Molecules

19 pages, 2345 KiB

Open AccessArticle

Linker-Dependent Variation in the Photophysical Properties of Dinuclear 2-Phenylpyridinato(salicylaldiminato)platinum(II) Complexes Featuring NDI Units

by Soichiro Kawamorita, Tatsuya Matsuoka, Kazuki Nakamura, Bijak Riyandi Ahadito and Takeshi Naota

Molecules 2025, 30(12), 2664; https://doi.org/10.3390/molecules30122664 - 19 Jun 2025

Abstract

Through-space charge transfer (TSCT) between spatially adjacent donor and acceptor units has garnered considerable attention as a promising design principle for optoelectronic materials. While TSCT systems incorporating rigid spacers have been extensively studied to enhance through-space interactions, transition metal complexes connected by flexible [...] Read more.

Through-space charge transfer (TSCT) between spatially adjacent donor and acceptor units has garnered considerable attention as a promising design principle for optoelectronic materials. While TSCT systems incorporating rigid spacers have been extensively studied to enhance through-space interactions, transition metal complexes connected by flexible linkers remain underexplored, despite increasing interest in their potential TSCT behavior. Herein, we report the design and synthesis of a donor–acceptor–donor (D-A-D)-type complex (1), in which a central naphthalenediimide (NDI) electron acceptor is linked to 2-phenylpyridinato(salicylaldiminato)platinum(II) complexes via flexible alkyl linkers. By systematically varying the linker length (n = 3, 4, 5, 6; 1a–d), we achieved precise control over the spatial arrangement between the NDI core and the platinum moieties in solution. Notably, compound 1a (n = 3) adopts an S-shaped conformation in solution, giving rise to a distinct TSCT absorption band. The structural and photophysical properties were thoroughly investigated using single-crystal X-ray diffraction, ¹H NMR, NOESY analysis, and DFT calculations, which collectively support the existence of the folded conformation and associated TSCT behavior. These findings highlight that TSCT can be effectively induced in flexible molecular systems by exploiting intramolecular spatial proximity and non-covalent interactions, thereby offering new avenues for the design of responsive optoelectronic materials. Full article

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

17 pages, 2153 KiB

Open AccessArticle

Green Purification of Invertase from Ultrasonicated Sifted Baker’s Yeast by Membrane Filtration: A Comparative Study

by Serap Durakli Velioglu, Ufuk Bagci, Kadir Gurbuz Guner, Haci Ali Gulec and Hasan Murat Velioglu

Molecules 2025, 30(12), 2663; https://doi.org/10.3390/molecules30122663 - 19 Jun 2025

Abstract

This study aimed to produce invertase with characteristics comparable to commercial formulations using a low-cost raw material, employing environmentally friendly extraction and refinement methods. Sifted yeast, the residual baker’s yeast in industrial production, was used as raw material, and invertase in the yeast [...] Read more.

This study aimed to produce invertase with characteristics comparable to commercial formulations using a low-cost raw material, employing environmentally friendly extraction and refinement methods. Sifted yeast, the residual baker’s yeast in industrial production, was used as raw material, and invertase in the yeast cell was extracted by ultrasonication and purified by micro- and ultra-filtration (MF and UF) methods. Subjecting the crude enzyme extract to MF followed by UF resulted in increased activity and specific activity. Through this process, the enzyme activity increased from 153 IU/mL to 691 IU/mL. The purified enzyme was lyophilized and the production of invertase at the laboratory scale was accomplished. The obtained enzyme was found to be stable at pH 5 and within the temperature range of 30–40 °C. It retained its activity for 60 days at −18 °C, whereas a 20% loss in activity was observed at +4 °C over the same period. As a result, it was demonstrated that invertase enzyme can be produced from a low-cost raw material which is considered as waste in the industry. To pass to the commercial production stage, processing of higher amounts of raw material by preventing foaming and heating problems in ultrasonication and scale-up studies testing the permeability properties of different membrane systems at a pilot-scale are necessary. Full article

(This article belongs to the Collection Advances in Food Chemistry)

► Show Figures

Figure 1

15 pages, 3748 KiB

Open AccessArticle

Constructing 1 + 1 > 2 Photosensitizers Based on NIR Cyanine–Iridium(III) Complexes for Enhanced Photodynamic Cancer Therapy

by Ziwei Wang, Weijin Wang, Qi Wu and Dongxia Zhu

Molecules 2025, 30(12), 2662; https://doi.org/10.3390/molecules30122662 - 19 Jun 2025

Abstract

Photosensitizers with high singlet oxygen (¹O₂) generation capacity under near-infrared (NIR) irradiation are essential and challenging for photodynamic therapy (PDT). A simple yet effective molecular design strategy is realized to construct 1 + 1 > 2 photosensitizers with synergistic [...] Read more.

