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Natural and Designed Cyclic Peptides as Potential Antiviral Drugs to Combat Future Coronavirus Outbreaks
Heavy Metals in Particulate Matter—Trends and Impacts on Environment
Protein O-Fucosyltransferases: Biological Functions and Molecular Mechanisms in Mammals
Theoretical Insights into the Impact of Pyrrole and Imidazole Substituents on the BODIPY Chromophore

Journal Description

Molecules

Molecules is the leading international, peer-reviewed, open access journal of chemistry. Molecules is published semimonthly online by MDPI. The International Society of Nucleosides, Nucleotides & Nucleic Acids (IS3NA), the Spanish Society of Medicinal Chemistry (SEQT) and the International Society of Heterocyclic Chemistry (ISHC) are affiliated with Molecules and their members receive a discount on the article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Reaxys, CaPlus / SciFinder, MarinLit, AGRIS, and other databases.
Journal Rank: JCR - Q2 (Biochemistry and Molecular Biology) / CiteScore - Q1 (Organic Chemistry)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.1 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2025).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Sections: published in 25 topical sections.
Testimonials: See what our editors and authors say about Molecules.
Companion journal: Foundations.
Journal Cluster of Chemical Reactions and Catalysis: Catalysts, Chemistry, Electrochem, Inorganics, Molecules, Organics, Oxygen, Photochem, Reactions, Sustainable Chemistry.

Impact Factor: 4.6 (2024); 5-Year Impact Factor: 5.0 (2024)

Imprint Information Journal Flyer Open Access ISSN: 1420-3049

Latest Articles

15 pages, 631 KiB

Open AccessArticle

Recovery of Natural Pyrazines and Alcohols from Fusel Oils Using an Innovative Extraction Installation

by Waldemar Studziński, Michał Podczarski, Justyna Piechota, Marzena Buziak, Myroslava Yakovenko and Yurii Khokha

Molecules 2025, 30(14), 3028; https://doi.org/10.3390/molecules30143028 - 18 Jul 2025

The production of spirits generates significant amounts of waste in the form of fusel oils-previously treated mainly as an environmental problem. This paper presents an innovative installation designed to recover valuable components from this difficult waste. The key achievement is the effective separation [...] Read more.

The production of spirits generates significant amounts of waste in the form of fusel oils-previously treated mainly as an environmental problem. This paper presents an innovative installation designed to recover valuable components from this difficult waste. The key achievement is the effective separation and recovery of pyrazine derivatives-natural aromatic compounds with high utility value in the food, cosmetics and pharmaceutical industries. The designed system allows for the recovery of as much as 98% of pyrazines and isoamyl alcohol and isobutanol fractions with a purity above 96%, which is a significant advance compared to previous disposal methods. The installation was designed to be consistent with the idea of a circular economy, maximizing the use of by-products and minimizing losses. The results of the work indicate that fusel oils, previously perceived as waste, can become a source of valuable secondary raw materials, and the presented solution opens up new possibilities for the sustainable development of the alcohol industry. Full article

22 pages, 1148 KiB

Open AccessReview

Applications and Recent Advances in 3D Bioprinting Sustainable Scaffolding Techniques

by Xianyao Li, Jianyu Ren, Yubo Huang, Li Cheng and Zhengbiao Gu

Molecules 2025, 30(14), 3027; https://doi.org/10.3390/molecules30143027 - 18 Jul 2025

In recent years, with the rapid advancement of 3D printing technology, its applications have expanded across numerous fields. Notably, the fabrication of scaffolds using 3D printing has emerged as a major research focus. Researchers are investigating the properties of various printing materials and [...] Read more.

In recent years, with the rapid advancement of 3D printing technology, its applications have expanded across numerous fields. Notably, the fabrication of scaffolds using 3D printing has emerged as a major research focus. Researchers are investigating the properties of various printing materials and tailoring their uses for specific applications. This article reviews the characteristics and applications of different biomaterials printed by 3D technology, such as gelatin, sodium alginate, and starch, highlighting their contributions to the expanding field of 3D-printed biomaterials. Through the comparison in this review, it can be observed that the starch scaffold not only has a lower price but also can be modified to achieve multifunctionality, better meeting the performance requirements in more fields. Full article

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23 pages, 2993 KiB

Open AccessReview

Recent Research Advances in HER2-Positive Breast Cancer Concerning Targeted Therapy Drugs

by Junmin Li, Xue Li, Ruixin Fu, Yakun Fang, Chunmei Zhang, Bingbing Ma, Yanan Ding, Chuanxin Shi and Qingfeng Zhou

Molecules 2025, 30(14), 3026; https://doi.org/10.3390/molecules30143026 - 18 Jul 2025

Breast cancer is one of the most common malignant tumors among women, which seriously threatens women’s health. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, characterized by poor prognosis, is an aggressive phenotype accounting for 15–20% of all kinds of breast cancers. [...] Read more.

