Molecules

29 pages, 21572 KB

Open AccessArticle

Combinatorial Treatment with Chlorogenic Acid and Cinnamaldehyde Disrupts Intracellular pH and Metabolic Transport in Breast Cancer Cells

by Yusuff Olayiwola, Vindya Edgunpati, Li Li and Lauren Gollahon

Molecules 2026, 31(16), 2939; https://doi.org/10.3390/molecules31162939 - 21 Aug 2026

Viewed by 401

Abstract

Breast cancer cells exhibit a reversed pH gradient and metabolic plasticity that promote proliferation, invasion, and resistance to therapy. Natural products such as chlorogenic acid (CGA) and cinnamaldehyde (CA) have shown emerging anticancer potential. However, their effects on intracellular pH and metabolic transport [...] Read more.

Breast cancer cells exhibit a reversed pH gradient and metabolic plasticity that promote proliferation, invasion, and resistance to therapy. Natural products such as chlorogenic acid (CGA) and cinnamaldehyde (CA) have shown emerging anticancer potential. However, their effects on intracellular pH and metabolic transport systems remain undefined. Therefore, the aim of this study was to characterize these parameters in breast cancer and non-tumorigenic breast cells. This study evaluated the physiochemical properties of CGA and CA using LC–MS, under pH conditions (pH 1.2, 7.4, and 9.0) mimicking the gastrointestinal track (GIT). Additionally, LC–MS-based human liver microsome (HLM) assays with NADPH were used to evaluate susceptibility to CYP-mediated metabolism to evaluate first-pass metabolic stability. Intracellular uptake kinetics were quantified at multiple time points using LC–MS. Following CGA:CA treatment, intracellular pH (pH_i) was measured in cancerous MDA-MB-231 and non-tumorigenic MCF-10A breast cell lines using SNARF-1 targeted ratio-metric fluorescence approach. Expression of OATP1B1, GLUT1, and MCT1 were analyzed by Western and immunofluorescence respectively, to assess potential cellular uptake of CGA:CA through OATP1B1 and their effects on glucose uptake and lactate and proton transport. Physiochemical results demonstrated that the compounds ranged from fully stable (pH 1.2 and 7.4) to completely unstable (pH 9.0). HLM incubation indicated no CYP-mediated hepatic metabolism. Treatment results showed that there was rapid intracellular uptake of CGA and CA in cancer cells and that CGA:CA lowered pH_i in both MDA-MB-231 and MCF-7 cells, while pH_i remained mostly unchanged in MCF-10A cells. Protein analysis revealed that CGA:CA treatment downregulated GLUT1 and MCT1 expression in cancer cells, suggesting impaired glycolytic activity and lactate shuttling. OATP1B1 expression was significantly suppressed in cancer cells, suggesting feedback inhibition of the solute carrier protein. Collectively, these findings indicate that CGA and CA exhibit favorable biochemical stability and disrupt intracellular pH regulation and metabolic transporter expression in breast cancer cells. Importantly, normal cells are not significantly affected. Thus, CGA:CA demonstrates therapeutic potential for breast cancer through pH_i and metabolic modulation. Full article

(This article belongs to the Special Issue Recent Advances in Development of Small Molecules to Fight Cancer—3rd Edition)

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30 pages, 4016 KB

Open AccessReview

Multi-Platform Metabolomics for Fraud Detection in Spices and Botanical Food Supplements: From Fingerprint Acquisition to Decision-Grade Evidence

by Dejan Gođevac, Stefan Ivanović, Mirjana Cvetković, Jovana Stanković Jeremić, Katarina Simić, Manuela Mandrone and Ivana Sofrenić

Molecules 2026, 31(16), 2938; https://doi.org/10.3390/molecules31162938 - 21 Aug 2026

Viewed by 388

Abstract

Fraud in herbal medicines and botanical supplements—such as biological substitution, dilution with inert material, undeclared active pharmaceutical ingredients (APIs), and intentional mislabeling—represents a significant and underestimated threat to public health. Beyond regulatory problems, fraudulent botanical products also compromise the scientific integrity of bioactive [...] Read more.

Fraud in herbal medicines and botanical supplements—such as biological substitution, dilution with inert material, undeclared active pharmaceutical ingredients (APIs), and intentional mislabeling—represents a significant and underestimated threat to public health. Beyond regulatory problems, fraudulent botanical products also compromise the scientific integrity of bioactive compound research. If pharmacological or clinical studies are carried out on adulterated material without knowing it, the resulting data on safety and efficacy become unreliable, and any conclusions drawn from such data are questionable. This review critically evaluates multi-platform metabolomics as an analytical decision-making framework for botanical fraud detection. Rather than cataloging available methods, we focus on the complete analytical pipeline: study design and sample strategy, multi-platform fingerprint acquisition and processing (NMR, GC-MS, LC-HRMS, HPTLC), and chemometric modeling, validation, and decision support. Particular emphasis is placed on data fusion across platforms and the requirements for producing decision-grade evidence—analytical outputs robust enough to support market monitoring and regulatory action. Full article

(This article belongs to the Special Issue Natural and Synthetic Bioactive Compounds in Food—Risks and Benefits)

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14 pages, 872 KB

Open AccessArticle

Fluid-Improved Particle Swarm Optimization for Parameter Optimization of XRD-Based Os Draconis Identification Model

by Yuchen Wang, Hongyan Zhai, Jimin Deng, Lu Cheng, Ye Tao, Jinfeng Chen, Min Tang, Kang Wang and Yazhong Zhang

Molecules 2026, 31(16), 2937; https://doi.org/10.3390/molecules31162937 - 21 Aug 2026

Viewed by 263

Abstract

During the X-ray Diffraction (XRD) identification of the traditional Chinese medicine Os Draconis, the identification model often suffers from limited classification accuracy due to the difficulty in determining optimal parameters. To address this issue, this paper proposes a Hydrodynamic Improved Particle Swarm [...] Read more.

During the X-ray Diffraction (XRD) identification of the traditional Chinese medicine Os Draconis, the identification model often suffers from limited classification accuracy due to the difficulty in determining optimal parameters. To address this issue, this paper proposes a Hydrodynamic Improved Particle Swarm Optimization (HIIPSO) algorithm for the deep optimization of model parameters. In practical identification scenarios, the high complexity of XRD data poses severe challenges to the convergence speed and global search capability of optimization algorithms. To enhance model performance, this study introduces the interaction mechanism from fluid dynamics into the particle swarm optimization process. Specifically, HIIPSO incorporates a Voronoi neighbor topology to enhance population diversity and spatial distribution rationality. Concurrently, a hydrodynamic interaction mechanism is constructed to simulate the cooperative behavior of particles in a fluid environment, thereby effectively preventing the algorithm from falling into local optima. A theoretical analysis of the computational complexity of the HIIPSO algorithm in the parameter search task for XRD identification models was conducted, confirming that it falls within an ideal range for engineering applications. Statistical analysis of the experimental results demonstrates that, in the parameter optimization task for the Os Draconis identification model, the HIIPSO algorithm significantly outperforms traditional and other baseline algorithms across key metrics, including the optimal value, mean, standard deviation, and median of the objective function. The experimental data indicates that the HIIPSO algorithm can substantially improve the robustness and identification accuracy of the XRD-based Os Draconis identification model, making it an optimal solution for parameter optimization problems in the digital identification of complex mineral-based traditional Chinese medicines. Full article

(This article belongs to the Special Issue Identification, Isolation, and Analysis of Phytochemicals from Plant-Derived Products)

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21 pages, 13488 KB

Open AccessArticle

Amphiphilic Covalent Organic Framework for Efficient DHT Adsorption and Androgenetic Alopecia Treatment via Spectral Technology

by Jiahui Wei, Fanqiang Bu, Bing Zhao, Qi Liu and Jinqiang Wu

Molecules 2026, 31(16), 2936; https://doi.org/10.3390/molecules31162936 - 21 Aug 2026

Viewed by 334

Abstract

Androgenetic alopecia (AGA) is a prevalent clinical disorder, and the key pathogenic factor is dihydrotestosterone (DHT) present in the pilosebaceous unit. Current clinical therapeutic options are often associated with notable adverse effects, highlighting the urgent need for safer and more effective interventions. Herein, [...] Read more.