Photosensitizers with high singlet oxygen (¹O₂) generation capacity under near-infrared (NIR) irradiation are essential and challenging for photodynamic therapy (PDT). A simple yet effective molecular design strategy is realized to construct 1 + 1 > 2 photosensitizers with synergistic effects by covalently integrating iridium complexes with cyanine via ether linkages, as well as introducing aldehyde groups to suppress non-radiative decay, named CHO−Ir−Cy. It is demonstrated that CHO−Ir−Cy successfully maintains the NIR absorption and emission originated from cyanine units and high ¹O₂ generation efficiency from the iridium complex part, which gives full play to their respective advantages while compensating for shortcomings. Density functional theory (DFT) calculations reveal that CHO−Ir−Cy exhibits a stronger spin–orbit coupling constant (ξ (S1, T1) = 9.176 cm⁻¹) and a reduced energy gap (ΔE = −1.97 eV) between triplet excited states (T₁) and first singlet excited states (S₁) compared to parent Ir−Cy or Cy alone, directly correlating with its enhanced ¹O₂ production. Remarkably, CHO−Ir−Cy demonstrates superior cellular internalization in 4T1 murine breast cancer cells, generating substantially elevated ¹O₂ yields compared to individual Ir−Cy/Cy under 808 nm laser irradiation. Such enhanced reactive oxygen species production translates into effective cancer cell ablation while maintaining favorable biocompatibility, significant phototoxicity and negligible dark toxicity. This molecular engineering strategy overcomes the inherent NIR absorption limitation of traditional iridium complexes and ensures their own high ¹O₂ generation ability through dye–metal synergy, establishing a paradigm for designing metal–organic photosensitizers with tailored photophysical properties for precision oncology. Full article

(This article belongs to the Special Issue Advances in Coordination Chemistry, 3rd Edition)

► Show Figures

Figure 1

32 pages, 2937 KiB

Open AccessArticle

Enhancing the Pharmacological Properties of Triterpenes Through Acetylation: An Anticancer and Antioxidant Perspective

by Barbara Bednarczyk-Cwynar, Piotr Ruszkowski, Andrzej Günther, Szymon Sip, Katarzyna Bednarek-Rajewska and Przemysław Zalewski

Molecules 2025, 30(12), 2661; https://doi.org/10.3390/molecules30122661 (registering DOI) - 19 Jun 2025

Abstract

This paper presents the influence of acetylation on the cytotoxic and antioxidant activity of natural triterpenes. Oleanolic acid, betulin, betulinic acid and other triterpenes have been modified to improve their pharmacological properties. Acylation of the hydroxyl group at the C-3 position showed significant [...] Read more.

This paper presents the influence of acetylation on the cytotoxic and antioxidant activity of natural triterpenes. Oleanolic acid, betulin, betulinic acid and other triterpenes have been modified to improve their pharmacological properties. Acylation of the hydroxyl group at the C-3 position showed significant changes in biological activity, in particular against cancer cell lines such as HeLa, A-549, MCF-7, PC-3 and SKOV-3, with the highest IC₅₀ results for acetyloleanolic acid (1b) and acetylbetulinic acid (4b). Docking results showed that all compounds tested demonstrated the ability to bind to pockets (C1–C5) of the p53 Y220 protein, obtaining different Vina score values. The strongest binding was observed for compound 2b in the C3 pocket (−10.1 kcal × mol⁻¹), while in the largest C1 pocket, the best result was achieved by compound 5b (−9.1 kcal × mol⁻¹). Moreover, antioxidant studies using the CUPRAC and DPPH tests showed significant differences in the mechanisms of action of the compounds depending on the structure. The analyses of ADMETox confirmed the favorable pharmacokinetic profile and low toxicity of most of the tested derivatives. The results suggest that acetylated triterpenes, especially 1b and 4b, have great potential as anticancer drug candidates, requiring further research on their cytotoxic activity and structural modifications. Full article

(This article belongs to the Special Issue Phytochemistry, Antioxidants, and Anti-Diabetes)

► Show Figures

Graphical abstract

27 pages, 2051 KiB

Open AccessArticle

Electrochemical Assessment of Rhus typhina L. Leaf Extract as a Novel Green Corrosion Inhibitor for OL37 in 1 M HCl Medium

by Denisa-Ioana Răuță (Gheorghe), Florina Brânzoi, Roxana-Doina Truşcă, Sorin-Marius Avramescu and Ecaterina Matei

Molecules 2025, 30(12), 2660; https://doi.org/10.3390/molecules30122660 - 19 Jun 2025

Abstract

This study evaluates the corrosion-inhibiting effects of the methanolic (P₁) and the hydroalcoholic (P₂) extracts of the Rhus typhina L. leaves on carbon steel (OL37) in 1 M HCl. Extracts were prepared with microwave-assisted extraction and characterized using HPLC [...] Read more.

This study evaluates the corrosion-inhibiting effects of the methanolic (P₁) and the hydroalcoholic (P₂) extracts of the Rhus typhina L. leaves on carbon steel (OL37) in 1 M HCl. Extracts were prepared with microwave-assisted extraction and characterized using HPLC and LC-MS. Electrochemical methods (OCP, EIS, PDP) and surface analyses (SEM, EDX) assessed the performance of both extracts. The results showed that the P₁ and P₂ extracts significantly reduced corrosion rates by forming protective layers on the metal surface, with inhibition efficiencies exceeding 90%, at 1000 ppm concentration, for P₁ (93%), for P₂ at 800 ppm (91%) and 1000 ppm (94%). The P₂ extract demonstrated superior long-term performance, maintaining protection after 96 h of immersion. The extracts function as mixed-type inhibitors, affecting both anodic and cathodic reactions, with physicochemical adsorption demonstrated by the Langmuir isotherm. Overall, the Rhus typhina leaf extracts, particularly the P₂ extract, offer a promising, eco-friendly approach to corrosion prevention in acidic environments. Full article

