Molecules

2 pages, 134 KiB

Open AccessCorrection

Correction: Diao et al. Multi-Omics Study on Molecular Mechanisms of Single-Atom Fe-Doped Two-Dimensional Conjugated Phthalocyanine Framework for Photocatalytic Antibacterial Performance. Molecules 2024, 29, 1601

by Shihong Diao, Yixin Duan, Mengying Wang, Yuanjiao Feng, Hong Miao and Yongju Zhao

Molecules 2025, 30(13), 2806; https://doi.org/10.3390/molecules30132806 (registering DOI) - 30 Jun 2025

Abstract

There were citation positioning errors in the original publication [...] Full article

27 pages, 14812 KiB

Open AccessArticle

Computational Kinetic Study on the Intramolecular H-Migration of Hydroperoxyalkylperoxy Radicals (•OOQOOH) in Normal-Alkyl Cyclohexanes

by Xiaoxia Yao, Juanqin Li and Zerong Li

Molecules 2025, 30(13), 2805; https://doi.org/10.3390/molecules30132805 (registering DOI) - 29 Jun 2025

Abstract

Hydroperoxyalkylperoxy radicals (•OOQOOH) are important intermediates in the low-temperature oxidation chemistry of conventional fuels. In these species, a hydrogen atom may migrate from a non-adjacent carbon to the peroxy group, forming a dihydroperoxyalkyl radical (•P(OOH)₂). This research delves into the theoretical [...] Read more.

Hydroperoxyalkylperoxy radicals (•OOQOOH) are important intermediates in the low-temperature oxidation chemistry of conventional fuels. In these species, a hydrogen atom may migrate from a non-adjacent carbon to the peroxy group, forming a dihydroperoxyalkyl radical (•P(OOH)₂). This research delves into the theoretical kinetics of a set of 110 H-migration reactions in normal-alkyl cyclohexanes, calculating high-pressure limit rate constants for these reactions. The reactions are further classified into 15 subclasses based on distinctions in the reaction center and its environment, with rate rules derived by averaging the rate constants within each subclass. A comparison of our calculated rate constants for specific H-migration reactions of •OOQOOH with existing mechanisms and similar reactions in non-cyclic alkanes reveals significant disparities, emphasizing the necessity for precise rate constants tailored to normal-alkyl cyclohexanes. Ethyl cyclohexane mechanisms and n-propyl cyclohexane mechanisms sourced from studies have been improved with high-pressure limit rate constants from this study. Simulations of the low-temperature combustion of ethyl cyclohexane and n-propyl cyclohexane show that the predictions from the updated mechanisms align more closely with the experimental data under specific conditions compared to the original mechanism. Full article

(This article belongs to the Section Physical Chemistry)

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17 pages, 2255 KiB

Open AccessArticle

Engineering a Radiohybrid PSMA Ligand with an Albumin-Binding Moiety and Pharmacokinetic Modulation via an Albumin-Binding Competitor for Radiotheranostics

by Saki Hirata, Hiroaki Echigo, Masayuki Munekane, Kenji Mishiro, Kohshin Washiyama, Takeshi Fuchigami, Hiroshi Wakabayashi, Kazuhiro Takahashi, Seigo Kinuya and Kazuma Ogawa

Molecules 2025, 30(13), 2804; https://doi.org/10.3390/molecules30132804 (registering DOI) - 29 Jun 2025

Abstract

The prostate-specific membrane antigen (PSMA) is a well-established target for radiotheranostics in prostate cancer. We previously demonstrated that 4-(p-astatophenyl)butyric acid (APBA), an albumin-binding moiety (ABM) labeled with astatine-211 (²¹¹At), enables the modulation of pharmacokinetics and enhancement of therapeutic efficacy [...] Read more.

The prostate-specific membrane antigen (PSMA) is a well-established target for radiotheranostics in prostate cancer. We previously demonstrated that 4-(p-astatophenyl)butyric acid (APBA), an albumin-binding moiety (ABM) labeled with astatine-211 (²¹¹At), enables the modulation of pharmacokinetics and enhancement of therapeutic efficacy when combined with the post-administration of an albumin-binding competitor. However, this strategy has not been explored in PSMA-targeting ligands. We designed and synthesized [²¹¹At]6, a novel PSMA ligand structurally analogous to PSMA-617 with APBA. The compound was obtained via a tin–halogen exchange reaction from the corresponding tributylstannyl precursor. Comparative cellular uptake and biodistribution studies were conducted with [²¹¹At]6, its radioiodinated analog [¹²⁵I]5, and [⁶⁷Ga]Ga-PSMA-617. To assess pharmacokinetic modulation, sodium 4-(p-iodophenyl)butanoate (IPBA), an albumin-binding competitor, was administered 1 h postinjection of [¹²⁵I]5 and [²¹¹At]6 at a 10-fold molar excess relative to blood albumin. The synthesis of [²¹¹At]6 gave a radiochemical yield of 15.9 ± 7.7% and a radiochemical purity > 97%. The synthesized [²¹¹At]6 exhibited time-dependent cellular uptake and internalization, with higher uptake levels than [⁶⁷Ga]Ga-PSMA-617. Biodistribution studies of [²¹¹At]6 in normal mice revealed a prolonged blood retention similar to those of [¹²⁵I]5. Notably, post-administration of IPBA significantly reduced blood radioactivity and non-target tissue accumulation of [¹²⁵I]5 and [²¹¹At]6. We found that ABM-mediated pharmacokinetic control was applicable to PSMA-targeted radiotherapeutics, broadening its potential for the optimization of radiotheranostics. Full article

