Current topics in medicinal chemistry最新文献

{"title":"Unveiling the Phytopharmacological Potential of Morus alba: Bioactive Constituents, Therapeutic Potential, and Future Prospects.","authors":"Akash Bhati, Navneet Sharma, Bharat Bhusan, Praveen Nasa, Deepika Bhatia, Hitesh Kumar Dewangan","doi":"10.2174/0115680266474686260903044801","DOIUrl":"https://doi.org/10.2174/0115680266474686260903044801","url":null,"abstract":"<p><p>Morus alba L., a member of the Moraceae family, is widely recognised for its medicinal and nutritional importance. Various extracts from Traditional Chinese, Ayurvedic, and Korean medicine systems are widely used, including tree leaves, fruits, root bark, and branches. This review critically summarises the pharmacological potential, phytochemical profile, and emerging therapeutic applications of Morus alba L. based on available preclinical and analytical studies. These activities are attributed to diverse bioactive constituents, including stilbenes, anthocyanins, phenolic acids, alkaloids, and flavonoids. Besides, the plant is important in sericulture and offers possible health advantages as a health supplement, herbal tea, jams, oils, and functional foods. This review compiles and evaluates extraction and analytical techniques used for the identification and characterisation of bioactive compounds from Morus alba. These include HPLC, GC-MS, NMR, ethanol-based extraction, hot water extraction, and advanced proteomic and metabolomic approaches. Chemometric tools, along with HPLC-DAD and UHPLC-ESI-MSn, are widely used for quality assessment and chemical standardisation. Recent studies in emerging areas such as molecular docking, ligand fishing, and nanoparticle-based systems further highlight its potential in drug discovery and delivery. Morus alba-mediated nanoparticles have also demonstrated antimicrobial, antioxidant, and drug delivery potential. This review highlights current evidence, identifies research gaps, and provides future directions for the development of Morus alba-based therapeutic and functional applications.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliability of Machine Learning Approaches Towards the Identification of Novel PI4KIIIβ Inhibitors.","authors":"Priyanka Andola, Prasanna Sagane, Lalitha Guruprasad","doi":"10.2174/0115680266517367261009103151","DOIUrl":"https://doi.org/10.2174/0115680266517367261009103151","url":null,"abstract":"<p><strong>Introduction: </strong>The type III Phosphatidylinositol 4-kinase (PI4KIIIβ) serves as a key host factor that mediates the replication of RNA viruses and is involved in essential membrane trafficking events. The development of PI4KIIIβ-specific inhibitors could give insights into the enzyme's function and contribute to the treatment of viral diseases. However, the molecular features that determine inhibitor activity and selectivity remain unclear.</p><p><strong>Methods: </strong>PI4KIIIβ inhibitors with reported biological activities (pIC50) were systematically analyzed using machine-learning methods. Molecular characterization was performed using RDKit, Chemopy descriptors, and PubChem fingerprints. Multiple classification and regression models were developed and evaluated using 10-fold cross-validation to establish robust structureactivity relationships.</p><p><strong>Results: </strong>It was suggested that the PubChem fingerprint-based linear regression, SMOreg, and GaussianProcesses models were more appropriate for the studied dataset to deliver the best predictive ability, which showed a correlation coefficient value > 0.7 in the 10-fold crossvalidation. PubChemFP389 and PubChemFP572, representing amidine-like fragments or guanidine- related motifs, and the aromatic amine fragment showed a negative correlation with respect to biological activity.</p><p><strong>Discussion: </strong>The study describes predictive models and provides insights into essential structural features in chemical compounds relevant for inhibitory activity, which could assist in the design and optimization of novel PI4KIIIβ inhibitors for antiviral and anticancer applications. A similar approach may be extended to a larger dataset of molecules or to other related drug targets.</p><p><strong>Conclusions: </strong>The findings suggest that excessive basicity and certain polar functionalities may be detrimental to PI4KIIIβ inhibition, providing important insights into the structural features influencing ligand binding and activity.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppressing Liver Cancer via the VEGFR1 Receptor using De novo Ellagic Acid Derivatives and Co-drugs: Comprehensive In silico Biochemistry Research with ADMET, RMSD, Molecular Docking, and Molecular Dynamics Simulations.","authors":"Soykan Agar, Esra Acar, Ozan Aldemir, Erkan Gokoluk, Ghassan Issa, Jane Bogdanov","doi":"10.2174/0115680266507814260929070719","DOIUrl":"https://doi.org/10.2174/0115680266507814260929070719","url":null,"abstract":"<p><strong>Introduction: </strong>Ellagic acid, Formononetin, and Glycitein are bioactive polyphenols possessing anticancer activity via apoptosis, cell cycle inhibition, and oncogenic signaling pathway modulation. In particular, Ellagic acid demonstrated interesting activity towards hepatocellular carcinoma (HCC), with the potential antiangiogenic target being VEGFR1. This study explores fluorinated Ellagic acid derivatives as potential VEGFR1 inhibitors, overcoming disadvantages of Formononetin/Glycitein co-drugs, namely poor ADME properties, hERG liability, and low bioavailability.