(This article belongs to the Section Electrochemistry)

28 pages, 4548 KiB

Open AccessArticle

New Tools in Heavy Metal Detection: Synthesis, Spectroscopic, and Quantum Chemical Characterization of Selected Water-Soluble Styryl Derivatives of Quinoline and 1,10-Phenanthroline

by Jacek E. Nycz, Jolanta Kolińska, Nataliya Karaush-Karmazin, Tieqiao Chen, Maria Książek and Joachim Kusz

Molecules 2025, 30(12), 2659; https://doi.org/10.3390/molecules30122659 - 19 Jun 2025

Abstract

A series of water-soluble molecules based on 8-isopropyl-2-methyl-5-nitroquinoline and 1,10-phenanthroline core were designed by introducing a π-conjugated bridge, vinyl unit –CH=CH–. We present the selective conversion of methyl groups located on the C2 and C9 positions in the constitution of selected quinoline or [...] Read more.

A series of water-soluble molecules based on 8-isopropyl-2-methyl-5-nitroquinoline and 1,10-phenanthroline core were designed by introducing a π-conjugated bridge, vinyl unit –CH=CH–. We present the selective conversion of methyl groups located on the C2 and C9 positions in the constitution of selected quinoline or 1,10-phenanthroline derivatives, respectively, into vinyl (or styryl) products by applying Perkin condensation. The two groups of ligands differ in the presence of one or two arms. The structure of the molecule ((1E,1′E)-(1,10-phenanthroline-2,9-diyl)bis(ethene-2,1-diyl))bis(benzene-4,1,3-triyl) tetraacetate was determined by single-crystal X-ray diffraction measurements. The X-ray, NMR, and DFT computational studies indicate the influence of rotation (rotamers) on the physical properties of studied styryl molecules. The results show that the styryl molecules with the vinyl unit –CH=CH– exhibit significant static and dynamic hyperpolarizabilities. Quantum chemical calculations using density functional theory and B3LYP/6-311++G(d,p) with Grimme’s dispersion correction approach predict the existence and relative stability of different spatial cis(Z)- and trans(E)-conformers of styryl derivatives of quinoline and 1,10-phenanthroline, which exhibit different electronic distribution and conjugation within the molecular skeleton, dipole moments, and steric interactions, leading to variations in their photophysical behavior and various applications. Our studies indicate that the rotation and isomerization of aryl groups can significantly influence the electronic and optical properties of π-conjugated systems, such as vinyl units (–CH=CH–). The rotation of aryl groups around the single bond that connects them to the vinyl unit can lead to changes in the effective π-conjugation between the aryl group and the rest of the π-conjugated system. The rotation and isomerization of aryl groups in π-conjugated systems significantly impact their electronic and optical properties. These changes can modify the efficiency of π-conjugation, affecting charge transfer processes, absorption properties, light emission, and electrical conductivity. In designing optoelectronic materials, such as organic dyes, organic semiconductors, or electrochromic materials, controlling the rotation and isomerization of aryl groups can be crucial for optimizing their functionality. Full article

(This article belongs to the Special Issue Chemistry and Applications of Compounds Containing Quinoline or Isoquinoline Structure)

► Show Figures

Figure 1

21 pages, 705 KiB

Open AccessArticle

Nicotine Degradation by Trametes versicolor: Insights from Diverse Environmental Stressors and Wastewater Medium

by Bhautik Dave, Ewa Lobos Moysa and Anna Kuźnik

Molecules 2025, 30(12), 2658; https://doi.org/10.3390/molecules30122658 - 19 Jun 2025

Abstract

Nicotine, a major alkaloid in tobacco, poses significant environmental risks due to its persistence in wastewater. This study explores the degradation of naturally extracted nicotine from tobacco leaves by the white-rot fungus Trametes versicolor, aiming to assess its biodegradation capacity under diverse [...] Read more.

Nicotine, a major alkaloid in tobacco, poses significant environmental risks due to its persistence in wastewater. This study explores the degradation of naturally extracted nicotine from tobacco leaves by the white-rot fungus Trametes versicolor, aiming to assess its biodegradation capacity under diverse environmental stressors. Nicotine was extracted using a NaOH–petroleum ether method and confirmed through Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Biodegradation experiments were conducted using potato dextrose broth and synthetic wastewater as growth media under varying pH (2.5 and 5.20) and temperatures (25 °C and 37 °C). Fungal growth and nicotine degradation were monitored through biomass quantification and NMR-based analysis. Optimal degradation occurred at 25 °C and pH 5.20, particularly in synthetic wastewater, suggesting enhanced fungal adaptation in complex media. Degradation efficiency ranged from 80% to 99%, with synthetic wastewater outperforming conventional media. Extreme conditions, such as pH 2.5 at 37 °C, significantly hindered fungal growth. These findings demonstrate T. versicolor’s potential for effective nicotine removal in wastewater and highlight the environmental parameters critical to its performance. This work supports the development of sustainable fungal-based bioremediation strategies for managing nicotine contamination in aquatic environments. Full article

(This article belongs to the Special Issue Biodegradation of Conventional and Emerging Pollutants, 2nd Edition)

32 pages, 1072 KiB

Open AccessReview

Brain Neurotrophins and Plant Polyphenols: A Powerful Connection

by Marco Fiore, Sergio Terracina and Giampiero Ferraguti

Molecules 2025, 30(12), 2657; https://doi.org/10.3390/molecules30122657 - 19 Jun 2025

Abstract

Neurodegenerative disorders, mental conditions, and cognitive decline represent significant challenges worldwide, with growing pieces of evidence implicating alterations in neurotrophin signaling as central to these diseases. Neurotrophins—such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—are indispensable for neuronal survival, differentiation, and [...] Read more.