(This article belongs to the Special Issue Advance in Radiochemistry, 2nd Edition)

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16 pages, 4742 KiB

Open AccessArticle

Synthesis, Characterization, and Properties of Novel Coplanar Bicyclic Compounds Based on Triazolofurazane Compounds

by Mei-Qi Xu, Wen-Shuai Dong, Qamar-un-Nisa Tariq, Chao Zhang, Cong Li, Zu-Jia Lu, Bin-Shan Zhao, Qi-Yao Yu and Jian-Guo Zhang

Molecules 2025, 30(13), 2803; https://doi.org/10.3390/molecules30132803 (registering DOI) - 29 Jun 2025

Abstract

In this study, a C-C bond-linked triazole-fused oxadiazole energetic compound, 4-amino-5-(4-amino-1,2,5-oxadiazol-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1), was successfully designed and efficiently synthesized. Following nitration, a functional group-modified nitramine energetic compound (2) was obtained, and its energetic ionic salt (3) [...] Read more.

In this study, a C-C bond-linked triazole-fused oxadiazole energetic compound, 4-amino-5-(4-amino-1,2,5-oxadiazol-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1), was successfully designed and efficiently synthesized. Following nitration, a functional group-modified nitramine energetic compound (2) was obtained, and its energetic ionic salt (3) was further prepared. A comprehensive characterization of the structures of these three compounds was conducted, resulting in the successful elucidation of the single-crystal structures of compound 2·Ca²⁺·6H₂O and compound 3·MeOH. Compound 2 exhibited a positive formation enthalpy (56.2 kJ·mol⁻¹) and moderate mechanical sensitivity (FS = 120 N, IS = 12 J). Due to the presence of the nitramine group, compound 2 exhibited a relatively low thermal decomposition temperature (T_dec = 94 °C). However, the thermal stability of compound 3 was significantly improved (T_dec = 233 °C), which is attributed to salt formation. Compound 3 exhibits a positive formation enthalpy (121.0 kJ·mol⁻¹), along with excellent detonation performance (D = 8120 m·s⁻¹, P = 32.1 GPa) and reduced mechanical sensitivity (FS = 224 N, IS = 24 J). Therefore, the multi-heterocyclic compound, joined via C-C bond linkage, demonstrates outstanding performance, offering a new avenue for the design and synthesis of energetic materials. Full article

(This article belongs to the Section Applied Chemistry)

21 pages, 1179 KiB

Open AccessReview

The Role of Nitric Oxide in Cancer Treatment: Ally or Foe?

by Angelika Myśliwiec, Dorota Bartusik-Aebisher and David Aebisher

Molecules 2025, 30(13), 2802; https://doi.org/10.3390/molecules30132802 (registering DOI) - 29 Jun 2025

Abstract

Nitric oxide (NO), the first gaseous molecule identified as a signaling mediator, plays a pivotal role in numerous physiological processes including cardiovascular regulation, immune response, and neurotransmission. Synthesized from L-arginine by nitric oxide synthase (NOS), NO exerts both protective and cytotoxic effects depending [...] Read more.