Androgenetic alopecia (AGA) is a prevalent clinical disorder, and the key pathogenic factor is dihydrotestosterone (DHT) present in the pilosebaceous unit. Current clinical therapeutic options are often associated with notable adverse effects, highlighting the urgent need for safer and more effective interventions. Herein, a novel amphiphilic covalent organic framework (amCOF) is designed and synthesized. By simultaneously incorporating hydrophilic functional groups and lipophilic alkyl chains into the covalent organic skeleton, the material exhibits excellent amphiphilicity, high specific surface area, and well-ordered porous structures. Owing to its amphiphilic nature, amCOF disperses uniformly in aqueous physiological media and adapts favorably to the lipophilic microenvironment within hair follicles. Furthermore, the ordered porous architecture endows amCOF with rapid DHT adsorption kinetics, high adsorption capacity, and high removal efficiency. Functional assays demonstrate that amCOF effectively reverses the inhibitory effects of DHT on the proliferation and migration of human dermal papilla cells. In animal models, topical application of amCOF significantly reduces local DHT concentrations, promotes hair regrowth, and shows favorable biosafety profiles. Collectively, this work provides a new strategy for treating androgenetic alopecia by scavenging pathogenic lipophilic molecules from sebum using amphiphilic porous materials and also establishes a solid foundation for expanding the biomedical applications of COFs. Full article

(This article belongs to the Special Issue Spectrophotometric Applications in Chemistry)

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45 pages, 44829 KB

Open AccessReview

Progress in DFT Studies of BiOF: Crystals, Defects, Doping and Heterojunctions

by Shuili Zhang, Chao Wang, Xiong Zhang and Pengju Li

Molecules 2026, 31(16), 2935; https://doi.org/10.3390/molecules31162935 - 21 Aug 2026

Viewed by 266

Abstract

BiOF has emerged as a promising functional material for photocatalysis, electrochemical energy storage, and ion adsorption due to its unique layered structure, excellent chemical stability, and tunable electronic properties. Density functional theory (DFT) calculations provide in-depth theoretical insights into the crystal structure, intrinsic [...] Read more.

BiOF has emerged as a promising functional material for photocatalysis, electrochemical energy storage, and ion adsorption due to its unique layered structure, excellent chemical stability, and tunable electronic properties. Density functional theory (DFT) calculations provide in-depth theoretical insights into the crystal structure, intrinsic defects, doping modification, and heterostructure construction of BiOF. This review systematically summarizes the recent DFT research progress of BiOF systems. Computational results reveal the lattice characteristics, bandgap features, built-in electric field distribution and facet anisotropy of BiOF, and highlight the critical influence of Bi semicore states on structural relaxation and electronic modulation. Defect engineering of bismuth and oxygen vacancies can effectively optimize band structure, accelerate carrier separation and improve catalytic performance. Cation and anion doping introduce impurity energy levels to narrow the bandgap and broaden the visible-light response range. Various BiOF-based heterostructures with different band alignment modes are analyzed, and the interfacial built-in electric field dominates charge separation, while excessive formation energy and unfavorable charge transfer still restrict material optimization. This work provides a systematic theoretical reference for the rational design and performance improvement of high-efficiency BiOF-based materials. Full article

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22 pages, 2213 KB

Open AccessReview

Compositional Diversity and Functional Interactions of Bioactive Compounds in Japanese Green Tea: Focus on Matcha, Sencha, and Gyokuro

by Keiko Unno, Yoko Kameoka and Yoriyuki Nakamura

Molecules 2026, 31(16), 2934; https://doi.org/10.3390/molecules31162934 - 21 Aug 2026

Viewed by 472

Abstract

Japanese green teas, including matcha, sencha, and gyokuro, are derived from the leaves of Camellia sinensis and contain bioactive compounds such as catechins, caffeine, and amino acids, notably theanine. However, the amounts and ratios of these components vary significantly depending on the harvest [...] Read more.

Japanese green teas, including matcha, sencha, and gyokuro, are derived from the leaves of Camellia sinensis and contain bioactive compounds such as catechins, caffeine, and amino acids, notably theanine. However, the amounts and ratios of these components vary significantly depending on the harvest season, cultivar, and cultivation practices. Matcha products on the market range widely in quality, from high-grade ceremonial products to lower-quality powders. In sencha, compositional profiles differ not only according to harvest timing but also according to infusion conditions such as water temperature and steeping time. Gyokuro, a premium shaded tea, is a type of green tea with a particularly high theanine content, just like authentic matcha. The compositional differences are expected to influence the physiological and psychological functions of green tea. For instance, the stress-relieving effects of theanine are modulated not only by its concentration but also by its interactions with coexisting compounds such as caffeine and catechins. Similarly, the bioavailability and physiological activities of catechins may be altered by coexisting theanine and caffeine. This narrative review focuses on compositional variability and interactions among major bioactive compounds in Japanese green tea and discusses how these factors may influence their functional properties. Full article

(This article belongs to the Section Natural Products Chemistry)

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40 pages, 2794 KB

Open AccessReview

Recycling of End-of-Life Crystalline Silicon Photovoltaic Modules: A Comprehensive Review of Technologies, Challenges, and Prospects

by Huide Fu, Yang Zhou and Bing Bai

Molecules 2026, 31(16), 2933; https://doi.org/10.3390/molecules31162933 - 21 Aug 2026

Viewed by 582

Abstract

As global photovoltaic (PV) installation capacity grows rapidly, the environmental pollution and resource waste from the large-scale end-of-life (EOL) wave have drawn increasing attention. Traditional disposal methods such as landfilling and incineration are no longer viable, making green recycling a logical path for [...] Read more.

As global photovoltaic (PV) installation capacity grows rapidly, the environmental pollution and resource waste from the large-scale end-of-life (EOL) wave have drawn increasing attention. Traditional disposal methods such as landfilling and incineration are no longer viable, making green recycling a logical path for the PV industry. This paper reviews recent progress in the disassembly and recycling of EOL crystalline silicon (c-Si) PV modules. It first describes the structural material composition of c-Si PV modules and summarizes global recycling policies and regulatory frameworks. It then analyzes the mechanisms and process parameters of major delamination technologies, including mechanical crushing, pyrolysis, thermal cutting, high-voltage pulse fragmentation, solvent-based approaches, and laser peeling. Methods for purifying silicon and recovering precious metals such as silver and copper are also covered. Finally, key challenges in the recycling field and future development trends are discussed, with the aim of supporting the advancement of c-Si PV recycling technologies and the sustainable development of related industrial chains. Full article

(This article belongs to the Special Issue 5th Anniversary of the "Applied Chemistry" Section)

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16 pages, 4239 KB

Open AccessArticle

Multivariate Statistical Evaluation of Ginseng Quality and Antioxidant Activity

by Menglin Yuan, Feilong Yang, Jie Li, Haidan Zou, Yang Liu and Heyuan Jiang

Molecules 2026, 31(16), 2932; https://doi.org/10.3390/molecules31162932 - 21 Aug 2026

Viewed by 342

Abstract

The composition of ginsenosides is closely associated with antioxidant activity, but the effects of variety and growth year on the accumulation of individual ginsenosides and their quantitative relationships with free radical scavenging activity remain unclear. In this study, six ginsenosides (Rb1, Rb2, Rc, [...] Read more.