Neurodegenerative disorders, mental conditions, and cognitive decline represent significant challenges worldwide, with growing pieces of evidence implicating alterations in neurotrophin signaling as central to these diseases. Neurotrophins—such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—are indispensable for neuronal survival, differentiation, and synaptic plasticity, and their dysregulation is closely associated with various neuropathological situations. Similarly, dietary plant polyphenols, abundant in vegetables, fruits, wine, tea, and extra virgin olive oil, show powerful anti-inflammatory, antioxidant, and anti-apoptotic activities. This narrative review critically addresses the evolving body of evidence that links plant polyphenols and brain neurotrophins, emphasizing several molecular mechanisms by which polyphenols regulate and modulate neurotrophin signaling. Crucial pathways include mitigation of neuroinflammatory responses, activation of intracellular cascades such as the cAMP response element-binding protein (CREB), epigenetic modulation, and the diminution of oxidative stress. Together, these effects contribute to potentiated enhanced synaptic function, neuronal integrity, and better learning and memory processes. Moreover, this narrative review examines how polyphenol-induced upregulation of neurotrophins may alleviate conditions associated not only with neurodegeneration but also with addiction and mood disorders, suggesting extensive therapeutic approaches. Findings from clinical investigations and animal models are presented to sustain the neuroprotective role of polyphenol-rich diets. Lastly, future research directions are recommended, focusing on polyphenol bioavailability optimization, considering combinatory dietary stratagems, and proposing personalized nutritional interventions. This wide-ranging perspective highlights plant polyphenols as encouraging modulators of neurotrophin pathways and supports their inclusion in approaches aimed at promoting brain health and counteracting neurodegenerative decline. Full article

(This article belongs to the Special Issue Exploring the Natural Antioxidants in Foods)

18 pages, 16058 KiB

Open AccessArticle

Surface-Confined Self-Assembly of Star-Shaped Tetratopic Molecules with Vicinal Interaction Centers

by Jakub Lisiecki and Damian Nieckarz

Molecules 2025, 30(12), 2656; https://doi.org/10.3390/molecules30122656 - 19 Jun 2025

Abstract

Precise control over the morphology of surface-supported supramolecular patterns is a significant challenge, requiring the careful selection of suitable molecular building blocks and the fine-tuning of experimental conditions. In this contribution, we demonstrate the utility of lattice Monte Carlo computer simulations for predicting [...] Read more.

Precise control over the morphology of surface-supported supramolecular patterns is a significant challenge, requiring the careful selection of suitable molecular building blocks and the fine-tuning of experimental conditions. In this contribution, we demonstrate the utility of lattice Monte Carlo computer simulations for predicting the topology of adsorbed overlayers formed by star-shaped tetratopic molecules with vicinal interaction centers. The investigated tectons were found to self-assemble into a range of structurally diverse architectures, including two-dimensional crystals, aperiodic mosaics, Sierpiński-like aggregates, and one-dimensional strands. The theoretical insights presented herein deepen our understanding of molecular self-assembly and may aid in the rational design of novel nanomaterials with tunable porosity, chirality, connectivity, and molecular packing. Full article

(This article belongs to the Special Issue Molecular Self-Assembly in Interfacial Chemistry)

► Show Figures

Graphical abstract

22 pages, 2364 KiB

Open AccessArticle

Design and Synthesis of Fluorescence-Labeled TAK779 Analogs as Chemical Probes

by Hiroyuki Konno, Takuya Saito, Taichi Aota, Daiki Takanuma, Mizuho Okuyama and Chikako Yokoyama

Molecules 2025, 30(12), 2655; https://doi.org/10.3390/molecules30122655 - 19 Jun 2025

Abstract

N,N-Dimethyl N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetra-hydro-2H-pyran-4-aminium chloride (TAK779) has a potent binding affinity for the chemokine receptor CCR5 and low cytotoxicity; however, their interaction remains unknown. We designed and synthesized four fluorescence-labeled TAK779 analogs as chemical probes. Although the binding properties [...] Read more.