</p><p><strong>Methods: </strong>Geometry optimization was carried out using DFT with the B3LYP/6-31G(d,p) basis set. Molecular docking with AutoDock Vina was applied in order to assess binding energies and inhibitory constants. Further MD simulation was conducted under physiological conditions using the OPLS 3.0 force field.</p><p><strong>Results: </strong>Ellagic acid established stable hydrogen-bond interactions with VEGFR1. Fluorination improved predicted binding affinity, inhibitory potency, and lipophilicity. Although the co-drugs exhibited stronger binding energies, they showed less favorable predicted ADMET profiles and increased toxicity alerts. All complexes remained highly stable during MD simulations (RMSD <1 Å).</p><p><strong>Discussion: </strong>Prioritization of fluorinated Ellagic acid was conducted according to favorable MM/GBSA binding energy, inhibitory constant, lipophilicity, oral bioavailability, and lack of predicted hERG-related cardiotoxicity. Formononetin and Glycitein demonstrated lower drug-likeness and predicted oral bioavailability and had cardiotoxicity issues.</p><p><strong>Conclusion: </strong>Fluorinated Ellagic acid derivatives could be considered as potential inhibitors of VEGFR1 due to their favorable binding characteristics and structural stability, along with predicted good ADMET properties without QikProp toxicity alerts.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Phenylbutyric Acid: Evans Blue and Ibuprofen as Albumin- Binding Motifs for PSMA-Targeted Radioligand Therapy of Prostate Cancer.","authors":"Cyril Fersing, Johanne Vanney, Jade Torchio, Stephane C Renaud, Lea Rubira","doi":"10.2174/0115680266495475260908114649","DOIUrl":"https://doi.org/10.2174/0115680266495475260908114649","url":null,"abstract":"<p><strong>Introduction: </strong>Radioligand Therapy (RLT) targeting Prostate-Specific Membrane Antigen (PSMA) reshapes the therapeutic landscape of metastatic castration-resistant prostate cancer. However, the rapid systemic clearance of small-molecule radioligands directly affects circulation time and tumor exposure. Reversible albumin binding emerged as a practical strategy to extend circulation and modulate biodistribution. Among drug-derived Albumin-Binding Moieties (ABMs), Evans Blue (EB) and ibuprofen (Ibu) offer distinct approaches to improve pharmacokinetics and the therapeutic index.</p><p><strong>Methods: </strong>This review analyzes the design, synthesis, structure-activity relationships, and evaluation of PSMA radioligands incorporating EB- or Ibu-derived ABMs. Preclinical and clinical literature was examined, with emphasis on translational candidates.</p><p><strong>Results: </strong>EB confers strong albumin binding and markedly prolongs tumor residence, whereas Ibu enables more finely tunable interactions with albumin. The impact of linker, radionuclide, and albumin affinity on biodistribution, dosimetry, and therapeutic efficacy are essential to consider. Available data suggest that albumin binding is a tunable pharmacokinetic parameter rather than a binary property. Clinical experience with EB-PSMA-617 and SibuDAB demonstrates that increasing tumor absorbed dose through prolonged circulation is achievable but may increase irradiation of kidneys, bone marrow, and salivary glands.</p><p><strong>Discussion: </strong>These findings support the hypothesis that moderately strong, tunable albumin binding offers the most favorable therapeutic window. Stereochemical optimization of Ibu-derived ABMs and linker engineering illustrate how subtle structural changes can rebalance tumor uptake, clearance, and safety. Future radiopharmaceutical design will likely rely on iterative structure- pharmacokinetic optimization and dosimetry to define optimal albumin affinity.</p><p><strong>Conclusion: </strong>Overall, ABMs appear to be central tools for the design of next-generation PSMA radioligands and other radiopharmaceuticals.