The composition of ginsenosides is closely associated with antioxidant activity, but the effects of variety and growth year on the accumulation of individual ginsenosides and their quantitative relationships with free radical scavenging activity remain unclear. In this study, six ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1) in cultivated ginseng (Panax ginseng C. A. Mey.) and American ginseng (Panax quinquefolius L.) were quantified by HPLC, combined with DPPH and ABTS assays, and systematically analyzed using PCA, OPLS-DA, HCA, and PLSR. The results showed that variety exerted a much greater influence than growth year. American ginseng contained significantly higher levels of PPD-type ginsenosides (Rb1, Rd, Rc), while Rg1 was more abundant in cultivated ginseng. OPLS-DA clearly distinguished the two varieties based on ginsenoside profiles, with Rc, Rb1, and Rd identified as key marker ginsenosides (VIP > 1). Ginsenoside extracts showed scavenging abilities against both DPPH and ABTS. However, the PLSR model only successfully yielded predictive capability for DPPH. The poor prediction for ABTS suggested that ABTS scavenging may be attributed to other untested constituents in the extracts. This study provides a robust basis for variety-oriented quality control and antioxidant efficacy evaluation in ginseng products. Full article

(This article belongs to the Section Food Chemistry)

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25 pages, 4773 KB

Open AccessArticle

Comprehensive Evaluation of Peonidin: Antioxidant and Multi-Enzyme Inhibitory Abilities with Molecular Docking Insights

by Hasan Karageçili, Emrah Yerlikaya, Adem Ertürk, Kübra Aslan, Hülya Akıncıoglu and İlhami Gülçin

Molecules 2026, 31(16), 2931; https://doi.org/10.3390/molecules31162931 - 21 Aug 2026

Viewed by 438

Abstract

Anthocyanins are water-soluble plant pigments. They give many plants, fruits, vegetables, and cereal kernels their red, purple, and blue colors. This research aims to reveal the biological properties of peonidin as an anthocyanin. To comprehend the antioxidant capabilities of peonidin, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical [...] Read more.

Anthocyanins are water-soluble plant pigments. They give many plants, fruits, vegetables, and cereal kernels their red, purple, and blue colors. This research aims to reveal the biological properties of peonidin as an anthocyanin. To comprehend the antioxidant capabilities of peonidin, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS^•+), N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD^•+), and 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH^•) scavenging, Fe³⁺-2,4,6-tris(2-pyridyl)-s-triazine (TPTZ), and Cu²⁺ reducing assays were recorded. The IC₅₀ values for peonidin against ABTS^•+, DMPD^•+ and DPPH^• scavenging capabilities were determined to compare with standard antioxidants. ABTS^•+ radical scavenging activity of peonidin had an IC₅₀ value of 15.40 μg/mL, while the IC₅₀ values for BHA, BHT, Trolox, and α-Tocopherol were 12.82, 11.78, 12.67, and 10.83 μg/mL, respectively. DPPH radical scavenging activity of peonidin had an IC₅₀ value of 41.63 μg/mL, while the IC₅₀ values for BHA, BHT, Trolox, and α-Tocopherol were 8.45, 23.10, 6.30, and 18.73 μg/mL, respectively. Enzyme inhibition was studied to investigate the effects of peonidin. The K_i values of peonidin were 114.33, 63.02, 2.99, 9.76, and 15.14 nM toward hCA I, hCA II, AChE, BChE, and α-glycosidase enzymes, respectively. Furthermore, peonidin’s interactions with target enzymes BChE, hCA I, hCA II, AChE, and α-glycosidase were investigated by molecular docking. The results suggest that antioxidant-rich peonidin is a plant-based compound with potential use in the treatment of glaucoma, Alzheimer’s disease, and diabetes. Full article

(This article belongs to the Special Issue Bioactives and Functional Ingredients in Foods, 3rd Edition)

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31 pages, 7408 KB

Open AccessArticle

Pectinase Immobilization on Porous Polyamide Microparticles: Characterization, Operational Stability and Application in Wine Clarification

by Sandra C. Oliveira, Nadya V. Dencheva and Zlatan Z. Denchev

Molecules 2026, 31(16), 2930; https://doi.org/10.3390/molecules31162930 - 21 Aug 2026

Viewed by 310

Abstract

Lyophilized pectinase from Aspergillus niger (PeL) was immobilized onto polyamide 6 (PA6) microparticles (MPs) through an adsorption-based procedure within the pH range of 5–8, yielding four PeL@PA6 complexes. In contrast to commercial enological preparations that are complex enzymatic cocktails with unspecified exact compositions, [...] Read more.

Lyophilized pectinase from Aspergillus niger (PeL) was immobilized onto polyamide 6 (PA6) microparticles (MPs) through an adsorption-based procedure within the pH range of 5–8, yielding four PeL@PA6 complexes. In contrast to commercial enological preparations that are complex enzymatic cocktails with unspecified exact compositions, the use of PeL with known specific activity enabled a more reliable evaluation and improvement of the immobilization process and of the structure–activity relationships of the resulting biocatalysts. Thermogravimetric analysis demonstrated better thermal stability of the PeL@PA6 complexes compared to neat PA6 MPs. UV-CD studies revealed that the secondary structure and conformational stability of PeL before and after immobilization were strongly pH-dependent, with maximum stability observed at pH 6–7. All four PeL@PA6 complexes retained significant catalytic activity and showed good tolerance to ethanol-rich media relevant to enological applications. Kinetic analysis indicated increased apparent K_m values after immobilization, suggesting diffusional limitations associated with the porous PA6 support. Clarification experiments of industrial white and rosé wine musts confirmed the practical applicability of the immobilized system. All PeL@PA6 complexes preserved the color and phenolic integrity of the musts, displayed good operational stability during reuse, and exhibited higher long-term storage stability than the free enzyme. These results demonstrate that PA6 MPs are promising supports for pectinase immobilization in wine clarification and related biotechnological applications. Full article

(This article belongs to the Special Issue Recent Advances in Immobilization of Bioactive Molecules in Polymeric Materials)

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19 pages, 1725 KB

Open AccessArticle

Optimization of Polyphenol Extraction Process from Yunnan-Grown Olives and Analysis of Taste Capacity Using Response Surface Methodology

by Hongyang Pan, Zhaojun Wang and Jie Chen

Molecules 2026, 31(16), 2929; https://doi.org/10.3390/molecules31162929 - 21 Aug 2026

Viewed by 293

Abstract

This study aimed to optimise polyphenol extraction from Yunnan-grown olives (Canarium album), investigate key factors influencing taste capacity and their underlying mechanisms, and to provide technical support for industrial scale-up. Initial single-factor experiments assessed the effects of seven operational parameters on [...] Read more.

This study aimed to optimise polyphenol extraction from Yunnan-grown olives (Canarium album), investigate key factors influencing taste capacity and their underlying mechanisms, and to provide technical support for industrial scale-up. Initial single-factor experiments assessed the effects of seven operational parameters on extraction yield and sensory quality. Subsequently, ethanol concentration, extraction temperature, extraction time, and pH were selected as independent variables to optimize the process and validate the model via a Central Composite Design (CCD), using total polyphenol extraction yield and taste capacity as response values. The results showed that single-factor experiments identified 60% ethanol as the optimal solvent, with enhanced extraction efficiency at a 3 h extraction time, a temperature of 50 °C, and a pH of 3. Quantitative analysis during single-factor experiments revealed strong correlations between extraction yield and taste capacity (r > 0.88). The response surface model exhibited a high goodness-of-fit; the impact of individual factors on the extraction yield followed the order of extraction temperature > extraction time > ethanol concentration > pH, whereas the order for taste capacity was extraction temperature > extraction time > pH > ethanol concentration. Under optimal process conditions, the total polyphenol extraction yield reached 216.38 ± 3.60 mg/g, with a taste capacity of 1.27 ± 0.02, showing no significant difference between the predicted and experimental values (p > 0.05). By synergistically regulating extraction parameters, the optimized process successfully balances efficient polyphenol dissolution with desirable taste characteristics. These findings provide a solid scientific reference for the value-added development of Yunnan-grown olive polyphenols. Full article

(This article belongs to the Special Issue Innovative Analytical Approaches for the Isolation and Characterization of Drugs, Metabolites and Natural Bioactive Compounds)

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24 pages, 2589 KB

Open AccessReview

Plant-Based Approaches for Inhibition of Advanced Glycation End Products Formation: Dietary Polyphenols

by Seray Akalin-Saygili and Aylin Ayaz

Molecules 2026, 31(16), 2928; https://doi.org/10.3390/molecules31162928 - 21 Aug 2026

Viewed by 532

Abstract

Advanced glycation end products arise during thermal processing and endogenous metabolism, contributing to oxidative stress, inflammation, and the progression of chronic diseases. Dietary polyphenols have emerged as promising advanced glycation end product (AGE) inhibitors through antioxidant activity, carbonyl trapping, metal chelation, and modulation [...] Read more.

Advanced glycation end products arise during thermal processing and endogenous metabolism, contributing to oxidative stress, inflammation, and the progression of chronic diseases. Dietary polyphenols have emerged as promising advanced glycation end product (AGE) inhibitors through antioxidant activity, carbonyl trapping, metal chelation, and modulation of inflammatory pathways. This review summarizes current evidence on the effects of polyphenols in food systems and highlights how different polyphenol subclasses vary in their antiglycation potential depending on chemical structure, food matrix, and cooking conditions. Although experimental studies consistently demonstrate inhibitory effects, the translation to humans remains limited by low bioavailability, metabolic transformation, and heterogeneous analytical methods. Standardized AGE measurements are needed to improve mechanistic insight, and evaluations of dose–response relationships are needed to clarify their relevance in real-world diets. Future research should prioritize long-term human studies and practical culinary strategies to determine whether polyphenol-rich foods can meaningfully reduce dietary AGE exposure and support chronic disease prevention. Full article

(This article belongs to the Special Issue Featured Review Papers in Food Chemistry—2nd Edition)

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24 pages, 2969 KB

Open AccessArticle

Passiflora edulis Seed Oil in an Experimental Zebrafish Model of Hyperglycemia During Embryogenesis: Evaluation of Free Glucose Modulation, Oxidative Stress, Antioxidant Gene Expression, and Developmental Safety

by Elaine L. S. S. Mendonça, Felipe C. Silva, José W. A. C. Silva, Rafael L. B. Oliveira, Igor F. P. Silva, Henrique F. Goulart, Antônio E. G. Santana, João I. Soletti, Alane C. M. Oliveira, Marília O. F. Goulart and Jadriane A. Xavier

Molecules 2026, 31(16), 2927; https://doi.org/10.3390/molecules31162927 - 21 Aug 2026

Viewed by 363

Abstract

Passiflora edulis seed oil (PESO) is a rich source of lipophilic bioactive compounds with potential to modulate oxidative stress and free glucose levels. This preclinical study aimed to evaluate the toxicological profile, antioxidant and glucose-modulating effects of PESO using hyperglycemic Danio rerio embryos [...] Read more.

Passiflora edulis seed oil (PESO) is a rich source of lipophilic bioactive compounds with potential to modulate oxidative stress and free glucose levels. This preclinical study aimed to evaluate the toxicological profile, antioxidant and glucose-modulating effects of PESO using hyperglycemic Danio rerio embryos (AB strain). PESO was chemically characterized by GC-FID/GC-MS after derivatization to fatty acid methyl esters. In animal studies, the median lethal concentration (LC₅₀) of PESO at 96 h post-exposure (hpe) was determined using concentrations ranging from 12.5 to 400 μg/mL, and sublethal concentrations corresponding to 1/10 and 1/20 of the LC₅₀ were selected for further investigations, including survival rate up to 144 hpe, continuous and pulsatile hyperglycemia assays (total free glucose was quantified in washed embryo or larval homogenates using an Accu-Chek Active^® glucometer) (Roche Diabetes Care GmbH, Mannheim, Germany), total reactive oxygen species (ROS) production, and antioxidant gene expression at 96 hpe. Data were analyzed by nonlinear regression or analysis of variance followed by appropriate post hoc tests, with significance set at p ≤ 0.05. Chemical characterization identified linoleic acid (C18:2) as the predominant fatty acid. PESO exhibited an LC₅₀ of 191.1 µg/mL. PESO at 9.5 and 19.1 µg/mL achieved embryonic survival above 85% and reduced total free glucose values in washed embryo or larval homogenates under pulsatile and continuous hyperglycemic conditions (p ≤ 0.05), although less effective than insulin (0.1 U/mL). PESO attenuated ROS production by 2% (w/v) glucose (p ≤ 0.05). PESO treatment was associated with distinct concentration-related expression profiles among the selected antioxidant-related genes: sod1 and cat expression increased at both concentrations, sod2, gpx1a, and gsr increased at 19.1 µg/mL, and nfe2l2a increased at 9.5 µg/mL (p ≤ 0.05). At the selected sublethal concentrations, PESO showed low embryotoxicity and was associated with reduced total free glucose values, partial attenuation of ROS accumulation, and changes in selected antioxidant-related transcripts in embryos exposed to hyperglycemic conditions. Full article

(This article belongs to the Special Issue Bioactive Compounds: Applications and Benefits for Human Health, 2nd Edition)

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18 pages, 2775 KB

Open AccessArticle

Ultrasonic-Assisted Heterogeneous Fenton-like (UHEF) Pretreatment of Eucalyptus Sawdust for Enhanced Enzymatic Hydrolysis

by Han Zhang, Cuixian Peng, Xiaoguo Wang, Ping Li, Wei Tan and Shujie Wang

Molecules 2026, 31(16), 2926; https://doi.org/10.3390/molecules31162926 - 21 Aug 2026

Viewed by 302

Abstract

Ultrasonic-assisted heterogeneous Fenton-like (UHEF) pretreatment is an emerging strategy that overcomes the limitations of traditional homogeneous Fenton systems while enhancing the efficiency of lignocellulosic biomass processing. In this study, we constructed a UHEF system employing iron-loaded zeolite as a heterogeneous catalyst to pretreat [...] Read more.

Ultrasonic-assisted heterogeneous Fenton-like (UHEF) pretreatment is an emerging strategy that overcomes the limitations of traditional homogeneous Fenton systems while enhancing the efficiency of lignocellulosic biomass processing. In this study, we constructed a UHEF system employing iron-loaded zeolite as a heterogeneous catalyst to pretreat eucalyptus sawdust (ES). Process conditions were optimized using response surface methodology (RSM) with a central composite design (CCD), yielding a maximum reducing sugar production of 441.45 mg/g. We systematically investigated the mechanism by which UHEF pretreatment enhances the enzymatic hydrolysis of ES through compositional analysis, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), cross-polarization magic-angle spinning carbon-13 nuclear magnetic resonance (CP/MAS ¹³C NMR), and scanning electron microscopy (SEM). Additionally, recovery and recycling experiments were conducted to evaluate the reusability of the iron-loaded zeolite. XRD, XPS, and ICP-OES were further used to verify the crystalline structure, surface Fe chemical states, and Fe loading of the catalyst, and Fe leaching was quantified for each reuse cycle. The results demonstrated that UHEF pretreatment effectively removed lignin and hemicellulose from ES, disrupted the cellulose crystalline structure, and generated numerous grooves on the substrate surface. These modifications increased the effective adsorption of cellulase and enhanced reducing sugar production to 4.32 times that of raw eucalyptus sawdust (RES). Although the recycling experiments indicated that the stability of the iron-loaded zeolite requires further improvement, the catalyst retained a certain degree of reusability over four consecutive cycles. These findings demonstrate that UHEF pretreatment is a promising approach with broad application prospects in lignocellulosic biorefinery, consistent with recent advances in advanced oxidation processes for biomass valorization. Full article

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20 pages, 3830 KB

Open AccessArticle

Polyphenol-Rich Euterpe oleracea Mart. Seed Extract Improves High-Fat-Diet-Induced MASLD Through Modulation of Hepatic Mitochondrial Respiration, Biogenesis, and Redox Homeostasis

by Dafne L. Beserra-Silva, Julia F. Gouveia, Beatriz C. de Oliveira, Mariana A. Cavalheira, Natália P. A. Nogueira, Marcia Cristina Paes, Simone V. da Silva, Ana Lucia R. Nascimento, Jorge José de Carvalho, Dayane T. Ognibene, Cristiane A. da Costa, Graziele F. de Bem and Angela C. Resende

Molecules 2026, 31(16), 2925; https://doi.org/10.3390/molecules31162925 - 21 Aug 2026