N,N-Dimethyl N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetra-hydro-2H-pyran-4-aminium chloride (TAK779) has a potent binding affinity for the chemokine receptor CCR5 and low cytotoxicity; however, their interaction remains unknown. We designed and synthesized four fluorescence-labeled TAK779 analogs as chemical probes. Although the binding properties of the fluorescence-labeled TAK779 analogs for CCR5 could not be determined, it was found that they penetrate the cell membranes and localize to the microtubes of HeLa cells. Full article

(This article belongs to the Section Bioorganic Chemistry)

► Show Figures

Figure 1

18 pages, 2842 KiB

Open AccessArticle

Optimization of In Vitro Shoot Culture Parameters for Enhanced Biomass and Rosmarinic Acid Production in Salvia atropatana

by Wiktoria Ejsmont, Anna K. Kiss and Izabela Grzegorczyk-Karolak

Molecules 2025, 30(12), 2654; https://doi.org/10.3390/molecules30122654 - 19 Jun 2025

Abstract

Salvia atropatana is a medicinal plant native to Middle Eastern countries. It has been traditionally used in Turkish and Iranian folk medicine to treat infections, wounds, inflammatory diseases, spastic conditions, and diabetes. Its therapeutic potential has been attributed to its essential oil, polyphenolic [...] Read more.

Salvia atropatana is a medicinal plant native to Middle Eastern countries. It has been traditionally used in Turkish and Iranian folk medicine to treat infections, wounds, inflammatory diseases, spastic conditions, and diabetes. Its therapeutic potential has been attributed to its essential oil, polyphenolic acid, flavonoid, and diterpenoid content. The aim of the study was to determine the optimal conditions of in vitro S. atropatana shoot culture to enhance proliferation and secondary metabolite production. It examined the effects of various cytokinins and culture duration on culture growth parameters and phenolic compound accumulation. Exogenous cytokinin supplementation significantly enhanced shoot proliferation, with the highest proliferation ratio (6.3) observed with 1 and 2 mg/L 6-benzylaminopurine (BAP). Biomass accumulation was the highest at 0.5 mg/L BAP, followed by 1 and 2 mg/L meta-toplin (mTOP). Phenolic profiling identified nine compounds, with rosmarinic acid (RA) as the dominant metabolite. The highest RA content (16 mg/g dry weight) was achieved with 1 and 2 mg/L BAP and 0.5 mg/L of its ryboside. The TOPSIS (Technique for Order of Preference by Similarity to Ideal Solution) method identified 1 mg/L BAP as the optimal treatment, balancing high proliferation, biomass, and polyphenol accumulation. Extending culture duration to 50 days increased biomass and phenolic content reaching 19.25 mg/g dry weight. However, morphological changes, including apical necrosis, were observed, and a significantly longer cultivation period was needed, questioning the value of the procedure. This study provides a basis for scalable in vitro production of bioactive compounds in S. atropatana. Full article

(This article belongs to the Special Issue Phytochemical Profiling, Bioactivity, Biotechnology Studies and Practical Applications of Medicinal and Cosmetic Plants)

► Show Figures

Figure 1

27 pages, 2741 KiB

Open AccessArticle

Development and Application of a Senolytic Predictor for Discovery of Novel Senolytic Compounds and Herbs

by Jinjun Li, Kai Zhao, Guotai Yang, Haohao Lv, Renxin Zhang, Shuhan Li, Zhiyuan Chen, Min Xu, Naixue Yang and Shaoxing Dai

Molecules 2025, 30(12), 2653; https://doi.org/10.3390/molecules30122653 - 19 Jun 2025

Abstract

The accumulation of senescent cells is a major contributor to aging and various age-related diseases, making developing senolytic compounds that are capable of clearing these cells an important area of research. However, progress has been hampered by the limited number of known senolytics [...] Read more.

The accumulation of senescent cells is a major contributor to aging and various age-related diseases, making developing senolytic compounds that are capable of clearing these cells an important area of research. However, progress has been hampered by the limited number of known senolytics and the incomplete understanding of their mechanisms. This study presents a powerful senolytic predictor built using phenotypic data and machine learning techniques to identify compounds with potential senolytic activity. A comprehensive training dataset consisting of 111 positive and 3951 negative compounds was curated from the literature. The dataset was used to train machine learning models, incorporating traditional molecular fingerprints, molecular descriptors, and MoLFormer molecular embeddings. By applying MoLFormer-based oversampling and testing different algorithms, it was found that the Support Vector Machine (SVM) and Multilayer Perceptron (MLP) models with MoLFormer embeddings exhibited the best performance, achieving Area Under the Curve (AUC) scores of 0.998 and 0.997, and F1 scores of 0.948 and 0.941, respectively. This senolytic predictor was then used to perform virtual screening of compounds from the DrugBank and TCMbank databases. In the DrugBank database, 98 structurally novel candidate compounds with potential senolytic activity were identified. For TCMbank, 714 potential senolytic compounds were predicted and 81 medicinal herbs with possible senolytic properties were identified. Moreover, pathway enrichment analysis revealed key targets and potential mechanisms underlying senolytic activity. In an experimental screening of predicted compounds, panaxatriol was found to exhibit senolytic activity on the etoposide-induced senescence of the IMR-90 cell line. Additionally, voclosporin was found to extend the lifespan of C. elegans more effectively than metformin, demonstrating the value of our model for drug repurposing. This study not only provides an efficient framework for discovering novel senolytic agents, but also highlights the predicted novel senolytic compounds and herbs as valuable starting points for future research into senolytic drug development. Full article

► Show Figures

Figure 1

19 pages, 20720 KiB

Open AccessArticle

Anti-Anxiety Effects of Essential Oil Microemulsion in Chronic Unpredictable Mild Stress-Induced Rats: Preparation, Characterization, and Mechanisms

by Wenxia Tang, Pan Jiang, Ke Hu, Duo Mei, Qinghao Jiao, Yan Li, Yanping Deng, Jun Wang, Ran Gao, Xin Chen and Jie Yu

Molecules 2025, 30(12), 2652; https://doi.org/10.3390/molecules30122652 - 19 Jun 2025

Abstract

Anxiety disorders, as common neurological diseases in clinical practice, often coexist with depression. Epidemiological surveys indicate that approximately 85% of patients with depression exhibit significant anxiety symptoms. This comorbid state not only exacerbates clinical symptoms but also leads to treatment resistance and prolonged [...] Read more.