Nitric oxide (NO), the first gaseous molecule identified as a signaling mediator, plays a pivotal role in numerous physiological processes including cardiovascular regulation, immune response, and neurotransmission. Synthesized from L-arginine by nitric oxide synthase (NOS), NO exerts both protective and cytotoxic effects depending on its local concentration. At low levels, NO supports tumor growth by mitigating oxidative stress, while at high concentrations, it induces apoptosis through mechanisms such as p53 activation, cytochrome c release, and peroxynitrite formation. These dual properties position NO as a complex but promising agent in cancer therapy. Recent studies have highlighted the potential of NO in enhancing the efficacy of photodynamic therapy (PDT), where it synergizes with reactive oxygen species (ROS) to induce cytotoxic effects in tumor cells. Despite its promise, challenges such as rapid diffusion and limited tumor accumulation hinder NO’s therapeutic utility. This has spurred the development of NO donors and nanotechnology-based delivery systems to enable controlled, site-specific release. Moreover, NO has been shown to counteract multidrug resistance, improve tumor perfusion by dilating vasculature, and potentiate ROS-based therapies like PDT and radiotherapy. However, an emerging concern is NO’s role in promoting proliferation and migration of non-targeted “bystander” tumor cells following PDT-induced stress, primarily through iNOS upregulation. This feedback loop can contribute to tumor aggressiveness and metastasis, underscoring the need for a deeper understanding of NO’s molecular actions. While iNOS inhibitors show preclinical promise in various inflammatory and neoplastic conditions, no such agents have reached clinical approval, due to the complexity and context-dependent effects of NO. Future research should focus on refining NO delivery systems, developing selective iNOS inhibitors, and elucidating NO’s dual role in cancer biology to fully harness its therapeutic potential in PDT and beyond. Full article

(This article belongs to the Special Issue Molecular Approaches to Drug Discovery and Development)

14 pages, 27901 KiB

Open AccessArticle

Inversion Motion of Xanthene and Detection of Its Oxidation Product Xanthone from Gas-Phase Rotational Spectroscopy

by Celina Bermúdez, Manuel Goubet and Elias M. Neeman

Molecules 2025, 30(13), 2801; https://doi.org/10.3390/molecules30132801 (registering DOI) - 29 Jun 2025

Abstract

The rotational spectra of xanthene and its oxidation product xanthone were investigated by combining quantum chemical calculations with Fourier transform microwave spectroscopy in a jet-cooled environment. Xanthone was unexpectedly generated in the experiment when water was present in the reservoir of xanthene leading [...] Read more.

The rotational spectra of xanthene and its oxidation product xanthone were investigated by combining quantum chemical calculations with Fourier transform microwave spectroscopy in a jet-cooled environment. Xanthone was unexpectedly generated in the experiment when water was present in the reservoir of xanthene leading to the total disappearance of xanthene after few hours. Structurally, xanthone shows a near planar disposition, whereas xanthene exhibits a non-planar geometry with both benzene rings twisted out of the molecular plane. This geometry enables an inversion motion between two equivalent conformers, giving rise to a splitting in the ground vibrational state. A two-state analysis of the vibration–rotation interaction for the

v = 0

and

v = 1

states gives an energy separation between these states (inversion splitting) of

Δ E_{01} = 4689.7095 (10) MHz

. This large-amplitude motion leads to vibration–rotation coupling of energy levels. A symmetric double-minimum inversion potential function was determined, resulting in a barrier of about 45 cm

^{- 1}

in good agreement with that obtained by DFT quantum chemical calculations. Full article

(This article belongs to the Special Issue Exclusive Feature Papers in Physical Chemistry, 3nd Edition)

21 pages, 2600 KiB

Open AccessArticle

Comparison of Polyphenolic Content and Bioactivities Between Extracts from the Living Plants and Beach Deposits of the Submerged Brackish Water Angiosperm Ruppia maritima

by Alkistis Kevrekidou, Nikolaos Goutzourelas, Stavroula Savvidi, Varvara Trachana, Andreana N. Assimopoulou, Ming Liu, Paraskevi Malea and Dimitrios Stagos

Molecules 2025, 30(13), 2800; https://doi.org/10.3390/molecules30132800 (registering DOI) - 29 Jun 2025

Abstract

Bioactive extracts from living plants (LR) and beach deposits (NR) of the submerged brackish water angiosperm Ruppia maritima were examined for their antioxidant activity and anticancer potential. LR extract scavenged effectively free radicals with IC₅₀ values of 38.00 μg/mL (DPPH^•), [...] Read more.

Bioactive extracts from living plants (LR) and beach deposits (NR) of the submerged brackish water angiosperm Ruppia maritima were examined for their antioxidant activity and anticancer potential. LR extract scavenged effectively free radicals with IC₅₀ values of 38.00 μg/mL (DPPH^•), 12.00 μg/mL (ABTS^•+), 281.00 μg/mL (OH^•), and 53.00 μg/mL (O₂^•), and exhibited reducing activity with an RP_0.5AU value of 37.00 μg/mL. NR extract retained a significant part of LR extract’s antioxidant activity by scavenging free radicals with IC₅₀ values of 180.00 μg/mL (DPPH^•), 60.00 μg/mL (ABTS^•+), and 164.00 μg/mL (O₂^•), and exhibited reducing activity with an RP_0.5AU value of 107.00 μg/mL. Importantly, NR extract (IC₅₀ value: 60.00 μg/mL) exhibited much higher inhibitory activity than LR extract (IC₅₀ value: 1100.00 μg/mL) in XTT assay. HPLC analysis revealed that both R. maritima extracts contained phenolics, such as chicoric acid, quercetin-3-O-glucopyranoside, p-coumaric acid, 3,5-dimethoxy-4-hydroxicinnanic acid, trans-ferulic acid, and rutin hydrate, possessing antioxidant and/or anticancer activity. Thus, the present study showed for the first time that R. maritima extracts from either LR or NR are a promising source of bioactive compounds having beneficial properties for human health. Full article