Viewed by 437

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, characterized by hepatic steatosis, mitochondrial dysfunction, and oxidative stress. Food-derived polyphenols are promising ingredients that modulate cellular metabolism and redox balance. Açaí (Euterpe oleracea Mart.) seed, a polyphenol-rich agro-industrial [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, characterized by hepatic steatosis, mitochondrial dysfunction, and oxidative stress. Food-derived polyphenols are promising ingredients that modulate cellular metabolism and redox balance. Açaí (Euterpe oleracea Mart.) seed, a polyphenol-rich agro-industrial by-product, has shown hepatoprotective potential; however, no previous study has comprehensively evaluated its effects on key mitochondrial functions in experimental MASLD. Therefore, this study investigated whether açaí seed extract (ASE), administered alone or in combination with physical training, could improve hepatic mitochondrial respiration, biogenesis, ultrastructural integrity, and redox homeostasis in HF diet-fed Sprague–Dawley rats. Male rats were fed a control or HF diet for 16 weeks and treated with ASE (200 mg/kg/day), aerobic training, or both during the final six weeks. ASE reduced hepatic steatosis by approximately 52% compared with the HF group, improved mitochondrial ultrastructure, increased the expression of the mitochondrial biogenesis regulators PGC-1α and NRF-1, with a 3-fold increase in PGC-1α mRNA expression, increased TFAM immunoreactivity, increased PPARα expression, reduced oxidative stress, and restored lipid-driven mitochondrial respiration. Physical training improved glycemic control and mitochondrial structure, with limited effects on mitochondrial function and redox balance. Combined treatment reduced plasma triglycerides by 41%, increased CPT1α expression, and enhanced carbohydrate-supported mitochondrial respiration. These findings provide mechanistic support for further investigation of açaí seed-derived polyphenols as candidates for nutritional strategies targeting MASLD. Full article

(This article belongs to the Special Issue Green Extraction and Valorization of Bioactive Compounds from Agri-Food Resources)

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16 pages, 9507 KB

Open AccessArticle

Light-Controlled Assembly and Disassembly of Covalent RNA–Protein Conjugates to Control RNA Base Editing

by Alfred Hanswillemenke, Tim Stefan Berneiser, Marius Blackholm, Johann Kaiser, Anna Sofia Imrich, Karthika Devi Kiran Kumar, Hayase Hakariya and Thorsten Stafforst

Molecules 2026, 31(16), 2924; https://doi.org/10.3390/molecules31162924 - 21 Aug 2026

Viewed by 592

Abstract

Self-labeling enzymes, like SNAP-, CLIP- and Halo-tag have found wide application in biology, biochemistry, materials science and bioengineering. For example, they have been applied with high versatility to rewrite genetic information inside the living cell by providing rationally programmable RNA-targeting strategies of protein-based [...] Read more.

Self-labeling enzymes, like SNAP-, CLIP- and Halo-tag have found wide application in biology, biochemistry, materials science and bioengineering. For example, they have been applied with high versatility to rewrite genetic information inside the living cell by providing rationally programmable RNA-targeting strategies of protein-based effectors. Such approaches benefit from the engineering capability of the small molecule-based self-labeling moieties. Here, we further engineered that approach to control RNA-targeting by light. Specifically, we combined two orthogonal self-labeling enzymes for the recruitment of two distinct fusion proteins to a target RNA inside the living cell and achieved concurrent assembly and disassembly of distinct guide RNA–protein conjugates. We applied this to control RNA base editing and achieved a photo-induced swap of two distinct editing events. Overall, this work describes new ways for tool development, RNA imaging, and transcript engineering. Full article

(This article belongs to the Section Chemical Biology)

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6 pages, 161 KB

Open AccessEditorial

Challenges and Opportunities in Food Processing Using Innovative Techniques

by Hanna Kowalska and Mariola Kozłowska

Molecules 2026, 31(16), 2923; https://doi.org/10.3390/molecules31162923 - 21 Aug 2026

Viewed by 257

Abstract

Alongside environmental concerns, the growing consumer demand for foods with high nutritional value, health-promoting properties, and sensory benefits has driven the development of innovative and sustainable food processing technologies [...] Full article

(This article belongs to the Special Issue Advances in Physicochemical Properties of Innovative Food Products During Processing)

17 pages, 3337 KB

Open AccessArticle

An Integrated Two-Stage Strategy for Efficient Lactic Acid Production via Ionic Liquid-Assisted Mechanochemical Pretreatment and Catalytic Conversion

by Zheyuan Zhang, Chuan Li Lee, Jianrong Shan and Haixin Guo

Molecules 2026, 31(16), 2922; https://doi.org/10.3390/molecules31162922 - 21 Aug 2026

Viewed by 322

Abstract

Efficient conversion of cellulose to value-added lactic acid remains challenging because the rigid crystalline structure of cellulose limits its accessibility and subsequent conversion. This study developed an integrated strategy combining ionic liquid-assisted ball milling with catalytic lactic acid production. Ionic liquid type, ball-milling [...] Read more.

Efficient conversion of cellulose to value-added lactic acid remains challenging because the rigid crystalline structure of cellulose limits its accessibility and subsequent conversion. This study developed an integrated strategy combining ionic liquid-assisted ball milling with catalytic lactic acid production. Ionic liquid type, ball-milling time, ionic liquid concentration, and glucose addition were examined during cellulose pretreatment. Among the ionic liquids tested, 1-butyl-3-methylimidazolium acetate ([Bmim][OAc]) provided the highest apparent water-soluble fraction. After 60 min of ball milling with 0.17 M [Bmim][OAc], the apparent water-soluble fraction increased from 5.1% for untreated cellulose to 63.7%, while the crystallinity index decreased from 78.1% to 44.0%. The catalytic stage was then evaluated using D-glucose as a model substrate with rehydrated hydrotalcite (r-HT) in a Ba(OH)₂ medium. The r-HT/Ba(OH)₂ system achieved the highest lactic acid yield of 43.6 C-% at 100 °C for 2 h, compared with 9.1 C-% for r-HT and 38.2 C-% for Ba(OH)₂ alone. These results demonstrate the potential of this integrated strategy to improve cellulose accessibility while enhancing lactic acid formation from glucose, providing a basis for further development of cellulose-to-lactic-acid conversion pathways. Full article

(This article belongs to the Special Issue Advances in Catalytic Conversion of Biomass-Derived Molecules)

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5 pages, 158 KB

Open AccessEditorial

Natural Products: Advances in Isolation, Characterization, Biological Activities, and Plant Protection Applications

by Hazem S. Elshafie

Molecules 2026, 31(16), 2921; https://doi.org/10.3390/molecules31162921 - 21 Aug 2026

Viewed by 277

Abstract

Natural products derived from plants and microorganisms remain promising alternatives to synthetic chemicals and conventional substances across a wide range of fields, including pharmaceuticals, agriculture, and industry. They also play an important role in the development of sustainable biopesticides and biofertilizers. Chemically, natural [...] Read more.

Natural products derived from plants and microorganisms remain promising alternatives to synthetic chemicals and conventional substances across a wide range of fields, including pharmaceuticals, agriculture, and industry. They also play an important role in the development of sustainable biopesticides and biofertilizers. Chemically, natural products can be grouped into overlapping structural and biosynthetic categories, including alkaloids, terpenoids, flavonoids, glycosides, saponins, and polyketides. Each group reflects distinct chemical characteristics and associated biological functions. This overview highlights the main findings from the Molecules Special Issue: “Natural Products: Isolation, Analysis and Biological Activity, 2nd Edition”, focusing on three categories: (i) plant protection, plant health, and plant biotechnology; (ii) functional foods and health-promoting formulations; and (iii) therapeutic natural products and derivatives. Exploring the mechanisms of action of natural products is essential for ensuring safety and optimizing sustainable resource use. This understanding drives critical innovations across drug discovery and materials science. Ultimately, such research reinforces their cross-disciplinary significance for advancing human health and promoting environmental sustainability. Full article

(This article belongs to the Special Issue Natural Products: Isolation, Analysis and Biological Activity, 2nd Edition)

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17 pages, 2542 KB

Open AccessReview

Sweet Woodruff (Galium odoratum L.)—More than Just Coumarin: From Fundamental to Biomass Valorization

by Isabelle Herre and Thomas Stegemann

Molecules 2026, 31(16), 2920; https://doi.org/10.3390/molecules31162920 - 21 Aug 2026

Viewed by 343

Abstract

Galium odoratum (L.) Scop., commonly known as sweet woodruff, is a perennial European woodland herb traditionally used as a medicinal and aromatic plant. Its characteristic sweet, hay-like scent is mainly linked to coumarin, which is formed from glycosidically bound melilotoside precursors during wilting [...] Read more.

Galium odoratum (L.) Scop., commonly known as sweet woodruff, is a perennial European woodland herb traditionally used as a medicinal and aromatic plant. Its characteristic sweet, hay-like scent is mainly linked to coumarin, which is formed from glycosidically bound melilotoside precursors during wilting and drying. However, the phytochemistry of G. odoratum extends beyond coumarin. The species also contains iridoid glycosides, coumarin-related melilotosides, caffeoylquinic acids, flavonoids, and volatile constituents. This review summarizes current knowledge on traditional use, phytochemical constituents, metabolite dynamics, biological and ecological relevance, toxicology, and potential applications. Seasonal variation, organ-specific differences, post-harvest metabolism, and differences in analytical methodology affect analytical interpretation of the available data. Reported biological activities are mainly based on isolated constituents, in vitro studies, animal models, or non-standardized extracts, and no convincing clinical evidence is available for defined G. odoratum preparations. Potential applications require standardized plant material, controlled processing, sustainable sourcing, and safety assessment, while the valorization of processing residues may provide an additional route toward more resource-efficient utilization of the species. Overall, G. odoratum should be regarded as a chemically diverse species rather than merely as a source of coumarin aroma. Full article

(This article belongs to the Special Issue Applications of Agro-Industrial By-Products in Health and Beauty: Innovative Strategies and Applications)

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18 pages, 2309 KB

Open AccessArticle

Enzymatic Degradation of Cryptosporidium spp. Oocysts: A Combined In Silico and In Vitro Study

by Débora Castro Toledo de Souza, Ana Carolina Silva, Adriane Toledo Batista da Silva, Ruth Celestina Condori Mamani, Júlia Gomes de Carvalho Jorge, Carolina Magri Ferraz, Fábio Ribeiro Braga, Jackson Victor de Araújo and Filippe Elias de Freitas Soares

Molecules 2026, 31(16), 2919; https://doi.org/10.3390/molecules31162919 - 21 Aug 2026

Viewed by 376

Abstract

Proteases are widely studied hydrolases as “green technologies” for degrading structures within complex matrices, although combining different classes poses challenges for catalytic stability. To the best of our knowledge, this is the first study to specifically evaluate the biochemical control of Cryptosporidium spp. [...] Read more.

Proteases are widely studied hydrolases as “green technologies” for degrading structures within complex matrices, although combining different classes poses challenges for catalytic stability. To the best of our knowledge, this is the first study to specifically evaluate the biochemical control of Cryptosporidium spp. oocysts using plant- and microbial-derived proteases. This study evaluated the compatibility and sanitizing potential of the microbial serine protease subtilisin Carlsberg (HPF-1SCA) and the plant cysteine protease papain (1PPP), both individually and in a 15% (w/v) combination, hypothesizing a synergistic effect due to their distinct catalytic specificities, as a potential biochemical approach to reduce contamination by these zoonotic protozoa of global importance, which are highly resilient to conventional disinfectants. The experimental design comprised five distinct treatment groups: a negative control (distilled water), a positive chemical control (0.04% v/v NaClO), treatment with isolated papain (15% w/v), treatment with isolated microbial HPF formulation (15% w/v), and a combined treatment using both enzymes simultaneously (15% w/v each). Concurrently, an in silico molecular docking investigation was conducted to elucidate the predicted binding scores, structural compatibility, and preferential binding mechanisms of these enzymes toward the Cryptosporidium Oocyst Wall Protein (COWP). In vitro compatibility assays revealed an immediate antagonistic effect due to mutual proteolysis, reducing overall proteolytic activity by 45% after 72 h. Despite this antagonism, the enzyme mixture (G5) and the isolated microbial protease (G4) achieved a 93% reduction in oocysts, equivalent to the conventional 0.04% NaClO treatment (G2), while papain (G3) achieved 65%. All these results represented statistically significant efficacy (p < 0.01) compared to the negative control (G1). In silico molecular docking studies provided a structural predictive basis for the experimental data, suggesting that subtilisin Carlsberg (HPF-1SCA) exhibits more favorable predicted binding scores and structurally compatible interfaces, compared to papain, particularly toward the major oocyst structural proteins COWP8 (estimated ΔG = −15.2 kcal·mol⁻¹) and COWP6 (estimated ΔG = −13.3 kcal·mol⁻¹). This provides robust evidence for initial target recognition and molecular anchoring, although these static models do not definitively confirm catalytically productive cleavage conformations. In summary, this in vitro proof-of-concept demonstrates that microbial proteases show promise for the biochemical destabilization of oocysts without generating toxic chlorinated byproducts. While these baseline findings align with the One Health concept, future field-scale validations assessing enzyme stability under variable environmental conditions and in vivo infectivity assays are required before practical application in sanitation protocols. Full article

(This article belongs to the Special Issue Chemical Compounds or Agents Against Parasites, Bacteria, and Neglected Tropical Diseases)

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62 pages, 5096 KB

Open AccessReview

Chemical Composition, Biological Activities and Application of Lupinus angustifolius in Cosmetics and Food Industry

by Maciej Jakobina, Renata Galek and Marta Preisner

Molecules 2026, 31(16), 2918; https://doi.org/10.3390/molecules31162918 - 20 Aug 2026

Viewed by 368

Abstract

Lupins have been cultivated since ancient times. Poland ranks second in the world in terms of lupin cultivation area (second only to Australia), particularly for narrow-leaved lupin. It is used in various industries. The purpose of this review is to analyze data on [...] Read more.

Lupins have been cultivated since ancient times. Poland ranks second in the world in terms of lupin cultivation area (second only to Australia), particularly for narrow-leaved lupin. It is used in various industries. The purpose of this review is to analyze data on the chemical composition of narrow-leaved lupin in comparison with other species of this genus, as well as to identify its potential applications. The literature data characterize narrow-leaved lupin in terms of its content of protein, lectins, fat, carotenoids, phytosterols, fiber, sugars, alkaloids, vitamins, flavonoids, phenolic compounds, volatile organic compounds, and micro- and macronutrients. Due to its interesting qualitative and quantitative composition, this species may play a significant role in human nutrition—not only as an alternative source of protein, but above all as a source of health-promoting compounds. Studies conducted on humans and animals have demonstrated a wide range of biological effects, including anti-inflammatory, antioxidant and cholesterol-lowering effects. In addition, in vitro studies suggest anticancer effects. Among the tangible outcomes of research and commercialization efforts is the availability on the consumer market of food and cosmetic products containing lupin. Due to its properties, this species has a wide range of applications. However, to meet the requirements of various industrial sectors, a collaborative approach is necessary among plant breeders, scientists, and industry representatives working to improve this species. Only through joint efforts can the use of narrow-leaved lupin be expanded. Full article

(This article belongs to the Section Natural Products Chemistry)

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26 pages, 17099 KB

Open AccessArticle

Hydrogen-Rich Gas Production from Municipal Solid Waste via Integrated Pyrolysis and Catalytic Steam Reforming over Ni/Al₂O₃ Catalyst

by Ivan Pedro Lazzarotto, Oscar de Almeida Neuwald, Lucas David Biondo, Daniele Perondi, Christian Manera and Marcelo Godinho

Molecules 2026, 31(16), 2917; https://doi.org/10.3390/molecules31162917 - 20 Aug 2026

Viewed by 279

Abstract

The transition to a hydrogen-based economy requires efficient and sustainable technologies to convert waste into clean energy carriers. This study investigates the production of hydrogen-rich gas through the integrated pyrolysis steam reforming (PSR) and integrated pyrolysis (PYR) and catalytic steam reforming (PCSR) of [...] Read more.

The transition to a hydrogen-based economy requires efficient and sustainable technologies to convert waste into clean energy carriers. This study investigates the production of hydrogen-rich gas through the integrated pyrolysis steam reforming (PSR) and integrated pyrolysis (PYR) and catalytic steam reforming (PCSR) of real municipal solid waste (MSW). PCSR experiments were conducted in a two-stage series reactor system: an initial pyrolysis stage at 500 °C followed by a catalytic steam reforming stage at 900 °C over a commercial Ni/Al₂O₃ catalyst (9.8 wt.% Ni). Three real MSW samples from the Serra Gaúcha region (Brazil) were evaluated: organic-rich (A), polymeric-rich (B), and a mixed real collection fraction (C). Gas yields from PYR to PCSR increased from 0.44 to 1.18 Nm³·kgMSW⁻¹, from 0.66 to 1.54 Nm³·kgMSW⁻¹, and from 0.35 to 1.50 Nm³·kgMSW⁻¹ for (A), (B), and (C) samples, respectively. Hydrogen concentrations of PCSR were between 32% and 39% volume for all samples, with a marked reduction in CH₄ and CO levels due to the promotion of water–gas shift and methane reforming reactions over the nickel active sites. The PCSR process using a Ni/Al₂O₃ catalyst proves to be a highly effective route for maximizing hydrogen production from real MSW, offering a robust technological solution for energy valorization and carbon footprint reduction. Full article

(This article belongs to the Special Issue Synthesis and Applications of Porous Materials as Catalysts and Adsorbents)

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26 pages, 12937 KB

Open AccessArticle

Design, Synthesis, and Structure-Activity Relationships of Novel Piperidine-Fused Imidazolone ClpP Activators as Potential Anti-Cancer Agents

by Shanshan Chen, Xinyi Lin, Min Guo, Ruqi Lei, Beijing Chen, Yubo Zhou, Aijun Qiao, Qi Huang and Mingliang Wang

Molecules 2026, 31(16), 2916; https://doi.org/10.3390/molecules31162916 - 20 Aug 2026

Viewed by 378

Abstract

Caseinolytic protease P (ClpP) is essential for maintaining mitochondrial protein homeostasis, and its activation has emerged as an attractive cancer therapeutic strategy. However, ONC201 is currently the only approved ClpP activator, and its low potency leads to high clinical doses, driving an urgent [...] Read more.

Caseinolytic protease P (ClpP) is essential for maintaining mitochondrial protein homeostasis, and its activation has emerged as an attractive cancer therapeutic strategy. However, ONC201 is currently the only approved ClpP activator, and its low potency leads to high clinical doses, driving an urgent demand for highly potent agents. In this study, utilizing a ring-opening-based molecular simplification strategy, we identified a class of activators based on a novel piperidine-fused imidazolone scaffold. Through side-chain optimization, we ultimately obtained CLPP-3036 as a highly potent compound. CLPP-3036 exhibits nanomolar enzymatic potency (EC₅₀ = 6.02 nM, 146-fold more potent than ONC201) and excellent antiproliferative activity (MV4-11 IC₅₀ = 1.13 nM). Importantly, CLPP-3036 demonstrates significantly superior inhibitory activity compared to ONC201 across multiple hematologic and solid tumor cell lines, such as Raji cells (IC₅₀ = 9.8 nM, nearly 1260-fold more potent). Furthermore, CLPP-3036 promotes the degradation of ClpP substrate proteins and effectively triggers apoptosis in MV4-11 cells. Collectively, CLPP-3036 is a potent piperidine-fused imidazolone ClpP activator and represents a promising lead compound worthy of further study. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Evaluation of Medicinal Potential Compounds—2nd Edition)

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42 pages, 31559 KB

Open AccessReview

Oral Antidiabetic Agents: From Routine Quality Control to Bioanalysis

by Ana-Maria Toma, Larisa Păduraru, Romeo Petru Dobrin, Nela Bibire, Mădălina Vieriu and Mihai Apostu

Molecules 2026, 31(16), 2915; https://doi.org/10.3390/molecules31162915 - 20 Aug 2026

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Abstract

Diabetes mellitus represents a growing global health challenge, establishing oral antidiabetic drugs as a therapeutic class of paramount importance. Consequently, to ensure drug safety, therapeutic efficacy, and accurate therapeutic drug monitoring, robust, selective and highly reproducible analytical methods are indispensable. This review provides [...] Read more.

Diabetes mellitus represents a growing global health challenge, establishing oral antidiabetic drugs as a therapeutic class of paramount importance. Consequently, to ensure drug safety, therapeutic efficacy, and accurate therapeutic drug monitoring, robust, selective and highly reproducible analytical methods are indispensable. This review provides a comprehensive overview of instrumental analytical techniques developed between 1985 and 2026 for quantifying oral antidiabetic agents. Based on a literature search across major databases—including PubMed, ScienceDirect and Springer—we systematically evaluated the application of UV-VIS spectrophotometry, liquid chromatography, and advanced electroanalytical methods. The reviewed literature encompasses methodologies ranging from routine quality control of bulk powders and pharmaceutical formulations to complex bioanalytical and pharmacokinetic applications. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) emerged as the gold standard for precise bioanalysis due to its superior selectivity and sensitivity in complex biological matrices. Conversely, UV-VIS spectrophotometry and electrochemical methods remain highly relevant for cost-effective routine quality control in industrial manufacturing. Methodologies are categorized by drug therapeutic class, including biguanides, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, meglitinides, highlighting key validation parameters such as linearity, accuracy, and limits of detection. Finally, this review outlines future directions in the field of antidiabetic drug quantification. Full article

(This article belongs to the Section Analytical Chemistry)

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40 pages, 2378 KB

Open AccessReview

Quercetin as a Multifunctional Flavonol: Molecular Insights and Therapeutic Applications

by Florina Grumăzescu (Bonifate), Andra-Monica Anghel (Ştefan), Anca Lupu, Elena Enachi, Elena-Lăcrămioara Lisă and Camelia Diaconu

Molecules 2026, 31(16), 2914; https://doi.org/10.3390/molecules31162914 - 20 Aug 2026

Cited by 1 | Viewed by 413

Abstract

Quercetin is one of the most abundant plant flavonoids and an intensively studied bioactive compound belonging to the class of functional heterocyclic compounds with outstanding biological activities, due to its numerous biological, pharmacological and therapeutic effects. This paper presents the main information on [...] Read more.

Quercetin is one of the most abundant plant flavonoids and an intensively studied bioactive compound belonging to the class of functional heterocyclic compounds with outstanding biological activities, due to its numerous biological, pharmacological and therapeutic effects. This paper presents the main information on the chemical structure, dietary sources, absorption, metabolism and bioavailability of quercetin, highlighting the role of the intestinal microbiota in the formation of metabolites responsible for an important part of its effects. The limitations related to stability and bioavailability are analyzed as well as modern formulation strategies and advanced delivery systems aimed at improving the efficacy of the compound. The major biological activities of quercetin are also summarized, including antioxidant, anti-inflammatory, immunomodulatory, antiviral, cardioprotective, neuroprotective, metabolic and anticancer effects. Unlike previous reviews, which have generally addressed these topics separately, the present work integrates the gut-microbiota-mediated metabolism, cellular senescence, advanced delivery systems, combined therapies, and safety and regulatory considerations within a unified translational framework. Overall, this review emphasizes the need to relate the multifunctional biological potential of quercetin to its pharmacokinetic limitations, formulation performance and clinically achievable exposure while highlighting the need for standardized formulations and further clinical studies to validate its therapeutic benefits. Full article

(This article belongs to the Special Issue Functional Heterocyclic Compounds with Outstanding Biological Activities)

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25 pages, 1315 KB

Open AccessArticle

NMR Profiling of European Oak Honeydew Honeys: Saccharide Diversity and Geographical Differentiation

by Dessislava Gerginova, María del Carmen Seijo Coello, Nikola Jovanović, Marco Ciulu and Svetlana Simova

Molecules 2026, 31(16), 2913; https://doi.org/10.3390/molecules31162913 - 20 Aug 2026

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Abstract

Although European oak honeydew honeys have a similar botanical origin, it is unclear if their chemical composition reflects their geographical origin. Sixty samples from Bulgaria, Germany, Greece, Italy, North Macedonia, Romania, Serbia, and Spain were analyzed using semiquantitative ¹³C nuclear magnetic resonance [...] Read more.

Although European oak honeydew honeys have a similar botanical origin, it is unclear if their chemical composition reflects their geographical origin. Sixty samples from Bulgaria, Germany, Greece, Italy, North Macedonia, Romania, Serbia, and Spain were analyzed using semiquantitative ¹³C nuclear magnetic resonance (NMR) spectroscopy. The protected designation of origin (PDO) Strandzha honey was compared to honey from other regions in Bulgaria. The profiles included 25 identified constituents, 21 saccharides, and 16 reproducible unidentified signals. Statistical analysis differentiated country groups through combinations of variables rather than a single marker. A decision tree based on nigerose, fructose, melezitose, panose, sucrose, and one unidentified signal summarized the main differences among the countries. Strandzha honeys exhibited a unique regional profile characterized by higher glucose levels and lower concentrations of several minor saccharides and unidentified signals. Two coordinated saccharide networks revealed that minor sugars fluctuate in linked groups rather than independently. This pattern has not been previously described in European honey. Conventional honeydew-associated indicators varied across the dataset. However, 1-kestose was present in all samples. Nevertheless, its specificity to oak honeydew origin remains unresolved. While extended ¹³C NMR profiling may support geographical characterization, independent validation is required before it can be used for authentication. Full article

(This article belongs to the Special Issue Chemistry, Bioactivity and Authenticity of Sugar-Rich and Fermented Foods and Beverages)

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18 pages, 25727 KB

Open AccessArticle

Latent Fingermark Development Using CVD-Synthesized Two-Dimensional GaS_xTe_1−x Alloy Nanosheets

by Runkai Hu, Jun Zhu, Fang Zhou, Yue Zhou, Shangqi Feng, Ziyin Zhang, Yujing Zhao and Feiya Fu

Molecules 2026, 31(16), 2912; https://doi.org/10.3390/molecules31162912 - 20 Aug 2026

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Abstract

Two-dimensional GaS_xTe_1−x alloy nanosheets with different compositions were synthesized by chemical vapor deposition using GaS and GaTe powders as precursors. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) analyses confirmed their sheet-like morphology and the uniform distribution of [...] Read more.

Two-dimensional GaS_xTe_1−x alloy nanosheets with different compositions were synthesized by chemical vapor deposition using GaS and GaTe powders as precursors. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) analyses confirmed their sheet-like morphology and the uniform distribution of S and Te, while Raman and photoluminescence measurements revealed composition-dependent vibrational and emission characteristics. Te-rich samples exhibited position-dependent emission ranging from the red to the near-infrared region, whereas increasing the S content gradually shifted the emission toward the blue-green region. Among the synthesized samples, GaS_0.9Te_0.1 showed a relatively stable photoluminescence peak near 520 nm and was therefore selected as a fluorescent powder for latent fingermark development. Its performance was evaluated on glass, stainless steel, plastic, and ceramic surfaces and compared with that of silver powder, gold powder, and commercial red fluorescent powder. GaS_0.9Te_0.1 produced clear fluorescent ridge patterns and strong background contrast, particularly on glass, plastic, and white ceramic. The mean contrast across the four substrates reached 25.83, exceeding that of the reference powders. These results demonstrate that GaS_xTe_1−x nanosheets possess tunable optical properties and that GaS_0.9Te_0.1 is a promising fluorescent material for latent fingermark development on non-porous surfaces. Full article

(This article belongs to the Section Nanochemistry)

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25 pages, 3181 KB

Open AccessArticle

Rational Design and Structure–Activity Relationship Analysis of Decalin-Based High-Energy-Density Fuel Molecules

by Ya-Ling Gong and Wen-Ying Li

Molecules 2026, 31(16), 2911; https://doi.org/10.3390/molecules31162911 - 20 Aug 2026

Viewed by 351

Abstract

Decalin, accessible through the hydrogenation of coal-tar-derived naphthalene, is a saturated bicyclic hydrocarbon consisting of two fused cyclohexane rings, and provides a promising platform for high-energy-density fuel (HEDF) design. A systematic library of alkyl- and cycloalkyl-substituted trans-decalin derivatives was constructed to investigate [...] Read more.

Decalin, accessible through the hydrogenation of coal-tar-derived naphthalene, is a saturated bicyclic hydrocarbon consisting of two fused cyclohexane rings, and provides a promising platform for high-energy-density fuel (HEDF) design. A systematic library of alkyl- and cycloalkyl-substituted trans-decalin derivatives was constructed to investigate structure–property relationships involving density, net heat of combustion (NHOC), specific impulse, viscosity, flash point, and thermal/oxidative stability. Minimum C–C and C–H bond dissociation enthalpies were used to comparatively assess thermal and oxidative stability by reflecting initial C–C homolysis and H abstraction tendencies, respectively. Density and volumetric NHOC were governed mainly by molecular compactness and packing efficiency, whereas gravimetric NHOC and specific impulse depended primarily on the H/C ratio and ring strain. The flash point was mainly associated with molecular mass, while viscosity was influenced by molecular mass and molecular architecture. Under the engineering-oriented constraints of viscosity ≤ 16 mPa·s and flash points ≥ 360 K, multi-objective screening identified the spiro four-membered-ring motif, particularly α-S-Cycle4, as providing the best overall property balance. In contrast, the fused three-membered-ring motif showed higher specific impulse but greater susceptibility to initial bond activation, suggesting its potential use as a blending component. This work provides quantitative structure-based guidelines for the rational design of HEDFs. Full article

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

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12 pages, 1716 KB

Open AccessArticle

Synthesis of Non-Steroidal Anti-Inflammatory Drugs Pelubiprofen, Loxoprofen, and Carprofen Through Batch and Continuous-Flow Photo-Favorskii Rearrangement

by Sara Ferrario, Paolo Celestini, Gabriele Rebuzzini, Sergio Rossi and Maurizio Benaglia

Molecules 2026, 31(16), 2910; https://doi.org/10.3390/molecules31162910 - 20 Aug 2026

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Abstract

Novel and efficient total syntheses of the nonsteroidal anti-inflammatory drugs Pelubiprofen and Loxoprofen via a photo-Favorskii rearrangement are reported herein. The key photochemical transformation was optimized under both batch and continuous-flow conditions using a suitably functionalized chloro-phenylpropan-1-one derivative, affording the target 2-arylpropionic acid [...] Read more.

Novel and efficient total syntheses of the nonsteroidal anti-inflammatory drugs Pelubiprofen and Loxoprofen via a photo-Favorskii rearrangement are reported herein. The key photochemical transformation was optimized under both batch and continuous-flow conditions using a suitably functionalized chloro-phenylpropan-1-one derivative, affording the target 2-arylpropionic acid in excellent yield. Implementation under continuous-flow conditions increased process productivity and enabled gram-scale operation. Aerobic oxidation of the benzylic position to the corresponding aldehyde, followed by Claisen–Schmidt condensation with cyclohexanone, afforded Pelubiprofen in 35% overall yield. Alternatively, condensation with cyclopentanone afforded the corresponding α,β-unsaturated enone intermediate, whose selective reduction under flow conditions enabled access to Loxoprofen in 28% overall yield. The versatility of the methodology was further demonstrated through the synthesis of Carprofen, highlighting the broader applicability of the photo-Favorskii rearrangement to the synthesis of APIs through previously unreported synthetic routes. Full article

(This article belongs to the Special Issue New Sights in Stereoselective Synthesis)

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