Anxiety disorders, as common neurological diseases in clinical practice, often coexist with depression. Epidemiological surveys indicate that approximately 85% of patients with depression exhibit significant anxiety symptoms. This comorbid state not only exacerbates clinical symptoms but also leads to treatment resistance and prolonged disease duration. This study innovatively developed a compound aromatic plant essential oil (EO) formulation with remarkable anxiolytic and antidepressant effects and systematically elucidated its mechanism of action. The study found that the essential oil formulation, administered via inhalation, could significantly improve behavioral abnormalities in animals subjected to the chronic unpredictable mild stress (CUMS) model, specifically manifesting as (1) the reversal of stress-induced weight gain retardation; (2) a significant increase in sucrose preference; (3) an increase in the total distance of spontaneous activity; and (4) the prolongation of exploration time in the open arms of the elevated plus maze. Neuropathological examinations confirmed that the formulation could effectively protect the structural integrity of hippocampal neurons and alleviate CUMS-induced neural damage. In terms of mechanism of action, the study revealed that the formulation regulates the neurotransmitter system through multiple targets: (1) the upregulation of serotonin (5-HT) and γ-aminobutyric acid (GABA) levels; (2) the downregulation of glutamate (GLU) concentration; and (3) key targets identified via network pharmacological analysis, such as ESR1, STAT3, and PPARG. These findings provide molecular-level evidence for understanding the neuromodulatory effects of aromatic essential oils. Pharmaceutical formulation studies showed that the oil-in-water (O/W) type compound essential oil microemulsion, prepared using microemulsification technology, has a uniform particle size and excellent stability, maintaining stable physicochemical properties at room temperature for an extended period, thus laying a foundation for its clinical application. This study not only validates the practical value of traditional medicine but also provides new ideas for the development of novel anxiolytic and antidepressant drugs, achieving an organic integration of traditional experience and modern technology. Full article

(This article belongs to the Section Medicinal Chemistry)

► Show Figures

Figure 1

13 pages, 3268 KiB

Open AccessArticle

Pressure Dependence of Structural Behavior in the Polymorphs of Fe(PM–BiA)₂(NCS)₂

by Pulkit Prakash, Hend Shahed, Ji Qi, Andrzej Grzechnik, Manuel Angst, Jörg Voigt, Jörg Perßon, Yao Cheng, Biliana Gasharova, Yves-Laurent Mathis, Francesco Capitani, Carsten Paulmann, Charlie McMonagle, Dmitry Chernyshov and Karen Friese

Molecules 2025, 30(12), 2651; https://doi.org/10.3390/molecules30122651 - 19 Jun 2025

Abstract

The pressure dependence of structural behavior in the orthorhombic (Pccn, PI) and monoclinic (P2₁/c, PII) polymorphs of the compound [Fe(PM-BiA)₂(NCS)₂], where PM–BiA = (N–(2′–pyridylmethylene)–4-amino–bi–pheynyl), is studied with synchrotron single-crystal X-ray diffraction and [...] Read more.

The pressure dependence of structural behavior in the orthorhombic (Pccn, PI) and monoclinic (P2₁/c, PII) polymorphs of the compound [Fe(PM-BiA)₂(NCS)₂], where PM–BiA = (N–(2′–pyridylmethylene)–4-amino–bi–pheynyl), is studied with synchrotron single-crystal X-ray diffraction and vibrational spectroscopy. Both polymorphs are stable up to ∼1.5 GPa, with a spin state transition occurring only in polymorph PII under hydrostatic conditions as documented by single-crystal synchrotron diffraction. The diffraction data also provide evidence of the formation of superstructures for both PI, with a doubled c axis, and PII, with a doubled b axis, on applying pressures above 2 GPa. The LS and HS states seem to coexist at high-pressures for both polymorphs studied with synchrotron infrared spectroscopy at quasi-hydrostatic conditions. Such results indicate that the occurrence of spin-crossover transformations in [Fe(PM-BiA)₂(NCS)₂] might strongly depend on the stress in the sample. Full article

► Show Figures

Figure 1

21 pages, 1771 KiB

Open AccessArticle

Total Synthesis and Biological Evaluation of 22-Hydroxyacuminatine and the Related Natural Products Norketoyobyrine and Naucleficine

by Shohta Mizuno, Takashi Nishiyama, Hana Bessho, Tetsuya Nakamura, Tomoki Oe, Nanako Hayashi, Yuhzo Hieda, Toshio Motoyashiki, Toshiyuki Hata, Noriyuki Hatae and Tominari Choshi

Molecules 2025, 30(12), 2650; https://doi.org/10.3390/molecules30122650 - 19 Jun 2025

Abstract

Aromathecin compounds—which contain the same indolizine core structure as camptothecin-like compounds—are expected to show anticancer activity. Among them, 22-hydroxyacuminatine—which has a substituent on the E-ring of the pentacyclic scaffold—exhibits topoisomerase 1 inhibitory activity; therefore, the development of efficient methods for its synthesis has [...] Read more.

