Frontiers in Chemistry最新文献

{"title":"Antibody-drug conjugates for infectious and neglected tropical diseases: chemical design principles, target biology, and translational challenges.","authors":"Desigan Reddy, Vineet Jeena, Tshephiso R Papo, Emmanuel C Ohaekenyem","doi":"10.3389/fchem.2026.1793193","DOIUrl":"https://doi.org/10.3389/fchem.2026.1793193","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are established precision treatments in oncology. Nevertheless, their application to infectious diseases and neglected tropical diseases (NTDs) is still an emerging field. In contrast to cancer cells, pathogens exhibit dynamic surface features and distinct intracellular environments, necessitating a complete redesign of the ADC architecture. This review combines chemical concepts and biological insights to outline a \"pathogen-centric\" framework for bacterial, viral, and parasite illnesses. We analyze target selection across various diseases, emphasizing structural accessibility and antigen stability as critical factors. A comprehensive evaluation of ADC chemical architecture is provided, focusing on linkers that respond to pathogen-specific enzymatic or environmental triggers, alongside a range of non-cytotoxic payloads, notably redox-active metallo-drugs designed to overcome antimicrobial resistance. We rigorously analyze the shift from empirical screening to AI-enhanced and structurally-informed design processes. Lastly, we look at the particular translation concerns in this field, such as the Payload Paradox and the complications that come with internalization. We discuss also sustainable biomanufacturing methods that will ensure equitable and fair access to the products. This study offers a chemistry-based framework that outlines the essential ideas required for the advancement of antibody-drug conjugates (ADCs) as targeted anti-infectives for major global infections.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1793193"},"PeriodicalIF":4.2,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-organic frameworks-mediated reactive oxygen species modulation in the tumor microenvironment of digestive system malignancies: latest advances.","authors":"Wei Liu, Chengxin Liu, Meng Wu, Siwen Liu","doi":"10.3389/fchem.2026.1809650","DOIUrl":"https://doi.org/10.3389/fchem.2026.1809650","url":null,"abstract":"<p><p>Digestive system malignancies, such as gastric cancer (GC), colorectal cancer (CRC), and hepatocellular carcinoma (HCC), have become a major global challenge in cancer therapy. These tumors are characterized by high morbidity, strong metastatic potential, and significant chemoresistance, thus posing a severe threat to human digestive health. One of the primary mechanisms underlying the malignant progression of tumors and the development of drug-resistant phenotypes is the imbalance of redox homeostasis in the tumor microenvironment (TME). Its dysregulation is strongly associated with the increased proliferation and invasive potential of tumor cells. As key regulatory molecules in the redox network of the TME, reactive oxygen species (ROS) render precise modulation of their levels a promising strategy for cancer therapy. This approach can not only effectively induce programmed cell death in tumor cells but also reverse the immunosuppressive state of the TME, thus offering novel therapeutic targets for anti-tumor treatment. Metal-organic frameworks (MOFs) are closely associated with metal-based nanomaterials, acting as their excellent precursors and enabling precise modulation of their structures and properties through hybridization. The demand for the precise regulation of ROS in the TME of digestive system malignancies is perfectly met by MOFs, which have emerged as a highly promising nanoplatform for this research field. MOFs have unique advantages such as precisely designable architectures, abundant metallic catalytic active sites, TME-responsive degradation, and high drug loading capacity. This review elucidates the mechanisms underlying MOF-mediated ROS modulation in the TME and highlights its applications in various digestive system malignancies.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1809650"},"PeriodicalIF":4.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147813107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthraquinone-based turn-on fluorescence probe for selective and sensitive detection of Cu²⁺ ions.","authors":"Jiang-Song Jia, Hong-Lei Li, Yi-Fan Xu, Wen-Ming Zhao, Jun Sun","doi":"10.3389/fchem.2026.1761329","DOIUrl":"https://doi.org/10.3389/fchem.2026.1761329","url":null,"abstract":"<p><strong>Introduction: </strong>A novel anthraquinone-hydrazone fluorescent probe (AFSA) was designed and synthesized for the selective and sensitive detection of Cu²⁺ ions, which is of great significance for environmental heavy metal monitoring.</p><p><strong>Methods: </strong>The sensing performance of AFSA was systematically investigated in an EtOH/H₂O (5:1, V/V) binary solution system. Its molecular structure was characterized using multiple spectroscopic techniques, and theoretical spectral properties were further calculated via the GaussView 9.0 quantum chemical program. The binding stoichiometry between AFSA and Cu²⁺ was determined using Job's continuous variation method.</p><p><strong>Results: </strong>AFSA exhibited a distinct turn-on fluorescence response toward Cu²⁺, with a detection limit of 0.86 μM at 766 nm and a response time of less than 1 min. The fluorescence emission remained stable over a wide pH range of 5.0-11.0. Selectivity assays demonstrated negligible interference from common coexisting metal ions, including Al³⁺, Ba²⁺, Ca²⁺, Co²⁺, Hg²⁺, Fe³⁺, K⁺, Mn²⁺, Na⁺, Ni²⁺, Pb²⁺, and Zn²⁺.</p><p><strong>Discussion: </strong>The above results indicate that AFSA is a promising fluorescent probe for Cu²⁺ detection with excellent selectivity, high sensitivity and favorable practical applicability. This work provides a feasible molecular design strategy and a reliable anthraquinone-hydrazone scaffold for the development of high-performance chemosensors toward environmental heavy metal ion monitoring.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1761329"},"PeriodicalIF":4.2,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From waste to resource: circular valorization of spent mushroom substrate into biochar and advanced materials.","authors":"Anagha Sunil, Julia L Shamshina","doi":"10.3389/fchem.2026.1768384","DOIUrl":"https://doi.org/10.3389/fchem.2026.1768384","url":null,"abstract":"<p><p>Spent mushroom substrate (SMS), also known as spent mushroom compost, is the material that is left over after a mushroom crop has been harvested. They typically contain materials like straw, sawdust, or manure, and are rich in mycelium and leftover nutrients. SMS represents a reliable as well as sustainable lignocellulosic feedstock to produce biofuels, hydrochars and value-added products. Evidently, as an abundant waste in the agricultural field, SMS contains high levels of organic matter, making it a promising candidate for conversion into biofuels such as bioethanol, biogas and biochar by different thermochemical and biochemical processes. Hydrothermal carbonization can convert SMS into hydrochars, which can be then used for various applications including but not limited to carbon-based materials and adsorbents. In biofuel production, SMS has shown that it is valuable in fermentation into bioethanol with enzyme action. Due to its lignocellulosic nature, SMS can be further processed into durable materials with exceptional adsorptive properties, can be used in water treatment, pollution control, and soil remediation. Furthermore, the conversion of SMS into biofuels and materials offers a well-round solution for waste management, reducing environmental pollution, promoting circular economies, and supporting the development of renewable energy systems. This review examines the diverse uses of SMS, focusing on its potential as a biochar, biofuel and material precursor, and highlights the technological challenges and opportunities for optimizing the conversion processes.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1768384"},"PeriodicalIF":4.2,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical profiling and multi-target pharmacological evaluation of <i>Symphyotrichum squamatum</i> unveils its potential as a source of antidiabetic and anti-inflammatory agents.","authors":"Mohammed Hassan, Islam Mostafa, Ahmed M Saad, Ahmed S AbdelKhalek, Mahmoud M Elaasser, Zepeng Yin, Mahmoud Sitohy, Mohamed El-Sadek, Omer I Fantoukh, Assem M El-Shazly, Mona Fekry","doi":"10.3389/fchem.2026.1734411","DOIUrl":"https://doi.org/10.3389/fchem.2026.1734411","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to thoroughly profile the phytochemicals and pharmacological properties of <i>Symphyotrichum squamatum's</i> aerial parts to assess its potential as a valuable source of natural therapeutic agents. The research focused on isolating and identifying bioactive compounds and evaluating their antioxidant, cytotoxic, antidiabetic, and anti-inflammatory effects.</p><p><strong>Method: </strong>Chromatographic purification, LC/MS, total flavonoids, total phenolics, molecular docking and different pharmacological activity were used in this study to identify qualitatively and qualitatively the active compounds in extract and its activities.</p><p><strong>Results: </strong>Chromatographic purification of the petroleum ether and ethyl acetate fractions led to the isolation of four compounds: 3α- Friedelinol, Spinasterol, Dioctyl phthalate, and Kaempferol-3,7- diglucopyranoside. Additionally, the LC/MS profile of the hydro-alcoholic extract identified 35 metabolites, indicating a diverse chemical profile rich in fatty acids, phenolic propanoids, and terpenoids. Quantitative assays confirmed the extracts abundance in phenolics (65.9 ± 3.6 mg GAE/g extract) and flavonoids (25.8 ± 1.1 mg QE/g extract), correlating with notable in vitro antioxidant activity, as shown by low SC₅₀ values of 77.00 μg/mL (DPPH) and 66.00 μg/mL (ABTS). The extract exhibited weak cytotoxicity against Hep-G2 and Panc-1 cell lines. Notably, both the extract and the isolated Kaempferol-3,7- diglucopyranoside demonstrated potent, dose-dependent inhibition of key carbohydrate-digesting enzymes, indicating antidiabetic activity. The flavonoid glycoside was particularly effective against α-amylase (IC₅₀ = 24.29 μg/mL). The extract also showed promising anti-inflammatory activity via COX-1 inhibition (IC₅₀ = 137.51 μg/mL). To explain these bioactivities, molecular docking studies were performed, revealing that the essential compounds, namely Kaempferol-3,7-diglucopyranoside and dicaffeoylquinic acids, form stable, high-affinity interactions with the reactive sites of α-amylase, α-glucosidase, and COX enzymes.</p><p><strong>Discussion: </strong>These findings collectively support <i>S. squamatum</i> as a promising candidate for further development in the management of diabetes and inflammation.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1734411"},"PeriodicalIF":4.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfer of structural units through imine exchanges, in solution or without solvent: successive transiminations, stimuli (pH)-modulated covalent switches, and mathematical models.","authors":"Juan Ramirez, Adrian-Mihail Stadler","doi":"10.3389/fchem.2025.1241625","DOIUrl":"https://doi.org/10.3389/fchem.2025.1241625","url":null,"abstract":"<p><p>Transfer of structural units through covalent constitutional (non mechanical) switches based on (bis-)imine/amine exchanges (transiminations), can reversibly be modulated by external stimuli, namely by pH changes through alternate additions of acid and base. This is illustrated in this work, in solution, by means of mono- and dialdehydes derived from pyridine. For example, in the case of a dialdehyde Ald, its reaction with an aromatic amine Am1, produces a first bis-imine Im1. Reaction of bis-imine Im1 with an aliphatic amine Am2 produces the aliphatic bis-imine Im2. Addition of acid regenerates the first bis-imine Im1. Subsequent addition of base produces again the second bis-imine Im2. The aromatic amines Am1 used in this work are aniline-based ones, while the aliphatic ones Am2 are primary alkylamines. Trifluoroacetic acid (TFA) and triethylamine (TEA) are used as pH-triggers (external stimuli) in solution. No metal ions are needed to perform the exchanges. In several cases, an excess of aromatic amine Am1, and further, correlatively, an excess of amine Am2 were used to increase the yields. It is also shown that it is possible to invert the steps and to start with aliphatic amine Am2, to continue with aromatic amine Am1 and acid, then, after appropriate adjustments, with base. (Bis-, tris-)imine/(di)aldehyde exchanges in solution were investigated as well. In addition, in a green chemistry approach, under solvent-free conditions, were performed formation of imines, (bis-)imine/amine exchanges and (bis-)imine/(di)aldehyde exchanges, as well as multistep sequences of successive transiminations. In the solvent-free imine/aldehyde-type sequence of successive exchanges, a monoimine is converted into a tris-imine, the tris-imine, into a bis-imine, which finally generates a new monoimine. In the solvent-free imine/amine-type sequence of transiminations, three monoimines derived from the same aldehyde, are successively generated. The experimental work is complemented with an equilibrium-constants-based, mathematical treatment of exchanges between amines and dialdehyde-based bis-imines at equilibrium, in solution: calculation of the composition at equilibrium, modeling of the pH-adaptive behavior of small dynamic libraries of imines, as well as water-dependent distribution curves. Under particular conditions, a simplified mathematical approach to exchanges (transiminations) can be used, where equilibriums involving di- or monoaldehydes do not appear directly.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"13 ","pages":"1241625"},"PeriodicalIF":4.2,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive modeling and ranking of physicochemicals in <i>Aegle marmelos</i> using topological indices and multi-criteria decision-making techniques.","authors":"Aditya Narayan Bhandari, Jaganathan B","doi":"10.3389/fchem.2026.1740913","DOIUrl":"https://doi.org/10.3389/fchem.2026.1740913","url":null,"abstract":"<p><p><i>Aegle marmelos</i> (Bael Patra) contains diverse bioactive phytochemicals with significant therapeutic potential. However, it is observed that systematic computational methods for their evaluation remain limited. In this study, an integrated framework has been devised which combines quantitative structure-property relationship(QSPR) modelling and multi-criteria decision-making (MCDM) techniques to analyse and rank 15 key phytochemicals. A set of six physicochemical properties, such as molecular weight (MW), topological polar surface area (TPSA), hydrogen bond donor (HBD) and acceptor (HBA) counts, melting point (MP), and rotatable bond count (RBC) were modelled using 16 adriatic topological indices through pairwise multiple linear regression. The statistically robust models with R² ≥ 0.99 were retained. The frequency of the occurrence of descriptors in these models was used to derive objective weights, which were used in VIKOR,SAW and TOPSIS methods for ranking of compounds. The results demonstrate high predictive accuracy, with MW showing the strongest predictability and the inverse sum indeg (ISI) index emerging as the most influential descriptor. The three MCDM methods showed strong agreement, consistently identifying riboflavin, ellagic acid, and kaempferol as the top-ranked compounds. The unified approach, linking regression-based descriptor importance with decision making techniques, provides a robust and scalable approach for compound prioritization. The study possesses potential applications in virtual screening and early-stage drug discovery of plant derived molecules.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1740913"},"PeriodicalIF":4.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QM/MM hybrid simulation of enzyme-Mn synergistic catalysis for quinazolinones: computational determination of activation energy and transition state.","authors":"Haotian Cao","doi":"10.3389/fchem.2026.1792714","DOIUrl":"https://doi.org/10.3389/fchem.2026.1792714","url":null,"abstract":"<p><p>Quinazolinone derivatives are important nitrogen-containing heterocycles widely used in antitumor agents and functional materials, but their conventional synthesis often relies on noble-metal catalysts and inefficient multistep processes with considerable environmental costs. In this study, we developed a QM/MM hybrid simulation and experimental validation framework to investigate the synergistic catalytic mechanism of an enzyme-Mn system for quinazolinone synthesis and to clarify how metal pre-activation and enzymatic microenvironment jointly regulate the reaction pathway and transition-state stability. Density functional theory, QM/MM calculations, and molecular dynamics simulations were integrated to quantify geometric configuration, charge distribution, solvation effects, substrate binding, and transition-state evolution in the catalytic process. The results showed that Mn-assisted enzyme catalysis reduced the activation energy by 36.5% compared with the enzyme-only system, while the predicted transition-state infrared frequencies deviated by less than 8 cm^-1 from experimental measurements and the overall computational error remained below 2.5%. In addition, optimization of Mn charge states substantially improved catalyst cyclability, with an approximately sevenfold enhancement in reuse performance. These findings demonstrate that the synergistic effect between Mn-mediated substrate pre-activation and the enzymatic hydrogen-bond network is the key factor underlying efficient quinazolinone formation, and they provide a reliable theoretical basis for the design of noble-metal-free hybrid catalytic systems for sustainable synthesis.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1792714"},"PeriodicalIF":4.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 Mpro inhibitors from <i>Siphonostegia chinensis</i>: an integrated biophysical and computational study.","authors":"Yingjie Ren, Wei Wang, Dai Zhang, Mingliang Zhang, Hui Zhang, Yali Wu, Feiyan Liu, Liuqing Yang, Pan Wang, Lei Chen, Xiaofei Chen, Jinfa Tang, Xianqing Ren","doi":"10.3389/fchem.2026.1790228","DOIUrl":"https://doi.org/10.3389/fchem.2026.1790228","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic caused by SARS-CoV-2 underscores the urgent need for novel antiviral agents. Preliminary screening indicated that the traditional Chinese medicine <i>Siphonostegia chinensis</i> Benth. (Bei Liu Ji Nu) possesses inhibitory activity against the SARS-CoV-2 main protease (Mpro), a key enzyme for viral replication.</p><p><strong>Methods: </strong>To identify the active constituents responsible for its anti-SARS-CoV-2 activity, we employed an integrated strategy combining bio-layer interferometry (BLI) and ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS).</p><p><strong>Results: </strong>Two phenolic compounds, verbascoside and 3,4-dicaffeoylquinic acid, were successfully fished out and identified from the ethanol extract as the most potent binders to Mpro. The binding affinities (KD) were determined to be 2.149 × 10^-6 M and 2.487 × 10^-5 M, respectively. Subsequent <i>in vitro</i> enzymatic inhibition assays confirmed their inhibitory effects, with IC₅₀ values of 0.076 µM and 0.194 µM, respectively. To elucidate the inhibition mechanism, molecular docking and molecular dynamics simulations were performed, revealing stable binding modes of both compounds within the catalytic pocket of Mpro through key interactions. Preliminary ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions were also conducted to assess their drug-likeness.</p><p><strong>Conclusion: </strong>Our findings demonstrate that verbascoside and 3,4-dicaffeoylquinic acid exhibit high binding affinity and structural stability against SARS-CoV-2 Mpro, highlighting their potential as lead compounds for inhibiting viral replication. Furthermore, the comprehensive strategy established in this study provides a reliable and efficient approach for identifying bioactive components from complex herbal matrices, offering new perspectives and a scientific basis for the development of natural product-derived targeted therapeutics.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1790228"},"PeriodicalIF":4.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of mono- and di-(<i>C</i>-glycopyranosyl-isoxazol(in)yl) derivatives on aromatic scaffolds and their evaluation as anti-adherence agents of <i>Candida albicans</i>.","authors":"Tímea Kaszás, Bence Szakács, Tekla Blága, Kyle Doherty, Rachel Keenan-Dillon, Shauna Reynolds, Kevin Kavanagh, Trinidad Velasco-Torrijos, László Somsák, Marietta Tóth","doi":"10.3389/fchem.2026.1794047","DOIUrl":"https://doi.org/10.3389/fchem.2026.1794047","url":null,"abstract":"<p><p>The yeast <i>Candida albicans</i> is one of the most prevalent fungal pathogens. It induces superficial and systemic infections in immunocompromised patients. The high pathogenicity of <i>Candida</i> species may be related to their adherence to the host tissues. Cell surface glycans are important receptors for <i>C. albicans</i> and warrant the development of anti-adherence ligands that can mimic them and disrupt <i>C. albicans</i>-epithelial cell interactions. A divalent galactoside glycomimetic containing 1,2,3-triazole units was found to be one of the most potent inhibitors of <i>C. albicans</i> adhesion to exfoliated buccal epithelial cells. Based on this lead molecule, herein we report on the synthesis and evaluation of a new series of mono- and divalent glycosides, featuring isophthalamide and benzene scaffolds with <i>C</i>-glycosyl isoxazoline and isoxazole, as well as <i>N</i>-glycosyl 1,2,3-triazole units. The new compounds were obtained by 1,3-dipolar cycloaddition reactions between the above scaffolds functionalized with one or two alkenyl or alkynyl moieties and glycosyl nitrile oxides and glycosyl azides, respectively. The tested deprotected compounds were non-toxic to the <i>C. albicans</i> cells and exhibited significant inhibition of <i>C. albicans</i> adhesion, showing good and moderate inhibition in exclusion and competitive assays, respectively. This study demonstrated the utility of isoxazole/isoxazoline heterocycles to replace 1,2,3-triazoles in aromatic-core glycoconjugates to furnish anti-adhesion molecules equipotent with the lead and also showed that the simple benzene core can serve well in potential anti-adhesives against <i>C. albicans</i>.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"14 ","pages":"1794047"},"PeriodicalIF":4.2,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}