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico and In vitro Investigation of the Antibacterial Potential of Substituted Aminonitriles.","authors":"Gisvaldo Cavalcante Prado Filho, Bianca Araujo Fernandes Veras, Pamela Isabel Japura Huanca, Helivaldo Diogenes da Silva Souza, Savio Benvindo Ferreira","doi":"10.2174/0115680266459999260910044029","DOIUrl":"https://doi.org/10.2174/0115680266459999260910044029","url":null,"abstract":"<p><strong>Introduction: </strong>Aminonitriles are important synthetic intermediates widely used in the development of compounds with potential antibacterial activity. Previous studies have demonstrated antimicrobial activity in some representatives of this chemical class, suggesting that these compounds may exhibit intrinsic antibacterial properties. Considering the growing global concern regarding antimicrobial resistance, the search for new substances capable of combating resistant microorganisms has become increasingly important. Therefore, this study aimed to investigate the in silico and in vitro antibacterial potential of synthetic aminonitriles. The in silico analysis predicted activities related to the treatment of phobic disorders, inhibition of ubiquinol-cytochrome c reductase, and inhibition of membrane permeability. In the in vitro assays, antibacterial activity was identified by the microdilution method, with Minimum Inhibitory Concentrations (MICs) of 512 μg/mL, 128 μg/mL, and 512 μg/mL for HAN-1, HAN-3, and HAN-8 against Enterococcus faecalis, Staphylococcus epidermidis, and Staphylococcus aureus, respectively.</p><p><strong>Materials and methods: </strong>The molecules used in the in silico assays were converted into SMILES format using Discovery Studio software and analyzed using the PASS Online platform to predict their potential biological activities. The in vitro evaluation initially employed the disk diffusion method to assess inhibition halo formation. Subsequently, broth microdilution assays were performed to determine the minimum inhibitory concentrations of the aminonitriles against grampositive strains (Staphylococcus epidermidis ATCC 12228, Staphylococcus aureus ATCC 25923, and Enterococcus faecalis ATCC 29212) and gram-negative strains (Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 25933, and Escherichia coli ATCC 25922).</p><p><strong>Results: </strong>Computational analyses identified the main predicted bioactivities as treatment of phobic disorders, inhibition of ubiquinol-cytochrome-c reductase, and inhibition of membrane permeability. In the in vitro assays, antibacterial activity against S. epidermidis, S. aureus, and E. faecalis was detected using the microdilution technique.</p><p><strong>Discussion: </strong>This study presents a comparative evaluation of the in silico and in vitro antibacterial potential of seven aminonitrile derivatives. Although the in silico analyses suggested potential biological activities, the in vitro assays demonstrated limited antibacterial activity against the tested strains.</p><p><strong>Conclusion: </strong>Some aminonitrile derivatives demonstrated potential biological activities, particularly regarding predicted pharmacological activities and bacteriostatic effects against selected Grampositive bacteria. Therefore, further investigations are necessary to better understand their mechanisms of action and explore their therapeutic potential.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence for Natural Products Discovery and Development.","authors":"Weijin Wang, Zhaoxin Xu, Yugang Lin, Jie Liao","doi":"10.2174/0115680266488712260831171806","DOIUrl":"https://doi.org/10.2174/0115680266488712260831171806","url":null,"abstract":"<p><p>Natural products (NPs) remain a cornerstone of modern drug discovery, offering stereochemical complexity and diverse bioactivities that precisely modulate therapeutic targets, refined through billions of years of evolution. However, their research has long been hindered by inefficient, empirical workflows, high resource consumption, structural complexity, and the \"multicomponent, multi-target\" nature of their mechanisms. The exponential growth of genomic, metabolomic, and spectral data has overwhelmed conventional analytical methods, exposing critical bottlenecks in handling high-dimensional, heterogeneous datasets that exceed human interpretive capacity. Artificial intelligence (AI) is emerging as a transformative paradigm to address these challenges, integrating multi-omics and chemical data to shift NP research from fragmented empiricism toward mechanism-driven, precision-oriented development. By leveraging deep learning architectures- including graph neural networks, Transformers, and diffusion-based generative models-AI enables systematic decoding of NP biosynthesis, automated structure elucidation, rational target identification, knowledge extraction from vast unstructured scientific literature, and de novo molecular design. This review comprehensively surveys recent advances in AI applications across the full NP discovery and development pipeline, encompassing genome mining, structure-based and ligand-based virtual screening, multimodal structural characterization, lead optimization, and biosynthetic pathway engineering. We further examine the emerging roles of protein-centric, molecule- centric, and multimodal foundation models, as well as large language models, in bridging genotype-to-chemotype gaps and unlocking unstructured scientific knowledge. Finally, we discuss critical challenges including data scarcity, representational limitations for complex stereochemistry, physical plausibility in generative models, and the urgent need for experimental validation, while outlining future directions toward autonomous experimentation, closed-loop optimization, and human-AI collaborative discovery.