Aromathecin compounds—which contain the same indolizine core structure as camptothecin-like compounds—are expected to show anticancer activity. Among them, 22-hydroxyacuminatine—which has a substituent on the E-ring of the pentacyclic scaffold—exhibits topoisomerase 1 inhibitory activity; therefore, the development of efficient methods for its synthesis has been actively pursued. Herein, we report a versatile synthetic methodology for introducing various substituents on the E-ring, leading to the total synthesis of 22-hydroxyacuminatine as a model compound of the aromathecin family. The synthesis comprises the following key steps: the synthesis of an isoquinoline N-oxide via the thermal cyclization of 2-alkynylbenzaldehyde oxime, the subsequent Reissert–Henze-type reaction to yield an isoquinolone, and the construction of the indolizine moiety (CD-ring) through C–N bond formation via the Mitsunobu reaction. Consequently, a pentacyclic benz[6,7]indolizino[1,2-b]quinolin-11(13H)-one framework is obtained. Using this methodology, the total synthesis of the natural products norketoyobyrine and naucleficine and an intermediate of the latter, which are indoloquinolizidine-type alkaloids, was achieved, and their antiproliferative activity against HCT-116 human colon cancer cells and HepG2 human liver cancer cells was assessed. Naucleficine and its intermediate exhibited moderate antiproliferative activity against HCT-116 cells, with IC₅₀ values of 55.58 and 41.40 μM, respectively. Full article

(This article belongs to the Special Issue Exclusive Feature Papers in Synthetic Medicinal Chemistry)

► Show Figures

Graphical abstract

18 pages, 1097 KiB

Open AccessArticle

Phytochemical Profiling of Residual Leaves from an Alpine Landrace of Globe Artichoke (Cynara scolymus L.)

by Marco Zuccolo, Angela Bassoli, Annamaria Giorgi, Luca Giupponi, Stefania Mazzini and Gigliola Borgonovo

Molecules 2025, 30(12), 2649; https://doi.org/10.3390/molecules30122649 - 19 Jun 2025

Abstract

The globe artichoke (Cynara cardunculus L. var. scolymus) is a Mediterranean crop valued for its edible capitula and bioactive compounds. Post-harvest residual leaves are among the main by-products of artichoke cultivation and remain largely underutilized. This study reports a comprehensive characterization [...] Read more.

The globe artichoke (Cynara cardunculus L. var. scolymus) is a Mediterranean crop valued for its edible capitula and bioactive compounds. Post-harvest residual leaves are among the main by-products of artichoke cultivation and remain largely underutilized. This study reports a comprehensive characterization of the residual leaves of Carciofo di Malegno, an Alpine artichoke landrace. Comparative analysis was conducted against leaves from two commercial cultivars and a commercial herbal tea product. HPLC analysis revealed that Carciofo di Malegno exhibited the lowest levels of secondary metabolites. Cynaropicrin content was 0.52 ± 0.03 mg/g, lower than in the commercial samples, while the phenolic compounds were below the quantification limit. Proximate analysis indicated a distinctive nutritional profile, with significantly higher ash (8.01 ± 0.04%) and crude fiber (35.75 ± 0.29%) contents compared to all reference samples. These findings highlight the potential of Carciofo di Malegno residual leaves as a sustainable source of nutrients for functional food and nutraceutical applications. Their low content of bitter sesquiterpene lactones may enhance palatability, supporting their valorisation within circular economy frameworks. Moreover, their use may contribute to the in situ conservation of this landrace, reinforcing the link between agrobiodiversity preservation and the sustainable exploitation of agricultural by-products. Full article

(This article belongs to the Section Natural Products Chemistry)

► Show Figures

Figure 1

14 pages, 1417 KiB

Open AccessArticle

Surface and Antimicrobial Properties of Ester-Based Gemini Surfactants

by Iwona Kowalczyk, Adrianna Szulc, Anna Koziróg, Anna Komasa and Bogumił Brycki

Molecules 2025, 30(12), 2648; https://doi.org/10.3390/molecules30122648 - 19 Jun 2025

Abstract

Cationic surfactants, accounting for approximately 7% of the global surfactant market, are widely used in applications such as fabric softeners, biocides, and corrosion inhibitors. Recently, gemini surfactants—comprising two amphiphilic units linked by a spacer—have attracted significant interest due to their superior surface activity, [...] Read more.