Breast cancer is one of the most common malignant tumors among women, which seriously threatens women’s health. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer, characterized by poor prognosis, is an aggressive phenotype accounting for 15–20% of all kinds of breast cancers. Therefore, it has attracted great interest among researchers in discovering targeted therapy drugs countering HER2, and they have been considered as the pivotal therapeutic regimen for HER2-positive breast cancer patients. Nowadays, large progress has been achieved in HER2-targeted drugs, and this review categorizes them into four types according to the drug action mode, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs), antibody-drug conjugates (ADCs), and bispecific antibodies (bsAbs). The progress of HER2-targeted drugs reflects the discovery of drug targets, the screening of drug compounds, and the modification of antibodies, which offer diverse medical options and better therapeutic benefits for individual patients. In detail, we focus on the indication, administration, efficacy, strengths, and challenges of HER2-targeted drugs, concerning approved drugs and clinical trials. This review aims to provide significant references for the targeted therapeutic regimen and a more precise treatment strategy for HER2-positive breast cancer. Full article

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20 pages, 1136 KiB

Open AccessArticle

Novel N-Alkyl 3-(3-Benzyloxyquinoxalin-2-yl) Propanamides as Antiproliferative Agents: Design, Synthesis, In Vitro Testing, and In Silico Mechanistic Study

by Samar A. Abubshait

Molecules 2025, 30(14), 3025; https://doi.org/10.3390/molecules30143025 - 18 Jul 2025

A series of eleven new N-alkyl 3-(3-benzyloxyquinoxalin-2-yl) propanamides were prepared based on the azide coupling of 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide with a variety of primary and secondary amines and the consequent conjunction of a broad spectrum of lipophile and hydrophile characters to a quinoxaline [...] Read more.

A series of eleven new N-alkyl 3-(3-benzyloxyquinoxalin-2-yl) propanamides were prepared based on the azide coupling of 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide with a variety of primary and secondary amines and the consequent conjunction of a broad spectrum of lipophile and hydrophile characters to a quinoxaline ring system. 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide was produced in a two-step reaction of methyl 3-(3-oxo-3,4-dihydroquinoxalin-2-yl) propanoate with benzyl chloride followed by the hydrazinolysis of the corresponding ester. The antiproliferative activity of the compounds was tested in various cancer cell lines, including PC-3, Hela, HCT-116, and MCF-7; they showed a wide spectrum of activity for most of the tested compounds. Compound 6k exhibited the highest activity, which was comparable to that of doxorubicin, with IC₅₀ (µM) values of 12.17 ± 0.9, 9.46 ± 0.7, 10.88 ± 0.8, and 6.93 ± 0.4 µM compared to 8.87 ± 0.6, 5.57 ± 0.4, 5.23 ± 0.3, and 4.17 ± 0.2 µM for doxorubicin against Hela, HCT-116, and MCF-7, respectively. The in silico mechanistic study revealed the inhibition of HDAC-6 through the binding of the unique zinc finger ubiquitin-binding domain (HDAC6 Zf-UBD). The docking results showed a specific binding pattern that emphasized the crucial role of the quinoxaline ring and its substituents. The newly developed derivatives were evaluated for antitumor effects against four cancer cell lines PC-3, HeLa, HCT-116, and MCF-7. This research led to the identification of a quinoxaline-based scaffold exhibiting broad-spectrum antiproliferative activity and a distinct mechanism involving binding to HDAC6 Zf-UBD. The findings highlight its potential for further optimization and preclinical studies to support future anticancer drug development. Full article

(This article belongs to the Special Issue Molecular Docking in Drug Discovery, 2nd Edition)

16 pages, 1211 KiB

Open AccessArticle

Exploring the Chemical Composition and Antimicrobial Activity of Extracts from the Roots and Aboveground Parts of Limonium gmelini

by Dariya Kassymova, Francesco Cairone, Donatella Ambroselli, Rosa Lanzetta, Bruno Casciaro, Aizhan Zhussupova, Deborah Quaglio, Angela Casillo, Galiya E. Zhusupova, Maria Michela Corsaro, Bruno Botta, Silvia Cammarone, Maria Luisa Mangoni, Cinzia Ingallina and Francesca Ghirga

Molecules 2025, 30(14), 3024; https://doi.org/10.3390/molecules30143024 - 18 Jul 2025

Limonium gmelini (Willd.) Kuntze, a plant widely used in traditional medicine, has garnered increasing attention for its diverse pharmacological activities, including anti-inflammatory, hepatoprotective, antioxidant, and antimicrobial effects. This study aimed to explore the chemical composition and biological activities of polysaccharides and [...] Read more.