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review of Chalcones in Dual-Targeted Therapeutics for the Treatment of Parkinson's Disease.","authors":"Keerthana Dhinakaran, Amuthalakshmi Sivaperuman, Ramalakshmi Natarajan, Yuvarani Kesavan, Nalini Calambur Nagarajan, Viswas Raja Solomon","doi":"10.2174/0115680266472132260829141305","DOIUrl":"https://doi.org/10.2174/0115680266472132260829141305","url":null,"abstract":"<p><strong>Introduction: </strong>The design of novel therapeutic entities for neurodegenerative diseases, particularly Parkinson's disease, remains a major challenge in medicinal chemistry. Current treatment strategies primarily rely on symptomatic management, often involving levodopa in combination with catechol-O-methyltransferase (COMT) inhibitors to prolong its therapeutic effect. However, these approaches do not adequately address the multifactorial nature of the disease. This study aims to explore the potential of chalcone derivatives as dual-target-directed ligands capable of modulating both COMT and adenosine A₂A receptors for improved therapeutic outcomes in Parkinson's disease.</p><p><strong>Methods: </strong>A comprehensive analysis of chalcone-based scaffolds, particularly those incorporating heterocyclic moieties, was undertaken to evaluate their suitability as multitarget agents. Emphasis was placed on their structural versatility and ability to interact with key biological targets involved in Parkinson's disease pathology.</p><p><strong>Results: </strong>Chalcones exhibit promising pharmacological properties, including the ability to inhibit COMT, thereby reducing levodopa metabolism, and antagonize adenosine A₂A receptors, which play a crucial role in regulating neurotransmission and motor function.</p><p><strong>Discussion: </strong>The incorporation of heterocyclic substituents appears to enhance target affinity and selectivity, likely through improved molecular interactions within the binding site. Furthermore, the observed multitarget activity may confer synergistic therapeutic benefits by concurrently modulating multiple pathological pathways, which is particularly advantageous for the treatment of complex multifactorial diseases.</p><p><strong>Conclusion: </strong>Chalcone derivatives represent a promising class of multitarget compounds for Parkinson's disease management. Their dual inhibitory activity against COMT and A₂A receptors, combined with their structural flexibility, supports their potential for further development as effective neuroprotective agents.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Investigation of the Anti-Atherosclerotic Mechanism of 4',7-di- O-Methylnaringenin from Zingiberaceae Plants.","authors":"Dong-Bin Zhang, Ya-Fei Qin, Huan-Huan Gu, Ru-Tao Xu, Dang-Hui Lu, Jiang-Bo Chen, Dagui Chen, Fu-Sheng Shang, Ke-Wei Zhang","doi":"10.2174/0115680266473984260826100439","DOIUrl":"https://doi.org/10.2174/0115680266473984260826100439","url":null,"abstract":"<p><strong>Introduction: </strong>Atherosclerosis (AS) is a chronic inflammatory disease driven by disordered lipid metabolism and is a major cause of cardiovascular disease. 4',7-Di-Omethylnaringenin (DMNG), a natural flavonoid derived from Zingiberaceae plants, has diverse biological activities, particularly anti-inflammatory and antioxidant effects. This study aimed to investigate the therapeutic effects of DMNG on AS and elucidate its underlying molecular mechanisms using proteomics.</p><p><strong>Methods: </strong>C57BL/6 mice fed a standard diet served as normal controls, whereas ApoE-/- mice fed a high-fat diet (HFD) were used as an AS model. ApoE-/- mice were treated with DMNG (25, 50, or 100 mg/kg/day) for 12 weeks. Body weight, serum lipid profiles, inflammatory cytokines, and oxidative stress markers were measured. Histopathological changes in the aorta were assessed using H&E and Masson's trichrome staining. Proteomic analysis was performed to identify key proteins and pathways, followed by validation using Western blotting.</p><p><strong>Results: </strong>DMNG treatment significantly reduced body weight gain and alleviated aortic intimal hyperplasia, plaque formation, and inflammatory infiltration while increasing collagen deposition. It improved lipid profiles by decreasing serum TC, TG, and LDL-C levels and increasing HDL-C levels. DMNG also reduced the serum levels of pro-inflammatory cytokines (IL-1β, IL- 6, and TNF-α), enhanced antioxidant enzyme activities (SOD and GSH-Px), and decreased MDA levels. Proteomic analysis identified ICAM1 as a protein downregulated by DMNG and implicated the MAPK/NF-κB pathway as the main regulatory axis. Western blotting confirmed that DMNG reduced the levels of ICAM1, p-p65, p-IκB, p-ERK, and p-p38.</p><p><strong>Discussion: </strong>These findings identify ICAM1 as a critical factor through which DMNG exerts its anti-atherosclerotic effects. By suppressing ICAM1 expression and the MAPK/NF-κB signaling pathway, DMNG alleviates vascular inflammation and oxidative stress, two core pathological processes in AS. Given the incomplete efficacy and adverse effects of current lipid-lowering therapies in some patients, DMNG, a natural flavonoid with multi-target activity, may represent a therapeutic candidate for managing AS, particularly its inflammatory components.</p><p><strong>Conclusion: </strong>DMNG ameliorates atherosclerosis by suppressing ICAM1 expression and MAPK/NF-κB signaling.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytotherapeutic Frontiers: A Comprehensive Review of Medicinal Plants as Adjuncts in COVID-19 Management.","authors":"Rabab M Nasser","doi":"10.2174/0115680266471896260828091219","DOIUrl":"https://doi.org/10.2174/0115680266471896260828091219","url":null,"abstract":"<p><p>Unexpected findings emerge when nature encounters pandemic challenges. From mountain slopes, remedies arise shaped by harsh climates. Such conditions foster strong chemical defenses in plants. One such defense disrupts a key virus enzyme, similar to lab-made drugs. Instead of only attacking germs, these substances also calm body reactions gone awry. They can block the spike protein's interaction with human cells while reducing excessive immune signals associated with severe illness. Structural features within these compounds may explain why some are more effective than others. Tiny carriers developed through advanced methods help them reach target sites more effectively. Evidence has accumulated gradually across recent studies. Not every plant compound is equally successful, as effectiveness depends on precise molecular interactions and stability within the body. Delivery may be as important as the compound's origin or structure. Insights come not from individual experiments alone, but from patterns observed across multiple studies. Most importantly, different levels of evidence are distinguished here, ranging from lab experiments and computer forecasts to animal tests and limited human research, with the awareness that digital results often fail in real medical settings unless confirmed through rigorous testing. Rooted in traditional plant knowledge yet guided by modern methods, this study maps a path toward discovering natural remedies while maintaining a critical assessment of whether the reported health benefits are supported by sufficient evidence.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Internal Stimuli-Responsive Nanocarriers for Dermal and Transdermal Drug Delivery: Mechanisms, Materials, and Translational Challenges.","authors":"Lalit Kumar, Ashish Sarkar, Renu Dwivedi, Arijit Chaudhuri, Anju Goyal, Biswajit Dash, Ananya Balaji","doi":"10.2174/0115680266497470260826080219","DOIUrl":"https://doi.org/10.2174/0115680266497470260826080219","url":null,"abstract":"<p><strong>Introduction: </strong>There are several problems with cutaneous or transdermal drug delivery, including suboptimal drug penetration, an insufficient amount of time for the drug to remain at the target, and drug instability. In response to intrinsic biological stimuli in diseased epidermal tissues, stimuli-responsive nanocarriers also called intelligent or smart delivery systems emerged to overcome these limitations and deliver various therapeutic agents.</p><p><strong>Methods: </strong>In this study, the literature on internal stimuli-responsive nanocarriers for dermal and transdermal delivery reported in review articles/research articles from 2015 to 2026 was reviewed using Google Scholar, ScienceDirect, and PubMed as the primary databases. Relevant patents were identified by using Espacenet and Google Patents. There was no systematic quantitative synthesis, but important data were presented following qualitative synthesis.</p><p><strong>Results: </strong>Enzyme-responsive systems for hyaluronidase, matrix metalloproteinases, and lipases were developed for targeted drug delivery to infection and inflammation sites. pH-sensitive nanocarriers used the acidic change in diseased skin for enhanced penetration and improved therapeutic efficiency. Glucose-responsive systems are promising to facilitate the targeted delivery of drugs to promote healing of diabetic wounds in hyperglycemia. Furthermore, drug delivery was controlled by redox-sensitive transporters, which benefited from the high levels of glutathione and reactive oxygen species in inflammatory skin.</p><p><strong>Discussion: </strong>Longer cutaneous residency, less systemic exposure, and lower therapeutic dosages may explain why these smart systems may outperform conventional formulations. A relatively new development in dermatological care is the integration of multiple response systems into one platform.</p><p><strong>Conclusion: </strong>Internal stimuli-responsive nanocarriers are an alternative strategy for the treatment of skin diseases by combining the delivery of drug molecules with disease-specific biological signals. This new strategy may enable safer and more efficient dermal and transdermal delivery of a wide range of medicinal compounds.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}