Cationic surfactants, accounting for approximately 7% of the global surfactant market, are widely used in applications such as fabric softeners, biocides, and corrosion inhibitors. Recently, gemini surfactants—comprising two amphiphilic units linked by a spacer—have attracted significant interest due to their superior surface activity, lower critical micelle concentrations, and strong antimicrobial properties. However, their poor biodegradability, resulting from their complex molecular structure, has raised environmental concerns. To address this, researchers have developed ester-based gemini surfactants incorporating biodegradable bonds. This study aimed to investigate the relationship between the structure of ester-based gemini surfactants (hydrophobic chain length and spacer type) and their antimicrobial activity against bacteria and fungi. Three series of compounds featuring different functional groups in the spacer were synthesized, along with a trimeric surfactant for comparative purposes. The results demonstrated that both the hydrophobic chain length and the presence of additional cationic groups significantly influence the CMC and antimicrobial performance. Quantum mechanical calculations were also performed to search for correlations between electronic properties and chemical reactivity of compounds. These findings highlight that ester-based gemini surfactants combine high surface and antimicrobial activity with the potential for improved biodegradability, making them promising candidates for use in environmentally friendly applications. Full article

(This article belongs to the Section Organic Chemistry)

► Show Figures

Figure 1

18 pages, 405 KiB

Open AccessArticle

Validated UHPLC Methods for Melatonin Quantification Reveal Regulatory Violations in EU Online Dietary Supplements Commerce

by Celine Vanhee, Cloë Degrève, Niels Boschmans, Yasmina Naïmi, Michael Canfyn, Eric Deconinck and Marie Willocx

Molecules 2025, 30(12), 2647; https://doi.org/10.3390/molecules30122647 - 19 Jun 2025

Abstract

The global sleep aids market has grown significantly due to rising stress and increased awareness of sleep’s importance. Melatonin, available in the EU as a prescription or over-the-counter medicine, depending on the country, is also permitted in dietary supplements with country-specific limits. Recent [...] Read more.

The global sleep aids market has grown significantly due to rising stress and increased awareness of sleep’s importance. Melatonin, available in the EU as a prescription or over-the-counter medicine, depending on the country, is also permitted in dietary supplements with country-specific limits. Recent reports indicate concerning levels of excessive melatonin in EU dietary supplements, necessitating accurate quantification methods. We developed and validated, by applying accuracy profiles, ISO17025-compliant, rapid ultra-high performance liquid chromatography (UHPLC) methodologies coupled with either diode array detection (DAD) or high-resolution accurate mass spectrometry (HRAM MS). The cost-effective UHPLC-DAD method is suitable for medicines and most dietary supplements, except those more complex herbal matrices containing passionflower, hop, hemp, lime tree or lavender or their extracts, where UHPLC-HRAM MS is recommended due to selectivity issues of the DAD methodology. To demonstrate the applicability, we analyzed 50 dietary supplements claiming to contain melatonin—25 from legal supply chains and 25 from suspicious sources claiming therapeutic melatonin content. Our findings confirmed previous reports of high melatonin content in online products, especially when purchased through rogue internet pharmacies. Moreover, 12% of legal supply chain samples violated current legislation through unauthorized health claims or contained at least triple the melatonin amount permitted in Belgium. This research provides reliable analytical methods for regulatory bodies and confirms the circulation of non-compliant melatonin-containing dietary supplements in the EU market, even in the legal supply chain. Full article

(This article belongs to the Special Issue Application of Analytical Methods in Food, Drug, and Natural Products Research: Volume II)

► Show Figures

Figure 1

22 pages, 2341 KiB

Open AccessArticle

Synthesis, Characterization and Biological Profile of Cationic Cobalt Complexes with First-Generation Quinolones

by Alexia Tialiou, Antonios G. Hatzidimitriou and George Psomas

Molecules 2025, 30(12), 2646; https://doi.org/10.3390/molecules30122646 - 19 Jun 2025

Abstract

The interaction of cobalt(II) with first-generation quinolones oxolinic acid (Hoxo), flumequine (Hflmq), pipemidic acid (Hppa) and cinoxacin (Hcx) in the presence of the N,N′-donor heterocyclic ligands 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) afforded a series of novel cobalt complexes, namely [Co(bipy) [...] Read more.

The interaction of cobalt(II) with first-generation quinolones oxolinic acid (Hoxo), flumequine (Hflmq), pipemidic acid (Hppa) and cinoxacin (Hcx) in the presence of the N,N′-donor heterocyclic ligands 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) afforded a series of novel cobalt complexes, namely [Co(bipy)₂(oxo)](PF₆)₂·H₂O (1), [Co(phen)₂(oxo)](PF₆)₂·0.5CH₃OH·0.5H₂O (2), [Co(bipy)₂(flmq)](PF₆)₂·0.5CH₃OH·0.5H₂O (3), [Co(bipy)₂(ppa)](PF₆)₂·CH₃OH·0.5H₂O (4), [Co(phen)₂(cx)](PF₆)₂·CH₃OH·0.5H₂O (5), and [Co(phen)₂(flmq)](PF₆)·0.5CH₃OH·H₂O (6). The characterization of the complexes involved physicochemical techniques, various spectroscopies and single-crystal X-ray crystallography. The affinity of complexes to calf-thymus (CT) DNA was monitored with various techniques, suggesting intercalation in-between the DNA-nucleobases as the most probable interaction mode, which may be combined with electrostatic interactions as a result of the cationic nature of the complexes. The affinity of the complexes for bovine and human serum albumin proteins was monitored, and the determined corresponding albumin-binding constants revealed a tight and reversible interaction. Full article

(This article belongs to the Special Issue Metal-Based Drugs: Past, Present and Future, 3rd Edition)

► Show Figures

Figure 1

Journal Description

Molecules

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI