most. A [...] Read more.

Coffee is an important dietary source of bioactive antioxidant compounds contributing to the antioxidant properties of coffee beverages. While brewing affects yield of total antioxidants, it is still not really clear which individual (phenolic) compounds contribute to the antioxidant activity the most. A method combining chromatographic separation and individual antioxidant evaluation might therefore be useful. This study aimed at evaluating the antioxidant potential of the compounds in coffee beverages using a high-performance liquid chromatography approach directly coupled to the well-known trolox equivalent antioxidative capacity (TEAC) assay (HPLC-onlineTEAC). The study further evaluated the influence of different brewing methods (‘Americano’, ‘V60’, ‘French press’, and ‘cold brew’) on the bioactive compound profile and antioxidant potential of Arabica coffee beverages. The brewing method significantly affected caffeine content, chlorogenic acid composition, total phenolic content (TPC), and antioxidant activity of the analyzed beverages (p < 0.05). Cold brew samples exhibited the highest total radical scavenging activity and concentrations of major caffeoylquinic acid isomers (3-CQA, 4-CQA, and 5-CQA). In contrast, “French-pressed” beverages were characterized by the highest TPC values, while V60 samples generally showed the lowest antioxidant-related parameters. Chlorogenic acids accounted for more than 84% of the total antioxidant potential of all analyzed beverages, whereas monocaffeoylquinic acids represented the dominant fraction responsible for radical-scavenging activity. The results indicate that prolonged low-temperature extraction favors the recovery and preservation of highly reactive chlorogenic acid isomers and contributes to the enhanced antioxidant potential of coffee beverages, beyond the effect of coffee dose alone. Full article

(This article belongs to the Special Issue Bioactive Compounds in Food: Extraction and Characterization)

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43 pages, 1242 KB

Open AccessReview

Machine-Learning-Driven Molecular Design and Structure–Property–Performance Relationships in Pharmaceutical Chemistry

by Aisulu Zh. Kabdraisova, Almagul K. Umbetova, Gulfairuz Zh. Kairalapova, Yuliya A. Litvinenko, Larissa R. Sassykova, Nazym S. Yelibayeva, Gauhar Sh. Burasheva, Aliya E. Berganayeva, Zhanibek S. Assylkhanov, Meruyert D. Dauletova, Dmitriy Yu. Korulkin, Marzhan A. Baiburkutova and Aigerim M. Sadvakas

Molecules 2026, 31(12), 2162; https://doi.org/10.3390/molecules31122162 - 19 Jun 2026

Abstract

This review examines the emerging role of machine learning (ML) in pharmaceutical chemistry, with emphasis on molecular design, synthetic feasibility, and structure–property–performance (SPP) relationships. By enabling pre-synthesis prediction of physicochemical properties, reaction pathways, and pharmaceutical performance, ML can reduce empirical trial-and-error experimentation and [...] Read more.

This review examines the emerging role of machine learning (ML) in pharmaceutical chemistry, with emphasis on molecular design, synthetic feasibility, and structure–property–performance (SPP) relationships. By enabling pre-synthesis prediction of physicochemical properties, reaction pathways, and pharmaceutical performance, ML can reduce empirical trial-and-error experimentation and support more efficient exploration of chemical space. A structured narrative review design with PRISMA-aligned systematic search elements was used to evaluate 101 studies, enabling transparent literature identification, eligibility screening, and thematic synthesis across heterogeneous ML applications in pharmaceutical chemistry. This review examines structure–property relationships (SPRs) and property–performance relationships (PPRs), with emphasis on key pharmaceutical endpoints such as solubility, permeability, stability, dissolution, and bioavailability. An integrated SPP framework is proposed to connect molecular structure, intermediate properties, and final performance outcomes while incorporating retrosynthetic analysis and experimental feedback and closed-loop optimization. Recent frontier developments are also discussed, including molecular foundation models, multimodal language–graph models, diffusion-based molecular generation, E(3)-equivariant models, and MolMIM-like latent-space optimization. This review also covers co-folding and joint ligand–protein modeling, Boltz-2-like affinity prediction, AlphaFold 3-related biomolecular interaction modeling, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. Key limitations include dataset leakage, benchmark inconsistency, assay variability, conformational and protonation-state effects, reproducibility challenges, regulatory constraints, and the gap between computational prediction and prospective experimental validation. Future progress is expected to depend on hybrid physics–ML models, uncertainty-aware prospective validation, autonomous experimentation, explainable artificial intelligence, and sustainability-aware molecular design. Overall, ML is evolving from a predictive tool into a chemically informed decision-support framework for rational, synthesis-aware, and experimentally validated pharmaceutical development. Full article

(This article belongs to the Section Organic Chemistry)

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17 pages, 9247 KB

Open AccessArticle

Voriconazole Activity Against Pichia kudriavzevii: Influence of Glucose Availability and Culture Medium on Growth, Biofilm Formation, and Antifungal Susceptibility

by Marília Toledo Braga, Giulia Nicolle Jácome Cartaxo, Juliene Cristina da Silva Passos, Denilson Nogueira de Moraes, Carlos Alberto-Silva and Maricilia Silva Costa

Molecules 2026, 31(12), 2161; https://doi.org/10.3390/molecules31122161 - 19 Jun 2026

Abstract

Invasive candidiasis remains a major cause of morbidity and mortality worldwide, with increasing relevance of non-Candida albicans species, particularly Pichia kudriavzevii, which is associated with high mortality and intrinsic resistance to fluconazole. This study evaluated the effect of voriconazole (VRC) on [...] Read more.

Invasive candidiasis remains a major cause of morbidity and mortality worldwide, with increasing relevance of non-Candida albicans species, particularly Pichia kudriavzevii, which is associated with high mortality and intrinsic resistance to fluconazole. This study evaluated the effect of voriconazole (VRC) on P. kudriavzevii growth, biofilm formation, and metabolic activity under different nutritional conditions. Planktonic growth and biofilm development were analyzed in Sabouraud dextrose broth (SDB), RPMI-1640, and RPMI-1640 supplemented with glucose (20 g·L⁻¹). Antifungal activity was assessed by optical density (OD₅₇₀) and XTT reduction assays, and biofilm morphology was examined by light microscopy. Glucose consumption was also determined during growth. VRC showed dose-dependent inhibition in SDB, reducing growth and biofilm metabolic activity by up to 94% and 98%, respectively. In contrast, in RPMI-1640, inhibition was significantly lower (≤27% growth and ≤77% biofilm reduction). Glucose supplementation partially restored antifungal susceptibility and increased biofilm metabolic activity. Growth kinetics confirmed VRC-induced delays in proliferation and impaired glucose utilization. These results demonstrate that VRC activity against P. kudriavzevii is strongly dependent on environmental nutrient availability, particularly glucose, which modulates fungal metabolism, biofilm development, and antifungal susceptibility, highlighting the importance of standardized antifungal susceptibility testing conditions and the role of metabolic state in azole efficacy. Full article

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17 pages, 8121 KB

Open AccessArticle

Efficient PET Glycolysis with Suppressed Diethylene Glycol Formation and Beneficial Residue Effects Using an Organic Phosphonate Catalyst

by Xin-Yu Hao, Xing Cao and Yan-Peng Ni

Molecules 2026, 31(12), 2160; https://doi.org/10.3390/molecules31122160 - 19 Jun 2026

Abstract

Glycolysis of poly(ethylene terephthalate) (PET) offers a promising route for chemical recycling, yet conventional homogeneous catalysts often suffer from low selectivity, severe side reactions (especially diethylene glycol, DEG formation), and detrimental metal residues that compromise the quality of recycled products. To address these [...] Read more.

Glycolysis of poly(ethylene terephthalate) (PET) offers a promising route for chemical recycling, yet conventional homogeneous catalysts often suffer from low selectivity, severe side reactions (especially diethylene glycol, DEG formation), and detrimental metal residues that compromise the quality of recycled products. To address these challenges, we herein develop dipotassium phenylphosphonate (PPOA-K) as an efficient homogeneous catalyst for PET glycolysis. Under optimized conditions (1 wt% catalyst, 197 °C, EG/PET mass ratio 3:1, 90 min, atmospheric pressure), PPOA-K achieves 100% PET depolymerization and a high BHET yield of 86.0%, and the reaction follows apparent first-order kinetics with an activation energy of 70.3 kJ·mol⁻¹. Beyond its high catalytic activity, PPOA-K effectively suppresses the acid-catalyzed etherification of ethylene glycol to DEG, a common side reaction that reduces monomer purity and degrades recycled polyester properties. Remarkably, the trace amount of PPOA-K remaining in the recovered BHET (17.3 ppm) is not detrimental; instead, it continues to inhibit DEG formation during repolymerization and acts as a thermal stabilizer, improving the melting point and thermal stability of recycled PET. The advantages of PPOA-K are further demonstrated in a partial (in situ) glycolysis–repolymerization process, where it reduces the DEG content in the final rPET to 1.78% (vs. 2.25% for conventional Zn(OAc)₂), yielding rPET with a higher melting point, higher crystallinity, and better color. This work demonstrates that dipotassium phenylphosphonate uniquely combines high catalytic activity, side reaction suppression, and beneficial residue effects, offering a new catalyst design strategy for high-quality PET recycling. Full article

(This article belongs to the Special Issue Design of Chemically Recyclable Polymers in Sustainable Chemistry: A Minimalist Perspective)

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22 pages, 830 KB

Open AccessArticle

Organ-Specific Phytochemical Profiles, Wound-Healing and Hemostatic Activities of Symphytum officinale Aerial Parts and Roots with Differential Pyrrolizidine Alkaloid Content

by Getter Dolgošev, Yurii M. Kolesnyk, Olha Hancheva, Oleksandr Panasenko, Andrii Kaplaushenko, Roman Shcherbyna, Valdas Jakštas, Vaidotas Žvikas, Ivo Laidmäe, Jyrki Heinämäki, Oleh Koshovyi and Ain Raal

Molecules 2026, 31(12), 2159; https://doi.org/10.3390/molecules31122159 - 18 Jun 2026

Abstract

Wound healing is a complex biological process involving inflammation, hemostasis, and tissue regeneration, and its impairment may delay recovery and lead to clinical complications. Medicinal plants have long been used in traditional medicine to support wound repair and control bleeding. Among these, Symphytum [...] Read more.

Wound healing is a complex biological process involving inflammation, hemostasis, and tissue regeneration, and its impairment may delay recovery and lead to clinical complications. Medicinal plants have long been used in traditional medicine to support wound repair and control bleeding. Among these, Symphytum officinale L. (comfrey) is widely used in European traditional medicine for the treatment of wounds, fractures, and soft tissue injuries. However, the pharmacological basis of these effects and the contribution of different plant organs remain insufficiently understood. The aim of this study was to characterize the phytochemical composition of extracts obtained from different organs of S. officinale and to evaluate their hemostatic and wound-healing activities in vivo, in order to identify the most active plant parts. Extracts from the roots, leaves, and flowers of S. officinale were prepared using solvents of different polarity. Phytochemical composition was analyzed by spectrophotometric assays and UPLC–MS/MS. Hemostatic and wound-healing activities were evaluated in vivo in rats, and cytological analysis of wound exudate was performed. Distinct organ-specific differences in phytochemical composition were observed, with leaf and flower extracts richer in phenolic compounds and amino acids, while root extracts contained higher levels of pyrrolizidine alkaloids. Leaf (S7) and flower (S13) extracts showed the strongest biological activity. S13 accelerated wound healing, achieving complete wound closure by day 10 compared with day 12 in the reference group, while S7 exhibited the most pronounced hemostatic effect, reducing bleeding cessation time to 44.3 s compared with 64.1 s for the reference preparation and 144.3 s for the control group. Cytological analysis indicated reduced inflammation and enhanced fibroblast activity. The findings support the traditional use of S. officinale in wound treatment and highlight the importance of organ-specific phytochemical composition. Aerial parts showed strong wound-healing and hemostatic effects, suggesting their relevance alongside the traditionally used root and supporting the involvement of multiple constituents in the observed biological activity. The study provides new insights into the organ-specific phytochemical composition and biological activity of S. officinale, thereby supporting further research on the therapeutic potential of its aerial parts. Full article

(This article belongs to the Special Issue Research on Chemical Composition and Activity of Natural Products, 2nd Edition)

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21 pages, 47709 KB

Open AccessArticle

A Plant-Derived Flavonoid, Isobavachin, Promotes Osteogenesis and Alleviates Glucocorticoid-Induced Osteoporosis via Modulation of the ESR1-PI3K/Akt Signaling Pathway

by Jingran Cui, Xuting Song, Heran Liu, Zhenhai Cui, Mengmeng Sun, Min He and Meiying Jin

Molecules 2026, 31(12), 2158; https://doi.org/10.3390/molecules31122158 - 18 Jun 2026

Abstract

Background: Glucocorticoid-induced osteoporosis (GIOP) is marked by impaired osteogenesis and reduced bone formation. Isobavachin (IBA), a flavonoid from Psoralea corylifolia, shows multiple potentials in anti-inflammatory and bone metabolism regulations, but its effects against GIOP remain unclear. This study investigated the osteoprotective effects and [...] Read more.

Background: Glucocorticoid-induced osteoporosis (GIOP) is marked by impaired osteogenesis and reduced bone formation. Isobavachin (IBA), a flavonoid from Psoralea corylifolia, shows multiple potentials in anti-inflammatory and bone metabolism regulations, but its effects against GIOP remain unclear. This study investigated the osteoprotective effects and potential mechanism of IBA using zebrafish GIOP model. Methods: osteoprotective effects of IBA was assessed by fluorescence imaging in a prednisolone-induced zebrafish model, following with osteogenic gene expressions measured by RT-qPCR. Potential targets and pathways of IBA was filtered and predicted by network pharmacology, molecular docking, and molecular dynamics (MD) simulations, and finally validated with a pharmacological rescue experiment using a PI3K-specific inhibitor. Results: IBA improved bone mineralization and upregulated osteogenesis-related genes. Network pharmacology identified the PI3K-Akt pathway as a key pathway, with ESR1, GSK3B, MTOR, and CCND1 as core targets. PI3K inhibition attenuated the osteoprotective effects of IBA and suppressed downstream osteogenic gene expression. Conclusions: IBA alleviates GIOP by modulating the ESR1-associated PI3K-Akt signaling pathway and may serve as a multi-target therapeutic candidate for osteoporosis. Full article

(This article belongs to the Special Issue Functional Evaluation of Natural Products Using Traditional, Alternative, and Emerging Animal Models)

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21 pages, 2278 KB

Open AccessArticle

Keap1-Inhibitory Peptides from Ganoderma lucidum Spores: Virtual Enzymolysis, Fragmentomics and Antioxidant Mechanism

by Beibei Chen, Liang He, Qi Huang and Yanbin Wang

Molecules 2026, 31(12), 2157; https://doi.org/10.3390/molecules31122157 - 18 Jun 2026

Abstract

Ganoderma lucidum spores protein (GLSP) holds significant potential for providing antioxidant peptides. We employed in silico enzymatic hydrolysis to generate small peptide fragments by specific proteins. Through fast computer screening and molecular docking with Keap1 receptor, we identified two potential antioxidant peptides, KAF [...] Read more.

Ganoderma lucidum spores protein (GLSP) holds significant potential for providing antioxidant peptides. We employed in silico enzymatic hydrolysis to generate small peptide fragments by specific proteins. Through fast computer screening and molecular docking with Keap1 receptor, we identified two potential antioxidant peptides, KAF (Lys-Ala-Phe) and NDSF (Asn-Asp-Ser-Phe), from 1171 candidates after efficient hydrolysis by pepsin and proteinase K. Molecular docking result showed both of them could bind onto the Leu557, Ala 510 and Val512 of bioactive pockets of Keap1 through hydrogen bonds and NDSF had lower docking energy (−85.6073 kcal/mol). The in vitro antioxidant validation indicated both of them could eliminate DPPH and ABTS radicals dramatically, and NDSF had a stronger scavenging capacity on DPPH (IC₅₀ = 35.1 μg/mL) and ABTS (IC₅₀ = 55.9 μg/mL), respectively. Quantitative chemical analysis further revealed that the key antioxidant active sites of NDSF were located at O18 of Ser amino side chain, and N9 of Lys terminal amino residue for KAF. Furthermore, in the cellular experiments, NDSF and KAF effectively increased the activities of antioxidant enzymes such as SOD, CAT, and GPx, while also reducing the level of MDA. Together, these findings highlight the potential of Ganoderma lucidum spore proteins as a source for the rapid identification of antioxidant peptides. The two selected peptides, therefore, s hold promising prospects for applications in functional foods and health products. Full article

(This article belongs to the Special Issue Advances and Opportunities of Natural Products in Drug Discovery)

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