Limonium gmelini (Willd.) Kuntze, a plant widely used in traditional medicine, has garnered increasing attention for its diverse pharmacological activities, including anti-inflammatory, hepatoprotective, antioxidant, and antimicrobial effects. This study aimed to explore the chemical composition and biological activities of polysaccharides and polyphenolic compounds extracted from both the roots and aboveground parts of Limonium gmelini. Several methods of extraction, including ultrasound-assisted extraction (UAE), conventional maceration (CM), and supercritical fluid extraction (SFE), were employed to obtain bioactive fractions. Chemical profiling, primarily represented by monosaccharides and polyphenolic compounds, was characterized and analyzed using proton nuclear magnetic resonance spectroscopy (¹H-NMR) and gas chromatography-mass spectrometry (GC-MS) techniques. While polyphenol-rich fractions exhibited significant antibacterial activity, particularly against Staphylococcus epidermidis, polysaccharide-rich aqueous fractions showed minimal antibacterial activity. Among the methods, CM and UAE yielded higher polyphenol content, whereas SFE provided more selective extractions. Notably, methanolic SPE fractions derived from the roots were especially enriched in active polyphenols such as gallic acid, myricetin, and naringenin, and they exhibited the highest antibacterial activity against Staphylococcus epidermidis. In contrast, extracts from the aboveground parts showed more moderate activity and a partially different chemical profile. These findings underscore the importance of plant part selection and support the targeted use of root-derived polyphenol-enriched fractions from L. gmelini as promising candidates for the development of natural antibacterial agents. Further investigation is needed to isolate and validate the most active constituents for potential therapeutic applications. Full article

(This article belongs to the Special Issue Bioactive Compounds from Roots, Stems, Leaves, Flowers, Fruits, and Seeds: 2nd Edition)

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20 pages, 2293 KiB

Open AccessReview

Nitrate–Nitrite Interplay in the Nitrogen Biocycle

by Biplab K. Maiti, Isabel Moura and José J. G. Moura

Molecules 2025, 30(14), 3023; https://doi.org/10.3390/molecules30143023 - 18 Jul 2025

The nitrogen cycle (N-cycle) is a cornerstone of global biogeochemistry, regulating nitrogen availability and affecting atmospheric chemistry, agricultural productivity, and ecological balance. Central to this cycle is the reversible interplay between nitrate (NO₃⁻) and nitrite (NO₂⁻), mediated [...] Read more.

The nitrogen cycle (N-cycle) is a cornerstone of global biogeochemistry, regulating nitrogen availability and affecting atmospheric chemistry, agricultural productivity, and ecological balance. Central to this cycle is the reversible interplay between nitrate (NO₃⁻) and nitrite (NO₂⁻), mediated by molybdenum-dependent enzymes—Nitrate reductases (NARs) and Nitrite oxidoreductases (NXRs). Despite catalyzing opposite reactions, these enzymes exhibit remarkable structural and mechanistic similarities. This review aims to elucidate the molecular underpinnings of nitrate reduction and nitrite oxidation by dissecting their enzymatic architectures, redox mechanisms, and evolutionary relationships. By focusing on recent structural, spectroscopic, and thermodynamic data, we explore how these two enzyme families represent “two sides of the same coin” in microbial nitrogen metabolism. Special emphasis is placed on the role of oxygen atom transfer (OAT) as a unifying mechanistic principle, the influence of environmental redox conditions, and the emerging evidence of bidirectional catalytic potential. Understanding this dynamic enzymatic interconversion provides insight into the flexibility and resilience of nitrogen-transforming pathways, with implications for environmental management, biotechnology, and synthetic biology. Full article

22 pages, 8519 KiB

Open AccessArticle

RNA-Seq Analysis of MCF-7 Breast Cancer Cells Treated with Methyl Gallate Isolated from the Rhizomes of Nymphaea Odorata L. Shows Upregulation of Apoptosis, Autophagy, and Unfolded Protein Canonical Pathways

by Nishikant A. Raut, Pinal N. Kanabar, Mark Maienschein-Cline, Nina S. Los, Zarema Arbieva, Temitope O. Lawal, Shitalben Patel and Gail B. Mahady

Molecules 2025, 30(14), 3022; https://doi.org/10.3390/molecules30143022 - 18 Jul 2025

The effects of a methanol extract of Nymphaea odorata (MeNO) rhizomes, its fractions and the active compound (methyl gallate, MeG) were investigated in estrogen receptor-positive (ER+) breast cancer cell lines MCF-7 and T47-D:A18, as well as ER-negative line SKBr3. Cell viability and cytotoxicity [...] Read more.

The effects of a methanol extract of Nymphaea odorata (MeNO) rhizomes, its fractions and the active compound (methyl gallate, MeG) were investigated in estrogen receptor-positive (ER+) breast cancer cell lines MCF-7 and T47-D:A18, as well as ER-negative line SKBr3. Cell viability and cytotoxicity were determined using CellTiter-Glo^® 2.0 assays at concentrations ranging from 1 to 100 μg/mL. Caspase activity and apoptosis were determined using Caspase-Glo^® 3/7, Caspase-Glo^® 8, and ApoTox-Glo™ triplex assays, as well as qPCR. Total RNA was isolated from MCF-7 cells treated with MeG. RNA-seq libraries were prepared using a Universal Plus mRNASeq kit, and sequencing was performed on a NovaSeq 6000. MeNO inhibited the growth of MCF-7 cells with an IC₅₀ of 14.1 μg/mL, as well as T47-D:A18 (IC₅₀ of 25.6 μg/mL) and SKBr3 cells (IC₅₀ of 35.5 μg/mL). Bioassay-guided fractionation of MeNO in MCF-7 cells identified the active fraction containing one compound, namely methyl gallate (MeG). MeG had an IC₅₀ of 8.6 μg/mL in MCF-7 cells. Transcriptomic analysis of MeG-treated MCF-7 cells showed differential expression of 10,634 genes, with 5643 upregulated and 4991 downregulated (FDR < 0.05). Ingenuity pathway analysis revealed the involvement of 43 canonical pathways, with the top upregulated pathways including apoptosis, autophagy, and the unfolded protein response pathways. Full article

(This article belongs to the Special Issue Isolation, Analysis, and Biological Activities of Secondary Metabolites Derived from Plants)

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16 pages, 4479 KiB

Open AccessArticle

Photophysical Properties of 1,3-Diphenylisobenzofuran as a Sensitizer and Its Reaction with O₂

by Ștefan Stan, João P. Prates Ramalho, Alexandru Holca and Vasile Chiș

Molecules 2025, 30(14), 3021; https://doi.org/10.3390/molecules30143021 - 18 Jul 2025

1,3-Diphenylisobenzofuran (DPBF) is a widely used fluorescent probe for singlet oxygen (¹O₂) detection in photodynamic applications. In this work, we present an integrated experimental and computational analysis to describe its spectroscopic, photophysical, and reactive properties in ethanol, DMSO, and [...] Read more.

1,3-Diphenylisobenzofuran (DPBF) is a widely used fluorescent probe for singlet oxygen (¹O₂) detection in photodynamic applications. In this work, we present an integrated experimental and computational analysis to describe its spectroscopic, photophysical, and reactive properties in ethanol, DMSO, and DMF. UV-Vis and fluorescence measurements across a wide concentration range show well-resolved S₀ → S₁ electronic transition of a π → π* nature with small red shifts in polar aprotic solvents. Fluorescence lifetimes increase slightly with solvent polarity, showing stabilization of the excited state. The 2D PES and Boltzmann populations analysis indicate two co-existing conformers (C_s and C₂), with C_s being slightly more stable at room temperature. TD-DFT calculations have been performed using several density functionals and the 6-311+G(2d,p) basis set to calculate absorption/emission wavelengths, oscillator strengths, transition dipole moments, and radiative lifetimes. Overall, cam-B3LYP and ωB97X-D provided the best agreement with experiments for the photophysical data across all solvents. The photophysical behavior of DPBF upon interaction with ¹O₂ can be explained by a small-barrier, two-step reaction pathway that goes through a zwitterionic intermediate, resulting in the formation of 2,5-endoperoxide. This work explains the photophysical properties and reactivity of DPBF, therefore providing a solid basis for future studies involving singlet oxygen. Full article

(This article belongs to the Special Issue Quantum Chemical Calculations of Molecular Reaction Processes, 2nd Edition)

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33 pages, 2362 KiB

Open AccessReview

Ferroptosis and Metabolic Dysregulation: Emerging Chemical Targets in Cancer and Infection

by Marta Pawłowska, Jarosław Nuszkiewicz, Dorian Julian Jarek and Alina Woźniak

Molecules 2025, 30(14), 3020; https://doi.org/10.3390/molecules30143020 - 18 Jul 2025

The distinctive nature of ferroptosis is that it is induced chemically and signifies a regulated cell death dependent on iron-dependent lipid peroxidation. The mechanism of ferroptosis involves oxidative damage to the membrane lipids. It differs from apoptosis and necroptosis, triggering metabolic changes in [...] Read more.

The distinctive nature of ferroptosis is that it is induced chemically and signifies a regulated cell death dependent on iron-dependent lipid peroxidation. The mechanism of ferroptosis involves oxidative damage to the membrane lipids. It differs from apoptosis and necroptosis, triggering metabolic changes in the iron-lipid homeostasis and antioxidant defense, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4). Herein, the molecular mechanisms of ferroptosis and its role in the tumorigenesis process and infection-related diseases are presented. It also discusses metabolic reprogramming as a factor that modifies the levels of cell-sensitizing polyunsaturated fatty acids (PUFAs), iron dysregulation, and oxidative stress in aggressive cancers and inflammatory diseases such as sepsis, tuberculosis, and COVID-19. Particular attention is given to chemical modulators of ferroptosis, including synthetic inducers and inhibitors, as well as bioactive natural compounds. Our focus is on the significance of analytical tools, such as lipidomics and metabolomics, in understanding the phenomenon of ferroptosis. Finally, we explore novel therapeutic approaches targeting ferroptosis in cancer and infectious diseases, while navigating both the opportunities and challenges in drug development. The review then draws on chemical biology and disease pathology to propose promising areas of study for ferroptosis-related therapies. Full article

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25 pages, 4365 KiB

Open AccessReview

Advances in α-Arylation of Carbonyl Compounds: Diaryliodonium Salts as Arylating Agents

by Xiao-Wei Chen, Jia-Le Chen, Ling-Hui Zhang, Huhu Zhang, Xiaojun Chen and Xiaohui Fan

Molecules 2025, 30(14), 3019; https://doi.org/10.3390/molecules30143019 - 18 Jul 2025

Diaryliodonium salts are an important part of hypervalent iodine chemistry, owing to their highly electrophilic character, non-toxicity, and air and moisture stability, have been identified as an important arylating agent. It has been widely applied in the synthesis of natural products, drugs, and [...] Read more.

Diaryliodonium salts are an important part of hypervalent iodine chemistry, owing to their highly electrophilic character, non-toxicity, and air and moisture stability, have been identified as an important arylating agent. It has been widely applied in the synthesis of natural products, drugs, and bioactive molecules bearing active α-arylation carbonyl units. Within the domain of α-arylation of carbonyl compounds using diaryliodonium salts, there is a notable absence in the literature of a comprehensive compilation dedicated to exclusive arylation processes involving these compounds. In this review, we focus on the overview of the recent advancements in utilizing diaryliodonium salts for α-arylation reactions, encompassing both racemic and asymmetric approaches to various carbonyl compounds including ketones, esters, enolates, and amides. Furthermore, we discuss the unique advantages and inherent limitations of diaryliodonium salts as arylating agents, as well as the underexplored application potentials that warrant further investigation in this rapidly evolving field. Full article

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29 pages, 11224 KiB

Open AccessReview

Potential of Boronic Acid Derivatization and Activity in Agrochemical Discovery

by Liangshuo Ji, Jianxin Wu, Yachen Zuo, Wenqiang Gao, Jiyao Feng and Zhenhua Zhang

Molecules 2025, 30(14), 3018; https://doi.org/10.3390/molecules30143018 - 18 Jul 2025

Since the approval of Bortezomib (Velcade^®) by the U.S. Food and Drug Administration (FDA) in 2003, boron-containing drugs have successfully entered the global market, spanning therapeutic areas such as anticancer, antibacterial, and antifungal agents. Meanwhile, boron is an essential trace element [...] Read more.

Since the approval of Bortezomib (Velcade^®) by the U.S. Food and Drug Administration (FDA) in 2003, boron-containing drugs have successfully entered the global market, spanning therapeutic areas such as anticancer, antibacterial, and antifungal agents. Meanwhile, boron is an essential trace element for plant growth, and boronic acid has been widely used as plant resistance inducers and growth promoters. In 2024, the Fungicide Resistance Action Committee (FRAC) introduced benzoxaboroles as a new category of fungicides, which fully demonstrates the significant application potential of boron-containing compounds (BCCs) in the field of agricultural fungicides. Recently, studies on BCCs in agriculture have emerged continuously. Compared with the systematic reviews in the pharmaceutical field, those focusing on BCCs in agriculture remain absent. This review systematically collates BCCs with reported biological activities from the literature over the past 20 years, from the perspective of boron-containing building blocks. It mainly focuses on the potential of boronic acid derivatization and its activities in agrochemicals. Additionally, it covers the applications of boron-containing building blocks in pharmaceuticals, including their action mechanisms. Full article

(This article belongs to the Section Organic Chemistry)

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10 pages, 885 KiB

Open AccessArticle

Three New Physalins from Physalis Alkekengi L. var. franchetii (Mast.) Makino

by Ji Zhao, Xiang-Rong Zhang, You Wu, Ying-Li Liu, Yan-Feng Liang and Yang Teng

Molecules 2025, 30(14), 3017; https://doi.org/10.3390/molecules30143017 - 18 Jul 2025

Physalis Alkekengi L. var. franchetii (Mast.) Makino (PAF), which is used in both food and medicine, has a long history of about 1800 years of application in China. There are many active constituents in the calyx of PAF. Physalins and physalins with a [...] Read more.

Physalis Alkekengi L. var. franchetii (Mast.) Makino (PAF), which is used in both food and medicine, has a long history of about 1800 years of application in China. There are many active constituents in the calyx of PAF. Physalins and physalins with a single oxygen bridge are the unique components of the PAF calyx. Physalins with multiple biological activities, including anticancer activity, antimicrobial activity, anti-inflammatory activity, etc., have been found. As such, physalins deserve to be studied further. In this study, we aimed to extract, separate, and identify the effective components of physalins from the calyx of PAF and investigate ability to inhibit the proliferation of tumor cell lines. Three new physalins, physalin VIII (1), 3α-hydroxy-2,3,25,27-tetrahydro-4,7-didehydro-7-deoxyneophysalin A (2), and physalin IX (3), along with three known compounds, physalin L (4), physalin D (5), and alkekengilin A (6) were isolated from PAF calyxes. Physalin D was superior to the positive control drug cisplatin in inhibiting the proliferation of five tumor cell lines. The physalin compounds exhibited potential antitumor activity, being deemed worthy of further research in the fields of antitumor drug development and the application in health foods. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 5939 KiB

Open AccessArticle

Mechanistic Insights into the Hot-Spot Formation and Pyrolysis of LLM-105 with Different Void Defects: A ReaxFF Molecular Dynamics Study

by Mengyun Mei, Zijian Sun, Lixin Ye and Weihua Zhu

Molecules 2025, 30(14), 3016; https://doi.org/10.3390/molecules30143016 - 18 Jul 2025

To investigate the influences of void defects of different sizes, molecular dynamics combined with ReaxFF-lg reactive force field was used to study the hot-spot formation mechanism and thermal decomposition behavior of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) crystals with different void defects at 2500 K. The results [...] Read more.

To investigate the influences of void defects of different sizes, molecular dynamics combined with ReaxFF-lg reactive force field was used to study the hot-spot formation mechanism and thermal decomposition behavior of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) crystals with different void defects at 2500 K. The results indicate that larger void defects are more conducive to the formation of hot-spots. The consistency of the trends in time evolution of the potential energy, species numbers, and small molecules amounts between the ideal and void-containing LLM-105 crystals demonstrates that the presence of the void defect does not alter the decomposition mechanism of the LLM-105 molecule. An increase in the size of the void defect significantly increases the degree of diffusion of the C, H, O, and N atoms in the crystals, which affects the effective collisions between the atoms and thus alters the occurrence frequency of relevant reactions and the production of relevant products. Full article

(This article belongs to the Section Physical Chemistry)

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21 pages, 2186 KiB

Open AccessArticle

Impact of Interactions Between Zn(II) and Selenites in an Aquatic Environment on the Accumulation of Se and Zn in a Fungal Cell

by Małgorzata Kałucka, Piotr Podsadni, Agnieszka Szczepańska, Eliza Malinowska, Anna Błażewicz and Jadwiga Turło

Molecules 2025, 30(14), 3015; https://doi.org/10.3390/molecules30143015 - 18 Jul 2025

Our attempts to obtain a new mushroom-derived immunostimulatory preparation containing organically bound selenium and zinc have focused on the interactions between selenites and zinc(II) in liquid culture media and their effects on transport into the mushroom cell. Previously, we found that, even if [...] Read more.

Our attempts to obtain a new mushroom-derived immunostimulatory preparation containing organically bound selenium and zinc have focused on the interactions between selenites and zinc(II) in liquid culture media and their effects on transport into the mushroom cell. Previously, we found that, even if Zn²⁺ and SeO₃²⁻ concentrations in the liquid medium are not high enough to precipitate ZnSeO₃, the accumulation of selenium in the presence of zinc, and zinc in the presence of selenites, significantly dropped. This effect was more dependent on the molar ratio of ions in the medium than on the concentration values. We hypothesized that the formation of zinc–selenite soluble complexes with charges depending on the ion concentration ratio in the aquatic environment affects the first stage of ion transport into the fungal cell—biosorption. To verify this, we found the zinc–selenite molar ratio at which the complexes of the highest stability are formed, examined the influence of the molar ratio of ions in the medium on the concentration of Zn and Se in the mushroom cell wall, and investigated the correlation between the concentration of selenites not bound in complex compounds and the Se concentration in the cell wall. The results indicate that the molar fraction of Zn(II) in a liquid medium in the range of 0.5–0.6 promotes the formation of the most stable complexes. At the same time, it significantly reduces the percentage of free selenites in the medium and most strongly inhibits the biosorption process of both zinc and selenium. Full article

(This article belongs to the Special Issue Plant-Based Food Science: Chemical Composition and Biological Activity)

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21 pages, 2231 KiB

Open AccessArticle

A Quantitative Model of Chemotherapeutic Drug Sensitivity as a Function of P-Glycoprotein Expression

by Cara M. Robertus, Nisha Kannan and David Putnam

Molecules 2025, 30(14), 3014; https://doi.org/10.3390/molecules30143014 - 18 Jul 2025

(1) Background: Overexpression of P-glycoprotein (P-gp) is one mediator of multidrug resistance in cancer. While many studies demonstrate the efficacy of modulating P-glycoprotein expression to increase drug response in cancer cells, the nature of the mathematical relationship between drug sensitivity and P-glycoprotein surface [...] Read more.

(1) Background: Overexpression of P-glycoprotein (P-gp) is one mediator of multidrug resistance in cancer. While many studies demonstrate the efficacy of modulating P-glycoprotein expression to increase drug response in cancer cells, the nature of the mathematical relationship between drug sensitivity and P-glycoprotein surface density is not yet characterized. (2) Methods: In this study, we employ siRNA to modulate P-gp expression in two model cell lines and evaluate their steady-state response to three common chemotherapeutics in vitro. Additionally, we model the kinetics of calcein-AM, a P-gp substrate, as a function of P-gp expression. (3) Results: For both cell lines, a robust linear relationship governs chemotherapeutic sensitivity as a function of P-gp expression, demonstrating that characterization of P-gp surface density is a strong indicator of drug response in drug-resistant cells. Furthermore, calcein accumulation and initial influx rate exhibit first-order kinetics with respect to P-gp density, further elucidating the nature of substrate interactions with P-gp-overexpressing cells. When transport kinetics are evaluated using a Michaelis–Menten model, V_max varies with P-gp density according to a first-order relationship. (4) Conclusions: These results establish the mathematical relationships between chemotherapeutic response and substrate influx as a function of P-gp expression and suggest that rational changes in P-gp expression could be used as a predictive measure of drug sensitivity in model cell lines. Full article

(This article belongs to the Special Issue New Therapeutic Tools against MDR Tumors: Discovery, Synthesis and Evaluation of Bioactive Compounds)

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19 pages, 3119 KiB

Open AccessArticle

Aquathermolytic Upgrading of Zarafshanian Extra Heavy Oil Using Ammonium Alum

by Amirjon Ali Akhunov, Firdavs Aliev, Nurali Mukhamadiev, Oscar Facknwie Kahwir, Alexey Dengaev, Mohammed Yasin Majeed, Mustafa Esmaeel, Abdulvahhab Al-Qaz, Oybek Mirzaev and Alexey Vakhin

Molecules 2025, 30(14), 3013; https://doi.org/10.3390/molecules30143013 - 18 Jul 2025

The growing global demand for energy necessitates the efficient utilization of unconventional petroleum resources, particularly heavy oil reserves. However, extracting, transporting, and processing these resources remain challenging due to their low mobility, low API gravity, and significant concentrations of resins, asphaltenes, heteroatoms, and [...] Read more.

The growing global demand for energy necessitates the efficient utilization of unconventional petroleum resources, particularly heavy oil reserves. However, extracting, transporting, and processing these resources remain challenging due to their low mobility, low API gravity, and significant concentrations of resins, asphaltenes, heteroatoms, and metals. In recent years, various in situ upgrading techniques have been explored to enhance heavy oil quality, with catalytic aquathermolysis emerging as a promising approach. The effectiveness of this process largely depends on the development of cost-effective, environmentally friendly catalysts. This study investigates the upgrading performance of water-soluble ammonium alum, (NH₄)Al(SO₄)₂·12H₂O, for an extra-heavy oil sample from the Zarafshan Depression, located along the Tajikistan–Uzbekistan border. Comprehensive analyses demonstrate that the catalyst facilitates the breakdown of heavy oil components, particularly resins and asphaltenes, into lighter fractions. As a result, oil viscosity was significantly reduced by 94%, while sulfur content decreased from 896 ppm to 312 ppm. Furthermore, thermogravimetric (TG-DTG) analysis, coupled with Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD), revealed that the thermal decomposition of ammonium alum produces catalytically active Al₂O₃ nanoparticles. These findings suggest that ammonium alum is a highly effective water-soluble pre-catalyst for hydrothermal upgrading, offering a viable and sustainable solution for the development of extra-heavy oil fields. Full article

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40 pages, 3563 KiB

Open AccessReview

Use of Glucose Obtained from Biomass Waste for the Synthesis of Gluconic and Glucaric Acids: Their Production, Application, and Future Prospects

by Mariya P. Shcherbakova-Sandu, Eugene P. Meshcheryakov, Semyon A. Gulevich, Ajay K. Kushwaha, Ritunesh Kumar, Akshay K. Sonwane, Sonali Samal and Irina A. Kurzina

Molecules 2025, 30(14), 3012; https://doi.org/10.3390/molecules30143012 - 18 Jul 2025

The demand for biomass has been growing in recent years for several reasons, related to environmental, economic, and social trends. In the context of global climate changes and the depletion of natural resources, the recycling of plant biomass waste is a promising strategy [...] Read more.

The demand for biomass has been growing in recent years for several reasons, related to environmental, economic, and social trends. In the context of global climate changes and the depletion of natural resources, the recycling of plant biomass waste is a promising strategy for sustainable development that contributes to minimizing waste, improving resource efficiency, and achieving the goal of creating a circular economy. One of the highly demanded products of agricultural waste recycling is glucose. Glucose is an important organic substrate that allows a number of value-added products to be obtained. In this review, we focused on the commercially significant products of glucose oxidation: gluconic and glucaric acids. This review summarized the latest available data on the scope of the application of each product as well as the methods of their production. The capabilities and limitations of currently used methods of synthesis were highlighted. Full article

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19 pages, 1058 KiB

Open AccessArticle

A Brand-New Metal Complex Catalyst-Free Approach to the Synthesis of 2,8-Dimethylimidazo[1,2-b]pyridazine-6-Carboxylic Acid—A Key Intermediate in Risdiplam Manufacturing Process

by Georgiy Korenev, Alexey A. Gutenev, Fyodor V. Antipin, Vladimir V. Chernyshov, Maria P. Korobkina, Maxim B. Nawrozkij and Roman A. Ivanov

Molecules 2025, 30(14), 3011; https://doi.org/10.3390/molecules30143011 - 18 Jul 2025

In this study, we report for the first time a brand-new protocol for the multigram-scale synthesis of 5-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic and 2,8-dimethylimidazo[1,2-b]pyridazine-6-carboxylic acids, without the utilization of metal-complex catalysts. The developed technology for the production of the aforementioned acids is of great importance [...] Read more.

In this study, we report for the first time a brand-new protocol for the multigram-scale synthesis of 5-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic and 2,8-dimethylimidazo[1,2-b]pyridazine-6-carboxylic acids, without the utilization of metal-complex catalysts. The developed technology for the production of the aforementioned acids is of great importance for two reasons. Firstly, these acids serve as intermediates in the synthesis of risdiplam, the first small-molecule drug approved for the treatment of spinal muscular atrophy. Secondly, they themselves are valuable building blocks right from a broader medicinal chemistry perspective. The synthesis of risdiplam was carried out using a modified synthetic protocol, utilizing the acids indicated above as the key intermediates. The protocols presented in this study enable the production of target compounds with high purity and an acceptable yield. Full article

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2 pages, 143 KiB

Open AccessEditorial

Bridging Between Japan-Originated Inorganic Chemistry Theories and the Latest DFT Calculations

by Takashiro Akitsu

Molecules 2025, 30(14), 3010; https://doi.org/10.3390/molecules30143010 - 18 Jul 2025

There are two concepts that were discovered by Japanese researchers that appear in most inorganic chemistry textbooks: the spectrochemical series [...] Full article

(This article belongs to the Special Issue Inorganic Chemistry in Asia)

10 pages, 715 KiB

Open AccessPerspective

The Role of Trifluoromethyl and Trifluoromethoxy Groups in Medicinal Chemistry: Implications for Drug Design

by Manuel Novás and Maria J. Matos

Molecules 2025, 30(14), 3009; https://doi.org/10.3390/molecules30143009 - 18 Jul 2025

One of the key strategies in drug design involves modifying molecular scaffolds with specific chemical groups, or side chains, to enhance biological and physicochemical properties. These modifications can strengthen interactions with biological targets or improve pharmacokinetic and physicochemical characteristics, factors that are critical [...] Read more.

One of the key strategies in drug design involves modifying molecular scaffolds with specific chemical groups, or side chains, to enhance biological and physicochemical properties. These modifications can strengthen interactions with biological targets or improve pharmacokinetic and physicochemical characteristics, factors that are critical in transforming a compound into a viable drug candidate. In this overview, we focus on the presence of trifluoromethyl and trifluoromethoxy groups on different molecules, highlighting their relevance and impact in medicinal chemistry. The discussion and future perspectives in the field are based on a comprehensive review of current literature, with data sourced mainly from SciFinder and PubMed. Full article

(This article belongs to the Section Medicinal Chemistry)

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