(This article belongs to the Special Issue Chemopreventive and Antioxidant Activity of Plant Extracts and Other Phytochemical Compounds)

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17 pages, 1691 KiB

Open AccessArticle

Antimicrobial Activity of Cinnamon, Tea Tree, and Thyme Essential Oils Against Pathogenic Bacteria Isolated from Tilapia (Oreochromis spp.) in Aquaculture Farms

by Karen A. Terrazas-Pineda, Liliana Alamilla-Beltrán, Claudia Ariadna Acero-Ortega, Juan Antonio Damas-Espinoza, Georgina Calderón-Domínguez, Rosalva Mora-Escobedo, Vicente Vega-Sánchez and Fabián Ricardo Gómez-de Anda

Molecules 2025, 30(13), 2799; https://doi.org/10.3390/molecules30132799 (registering DOI) - 28 Jun 2025

Abstract

Overexploitation has led to a rise in pathogenic bacteria within aquaculture, increasing reliance on antibiotics, and developing microorganism resistance. This situation underscores the need to explore alternatives with a reduced ecological impact. Metabolites derived from essential oils have demonstrated antimicrobial properties that can [...] Read more.

Overexploitation has led to a rise in pathogenic bacteria within aquaculture, increasing reliance on antibiotics, and developing microorganism resistance. This situation underscores the need to explore alternatives with a reduced ecological impact. Metabolites derived from essential oils have demonstrated antimicrobial properties that can inhibit or diminish the activity of various microorganisms. In this study, the antimicrobial efficacy of cinnamon (Cinnamomum zeylanicum), tea tree (Melaleuca alternifolia), and thyme (Thymus vulgaris) essential oils against pathogenic bacteria (Aeromonas, Pseudomonas, Shewanella, Comamonas, Vibrio, Acinetobacter, and Empedobacter) isolated from tilapia (Oreochromis spp.) brooded in Hidalgo State, Mexico, were investigated. Diffusion tests were conducted using discs infused with 12 different antibiotics and discs infused with essential oils at concentrations of 15, 10, and 5 μL each. Minimal inhibitory concentration tests were performed using a 96-well microplate format. All bacterial strains exhibited multi-resistance to various antibiotics; however, thyme and cinnamon effectively inhibited the tested bacteria at the lowest concentrations, while tea tree oil was the least effective. The findings suggest the potential incorporation of thyme and cinnamon as an alternative prevention to decrease the use of antibiotic treatment. Full article

(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)

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13 pages, 2471 KiB

Open AccessArticle

Portable and Rapid Smartphone-Based Colorimetric Assay of Peracetic Acid for Point-of-Use Medical/Pharmaceutical Disinfectant Preparation

by Suphakorn Katib, Sutasinee Apichai, Jutamas Jiaranaikulwanitch, Busaban Sirithunyalug, Fumihiko Ogata, Naohito Kawasaki, Kate Grudpan and Chalermpong Saenjum

Molecules 2025, 30(13), 2798; https://doi.org/10.3390/molecules30132798 (registering DOI) - 28 Jun 2025

Abstract

A simple and rapid smartphone-based colorimetric assay for peracetic acid concentration was developed to facilitate point-of-use disinfectant preparations for infection prevention and control. The colorimetric detection was based on the oxidation of N,N-diethyl-phenylenediamine by peracetic acid through an intermediate reaction with potassium iodide, [...] Read more.

A simple and rapid smartphone-based colorimetric assay for peracetic acid concentration was developed to facilitate point-of-use disinfectant preparations for infection prevention and control. The colorimetric detection was based on the oxidation of N,N-diethyl-phenylenediamine by peracetic acid through an intermediate reaction with potassium iodide, resulting in pink-magenta products. The colorimetric reaction was performed on a 96-well plate; then, the color products were photographed in one image. The color intensity was evaluated to determine the peracetic acid concentration using a custom-built mobile application named Modern Peracetic Acid Analysis. The relative green intensity of the pink-magenta products was directly proportional to the peracetic acid concentration in the range of 0.15 to 3.0 µg/mL. The detection and quantitation limits were 0.11 µg/mL and 0.34 µg/mL, respectively. The approach was successfully applied to determine the peracetic acid concentration in pharmaceutical disinfectant formulations. The results obtained using the proposed approach showed no significant differences from those obtained using acid–base titration at the 95% confidence level. The greenness of the proposed approach was evaluated using the Complementary Green Analytical Procedure Index, Analytical Greenness, and Blue Applicability Grade Index, demonstrating enhanced environmental friendliness and practical advantages, as well as simple, portable instrumentation that is easier to operate than traditional spectrophotometric and titration methods. Furthermore, a sustainability assessment based on the Need, Quality, and Sustainability index underscored its enhanced sustainability. Full article

(This article belongs to the Special Issue Advances in Green Analytical Chemistry)

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11 pages, 2272 KiB

Open AccessCommunication

Synthesis of Conjugated Tris- and Tetrakis (Carbazolyl) Azulenes with Intense Emission in the Visible Range

by Amantay Iskanderov, Nurlan Merkhatuly, Ablaykhan Iskanderov, Saltanat Abeuova and Pavel Vojtisek

Molecules 2025, 30(13), 2797; https://doi.org/10.3390/molecules30132797 (registering DOI) - 28 Jun 2025

Abstract

New conjugated carbazolyl-substituted azulenes, such as 1,2,3-tris(carbazolyl)azulene and 1,2,3,6-tetrakis(carbazolyl)azulene, were synthesized via cross-coupling reactions in high yields. The resulting compounds exhibit a significant ability to absorb and emit light in the visible region, in the range of 400 to 600 nanometers. Studies have [...] Read more.

New conjugated carbazolyl-substituted azulenes, such as 1,2,3-tris(carbazolyl)azulene and 1,2,3,6-tetrakis(carbazolyl)azulene, were synthesized via cross-coupling reactions in high yields. The resulting compounds exhibit a significant ability to absorb and emit light in the visible region, in the range of 400 to 600 nanometers. Studies have shown that azulene with carbazolyl substituents at positions 1, 2, 3, and 6 possesses unique photophysical properties, manifested as intense emission in the blue photoluminescence region (λ_PL at 444 and 490 nm), which is not observed in the original azulene. This feature arises due to the donor properties of carbazolyl substituents, which have a strong effect on the electronic structure of azulene, creating the conditions for a permitted HOMO-LUMO electronic transition. Full article

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12 pages, 1777 KiB

Open AccessArticle

Development of Melt-Castable Explosive: Targeted Synthesis of 3,5-Dinitro-4-Methylnitramino-1-Methylpyrazole and Functional Derivatization of Key Intermediates

by Elena Reinhardt, Lukas Bauer, Antonia H. Stadler, Henrik R. Wilke, Arthur Delage, Jörg Stierstorfer and Thomas M. Klapötke

Molecules 2025, 30(13), 2796; https://doi.org/10.3390/molecules30132796 (registering DOI) - 28 Jun 2025

Abstract

The problems associated with TNT necessitate the development of novel melt-castable compounds with melting points between 70 and 120 °C, a crucial endeavor in the field of energetic materials. This study introduces a promising melt-castable explosive based on nitropyrazole, whose melt-castable properties were [...] Read more.

The problems associated with TNT necessitate the development of novel melt-castable compounds with melting points between 70 and 120 °C, a crucial endeavor in the field of energetic materials. This study introduces a promising melt-castable explosive based on nitropyrazole, whose melt-castable properties were achieved by the introduction of methyl groups. The synthesis of 3,5-dinitro-4-methylnitramino-1-methylpyrazole involves a three-step process starting from 3,5-dinitro-4-chloropyrazole, including substitution, nitration, and methylation reactions. Additionally, two alternative synthesis routes and six energetic salts were examined. Structural elucidation was conducted using conventional methods such as NMR, IR, and X-ray, while the energetic properties of the compound, including thermal behavior, sensitivities, and theoretical performance, were investigated. Also, compatibility with common explosives was investigated, the experimental enthalpy of formation by bomb calorimetry was determined, and an SSRT test was performed. Furthermore, the melt-cast explosive underwent an Ames test in order to assess its toxicity. Full article

(This article belongs to the Special Issue Molecular Design and Synthesis of Novel Energetic Compounds)

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20 pages, 698 KiB

Open AccessReview

Mechanisms of Action of Propofol in Modulating Microglial Activation in Ischemic Stroke

by Pouria Abdolmohammadi, Bashir Bietar, Juan Zhou and Christian Lehmann

Molecules 2025, 30(13), 2795; https://doi.org/10.3390/molecules30132795 (registering DOI) - 28 Jun 2025

Abstract

Ischemic stroke, responsible for the majority of stroke cases worldwide, triggers profound neuroinflammatory responses largely mediated by microglia. Excessive activation of pro-inflammatory microglia exacerbates neuronal injury, highlighting the need for therapeutic strategies targeting microglial modulation. Propofol (2,6-diisopropylphenol), a widely used intravenous anesthetic, has [...] Read more.

Ischemic stroke, responsible for the majority of stroke cases worldwide, triggers profound neuroinflammatory responses largely mediated by microglia. Excessive activation of pro-inflammatory microglia exacerbates neuronal injury, highlighting the need for therapeutic strategies targeting microglial modulation. Propofol (2,6-diisopropylphenol), a widely used intravenous anesthetic, has emerged as a promising neuroprotective agent due to its potent anti-inflammatory properties. This review comprehensively explores the diverse cellular mechanisms by which propofol attenuates microglial activation and inflammation in ischemic stroke. By elucidating these molecular pathways, it underscores the therapeutic potential of propofol in mitigating ischemic brain injury and guiding future clinical interventions. Full article

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15 pages, 5168 KiB

Open AccessArticle

The Anisotropic Electrothermal Behavior and Deicing Performance of a Self-Healing Epoxy Composite Reinforced with Glass/Carbon Hybrid Fabrics

by Ting Chen and Xusheng Du

Molecules 2025, 30(13), 2794; https://doi.org/10.3390/molecules30132794 (registering DOI) - 28 Jun 2025

Abstract

Hybrid fiber-reinforced polymer-laminated composites are often used under icy conditions (such as for reinforcing parts in aircraft frames and bridge beams), where there is an urgent demand for deicing. In this paper, besides the different mechanical properties of laminates along the longitudinal carbon [...] Read more.

Hybrid fiber-reinforced polymer-laminated composites are often used under icy conditions (such as for reinforcing parts in aircraft frames and bridge beams), where there is an urgent demand for deicing. In this paper, besides the different mechanical properties of laminates along the longitudinal carbon fiber (CF) and glass fiber (GF) directions, the anisotropic electrothermal behavior of a hybrid glass/carbon fiber-reinforced epoxy (GCF/EP) is also investigated, as well as its deicing performance and self-repairing capability. The surface equilibrium temperature of GCF/EP composites can conveniently be adjusted by tuning the current magnitude and its flow direction. Compared to the longitudinal CF direction of the GCF/EP, where 0.3 A was loaded to achieve a surface equilibrium temperature of 122.8 °C, a much weaker current (0.03 A) was needed to load along the longitudinal GF direction to reach almost the same temperature. However, besides the higher flexural strength and fast temperature response, along the longitudinal CF direction, the GCF/EP exhibited excellent deicing performance, including a shorter time and larger energy efficiency. Furthermore, the self-repairing ability of the GCF/EP and its effect on the deicing performance of the composite were characterized. Studying the Joule heating effect of GCF/EP composite laminates and their corresponding deicing performance lays the foundation for their design and practical application in icy environments. Full article

(This article belongs to the Special Issue Micro/Nano-Materials for Anti-Icing and/or De-Icing Applications)

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16 pages, 7039 KiB

Open AccessArticle

A Novel HDAC6 Inhibitor Enhances the Efficacy of Paclitaxel Against Ovarian Cancer Cells

by An-Jui Chi, Jui-Ling Hsu, Yun-Xin Xiao, Ji-Wang Chern, Jih-Hwa Guh, Chao-Wu Yu and Lih-Ching Hsu

Molecules 2025, 30(13), 2793; https://doi.org/10.3390/molecules30132793 (registering DOI) - 28 Jun 2025

Abstract

Ovarian cancer cells overexpress HDAC6, and selective HDAC6 inhibitors have been considered potential new drugs for ovarian cancer either alone or in combination with other anticancer agents. We screened 46 potential novel HDAC6 inhibitors in ES-2 ovarian cancer cells and showed that compound [...] Read more.

Ovarian cancer cells overexpress HDAC6, and selective HDAC6 inhibitors have been considered potential new drugs for ovarian cancer either alone or in combination with other anticancer agents. We screened 46 potential novel HDAC6 inhibitors in ES-2 ovarian cancer cells and showed that compound 25253 demonstrated the most potent anti-proliferative activity and effective synergy with paclitaxel, which was also validated in TOV21G ovarian cancer cells. The combination of 25253 and paclitaxel significantly induced subG1 and apoptotic cells, revealed by PI staining assay and Annexin V-FITC/PI double staining assay, respectively. Western blot analysis showed downregulation of Bcl-2 and Bcl-XL, and upregulation of Bax and Bak, indicating that apoptosis was mediated through the intrinsic pathway. The combination increased γ-H2AX and p-p53 protein levels, suggesting the induction of DNA damage. Furthermore, HDAC6 was downregulated and acetylated α-tubulin was profoundly increased. Compound 25253 enhanced the inhibitory effect of paclitaxel on cell migration and invasion, possibly due to the extensive accumulation of acetylated α-tubulin, which affected microtubule dynamics. Taken together, the combination of 25253 and paclitaxel synergistically inhibited the growth, migration, and invasion of ovarian cancer cells and induced apoptosis, providing supporting evidence that the combination of HDAC6 inhibitors and paclitaxel may be a promising treatment strategy for ovarian cancer. Full article

(This article belongs to the Special Issue Innovative Anticancer Compounds and Therapeutic Strategies)

30 pages, 2265 KiB

Open AccessReview

Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview

by Wang Wang, Hanting Zhou, Akanksha Sen, Pengxia Zhang, Linhong Yuan and Shaobo Zhou

Molecules 2025, 30(13), 2792; https://doi.org/10.3390/molecules30132792 (registering DOI) - 28 Jun 2025

Abstract

Astragalus polysaccharides (APS), bioactive compounds derived from Astragalus membranaceus, have emerged as promising natural agents in the treatment of hepatocellular carcinoma, a leading cause of cancer-related mortality. Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including [...] Read more.

Astragalus polysaccharides (APS), bioactive compounds derived from Astragalus membranaceus, have emerged as promising natural agents in the treatment of hepatocellular carcinoma, a leading cause of cancer-related mortality. Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of autophagy, and modulation of immune responses. These therapeutic effects are closely associated with the regulation of critical signalling pathways, such as PI3K/AKT/mTOR, Wnt/β-catenin, JAK/STAT, and TGF-β/Smad. APS also reshapes the tumour microenvironment by enhancing macrophage activity, reducing the regulatory T cell function, and improving host immune response. In addition, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity. Despite the robust experimental evidence, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation. This review summarises the recent advances in understanding the anti-hepatocellular carcinoma activities of APS, their molecular targets and potential applications, aiming to provide a scientific basis for future studies and the development of APS-based therapeutic strategies. Full article

(This article belongs to the Special Issue Effects of Functional Foods and Dietary Bioactives on Human Health)

18 pages, 3571 KiB

Open AccessArticle

Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-b]Quinazolin-9(1H)-ones as Cholinesterase Inhibitors Targeting Alzheimer’s Disease Through Suzuki–Miyaura Cross-Coupling Reaction

by Davron Turgunov, Lifei Nie, Azizbek Nasrullaev, Zarifa Murtazaeva, Bianlin Wang, Dilafruz Kholmurodova, Rustamkhon Kuryazov, Jiangyu Zhao, Khurshed Bozorov and Haji Akber Aisa

Molecules 2025, 30(13), 2791; https://doi.org/10.3390/molecules30132791 (registering DOI) - 28 Jun 2025

Abstract

An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one. The derivatives were created [...] Read more.

An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer’s disease. The conditions for the Suzuki–Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman’s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one derivative exhibited the highest inhibitory potency, with an IC₅₀ value of 6.084 ± 0.26 μM. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer’s disease. Full article

(This article belongs to the Special Issue Synthesis and Derivatization of Heterocyclic Compounds)

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25 pages, 10381 KiB

Open AccessArticle

Molecular Insights into the Interaction of Orexin 1 Receptor Antagonists: A Comprehensive Study Using Classical and Quantum Computational Methods

by Caio Sena, Pedro Albuquerque, Jonas Oliveira and Davi Vieira

Molecules 2025, 30(13), 2790; https://doi.org/10.3390/molecules30132790 (registering DOI) - 28 Jun 2025

Abstract

Sleep disorders, such as insomnia and narcolepsy, significantly impact quality of life. They are often associated with long-term health consequences, including cardiovascular disease, immune dysfunction, and cognitive impairment. While traditional treatments, such as sedatives and hypnotics, can be effective, they are limited by [...] Read more.

Sleep disorders, such as insomnia and narcolepsy, significantly impact quality of life. They are often associated with long-term health consequences, including cardiovascular disease, immune dysfunction, and cognitive impairment. While traditional treatments, such as sedatives and hypnotics, can be effective, they are limited by issues of tolerance and dependence. The orexinergic system, particularly the orexin 1 receptor (OXR1), has emerged as a promising therapeutic target due to its central role in regulating sleep–wake cycles. In this study, we investigate the molecular interactions of three OXR1 antagonists—daridorexant, lemborexant, and suvorexant—using an integrated computational approach combining molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and the molecular fractionation with conjugate caps (MFCC) methodology. The MFCC approach enabled the precise quantification of interaction energies between ligands and key receptor residues, providing detailed insights into the contributions of specific amino acids to binding stability. Our results reveal that residues such as GLU204, HIS216, and ASN318 play critical roles in stabilizing ligand–receptor interactions, with a marked decrease in binding energy magnitude as dielectric constants increase. Daridorexant exhibited the strongest interaction energy, driven by hydrogen bonds and hydrophobic contacts, while lemborexant and suvorexant showed distinct stabilization patterns mediated by hydrophobic interactions. These findings provide a robust molecular basis for the rational design of next-generation OXR1 antagonists with improved efficacy and safety profiles. By elucidating drug–receptor interactions at the atomic level, this research underscores the impact of integrated computational approaches in drug discovery. It supports the development of precise targeted therapies for sleep disorders. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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16 pages, 2069 KiB

Open AccessArticle

Natural-Origin Edible Gels as Delivery Systems for Green Tea Extract: Formulation, Physicochemical, and Biopharmaceutic Profile Assessment

by Andreja Poceviciute, Agne Mazurkeviciute and Lina Raudone

Molecules 2025, 30(13), 2789; https://doi.org/10.3390/molecules30132789 (registering DOI) - 28 Jun 2025

Abstract

Natural-origin edible gels are gaining attention as innovative carriers for bioactive compounds, offering consumer-friendly formats and potential to enhance stability and bioavailability. This study aimed to develop and characterize edible gels incorporating Camellia sinensis (L.) Kuntze extract using different plant-based gelling agents, including [...] Read more.

Natural-origin edible gels are gaining attention as innovative carriers for bioactive compounds, offering consumer-friendly formats and potential to enhance stability and bioavailability. This study aimed to develop and characterize edible gels incorporating Camellia sinensis (L.) Kuntze extract using different plant-based gelling agents, including whole flaxseeds, ground flaxseeds, medium-size oatmeal, and coarse oatmeal. The physical properties of the gels were evaluated by rheological (flow curve) and pH studies. The phytochemical composition of the green tea extract and gels with this extract and the main phenolic compounds, including catechins, gallic acid, and caffeine, were evaluated by high-performance liquid chromatography. The biopharmaceutical properties of the prepared gels were evaluated by dissolution testing. Rheological analysis revealed that oat-based gels exhibited higher viscosity (up to 24.33 Pa·s) compared to flaxseed-based gels. Despite differences in consistency, no statistically significant differences were found in total phenolic release among gel formulations (p > 0.05), except for epigallocatechin, which showed significantly higher release from coarse oatmeal gels (p > 0.05). The findings suggest that both flaxseed- and oatmeal-based gels are promising natural carriers for green tea phytochemicals, offering standardized dosing and potential cognitive health benefits. Further studies are warranted to assess the in vivo bioavailability and long-term stability of these formulations. Full article

(This article belongs to the Special Issue Extraction, Characterization, and Potential Applications of Bioactive Molecules from Natural Sources, 4th Edition)

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17 pages, 5903 KiB

Open AccessArticle

New Cation Sensors Based on Eugenol-Derived Azo Dyes

by José R. A. Coelho, Ana Rita F. Pacheco, Diogo C. Domingues, Ana Rita O. Rodrigues, Akani A. Temitope, Paulo J. G. Coutinho, Maria José G. Fernandes, Elisabete M. S. Castanheira and M. Sameiro T. Gonçalves

Molecules 2025, 30(13), 2788; https://doi.org/10.3390/molecules30132788 (registering DOI) - 28 Jun 2025

Abstract

Eugenol-based azo dyes illustrate how bio-sourced compounds like eugenol can be transformed through synthetic processes into functional and colorful compounds. The main purpose of the present work was to develop new responsive colorimetric sensors for metal cations based on eugenol-derived azo compounds. The [...] Read more.

Eugenol-based azo dyes illustrate how bio-sourced compounds like eugenol can be transformed through synthetic processes into functional and colorful compounds. The main purpose of the present work was to develop new responsive colorimetric sensors for metal cations based on eugenol-derived azo compounds. The incorporation of the azo group into the eugenol framework allows for strong electronic interactions with metal cations, leading to distinct color changes observable to the naked eye. These azo-eugenol dyes exhibit shifts in their UV-Vis absorption spectra upon complexation with metal cations such as copper (Cu²⁺) and lead (Pb²⁺), making them effective sensors for environmental and analytical applications. The eugenol-based azo dyes were subjected to photophysical studies to understand selectivity, response time, and stability in relation to metal cations, which will be a starting point for the monitoring of toxic metal contaminants in aqueous environments. Full article

(This article belongs to the Section Analytical Chemistry)

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