{"title":"Current Updates on Recent Developments in Artificial Intelligence in QSAR Modelling for Drug Discovery against Lung Cancer.","authors":"Deepanshi Chaudhary, Chakresh Kumar Jain","doi":"10.2174/0115680266391548250930172321","DOIUrl":"https://doi.org/10.2174/0115680266391548250930172321","url":null,"abstract":"<p><p>Lung cancer continues to be a leading cause of cancer-related mortality worldwide, underscoring the urgency for innovative and targeted drug discovery strategies. This review critically explores the role of Quantitative Structure-Activity Relationship (QSAR) modelling, particularly its integration with artificial intelligence (AI), in accelerating the identification and optimization of lung cancer therapeutics. Recent progress in multi-target approaches, machine learning (ML) algorithms with mathematical representations, and molecular descriptor engineering has been analyzed, with a special focus on clinical translations. Rather than offering a generic overview, we evaluate how AI-powered QSAR addresses key bottlenecks in drug development, such as data imbalance, model interpretability, and ADMET prediction failures. Notable case studies are examined to highlight translational success stories in lung cancer-specific pathways. This review offers a cohesive synthesis of current advancements, identifies critical gaps and limitations, and proposes future directions for enhancing the real-world applications of QSAR methodologies in oncological drug discovery.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344139","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":"Review on Harnessing Silver Nanoparticles for Therapeutic Innovations: A Comprehensive Review on Medical Applications, Safety, and Future Directions.","authors":"Muhammad Raza, Hyang Yeol Lee","doi":"10.2174/0115680266405632250929122554","DOIUrl":"https://doi.org/10.2174/0115680266405632250929122554","url":null,"abstract":"<p><p>A novel class of nanomaterials known as silver nanoparticles (AgNPs) changes the potential in modern medicine. AgNPs are rapidly gaining significance in therapeutic applications ranging from tissue engineering to drug delivery systems due to their strong antibacterial, anticancer, anti-inflammatory, and wound-healing properties. This review presents a comprehensive analysis of the biomedical potential of AgNPs, physical, chemical and biological features that allow for regulated release mechanisms, improved bioavailability, and selective cellular targeting. Considering their obvious promise, there are significant challenges due to concerns about longterm exposure, toxicity, and regulatory uncertainty. We cover new developments, clinical studies, and safety evaluations, providing a balanced perspective of the advantages and disadvantages of AgNP or drug-based therapies. This review proposes a framework for scientists, physicians, and legislators to harness the full therapeutic power of silver nanoparticles while directing associated risks.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344062","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":"Bacterial Nanocellulose Membranes for Codelivery of Carvacrol and Thymol: Physico-chemical Characterization and In vitro Studies.","authors":"Gabbai-Armelin Paulo Roberto, De Oliveira Analú Barros, Rodero Camila Fernanda, Silva Jhonatan Miguel, Fernandes Natalie Aparecida Rodrigues, Paiva Robert, Dametto Alessandra Cristina, Chorilli Marlus, Barud Hernane da Silva, Brighenti Fernanda Lourenção","doi":"10.2174/0115680266377999250929122859","DOIUrl":"https://doi.org/10.2174/0115680266377999250929122859","url":null,"abstract":"<p><strong>Introduction: </strong>Skin wounds represent a worldwide problem. Biopolymers have been attracting interest in healthcare products for wound dressing. Among these, bacterial nanocellulose membranes (BNC) are attractive for their unique structure, but they lack antimicrobial activity. Thus, the incorporation of the monoterpenes Carvacrol (Car) and Thymol (Thy) - which present antimicrobial and healing properties - toward the improvement of skin wound healing, consists of an appealing approach. This research aimed to produce and characterize nanocellulose membranes containing carvacrol and/or thymol, and investigate their release behavior, cytotoxicity, and antimicrobial properties.</p><p><strong>Method: </strong>BNC/Car, BNC/Thy, and BNC/Car-Thy membranes were produced at doses of 0.1 and 1.0 mg/cm2.</p><p><strong>Results: </strong>The natural components incorporation into the nanocellulose did not interfere with the ultra-structure or its physical characteristics. Pilot studies showed that membranes with 1.0 mg/cm² of monoterpenes were toxic to fibroblasts. Therefore, all further studies used the lower dose of 0.1 mg/cm². Release experiments showed a burst release between 2-4 h with sustained release till 24 h, reaching around 80% of the initial amount of the incorporated monoterpenes. Studies with fibroblast and keratinocytes indicated no cytotoxicity and that cells could proliferate over the BNC/Car- Thy membranes. Microbiological studies suggested some antimicrobial potential of the BNC doped with Car and Thy.</p><p><strong>Discussion: </strong>BNC membranes incorporated with Car and Thy were successfully produced and the monoterpenes incorporation into the BNC did not interfere with either ultra-structure or with its physico- chemical characteristics. Natural products incorporation induced cell proliferation and presented antimicrobial properties, besides increasing the solubility and stability of these natural compounds.</p><p><strong>Conclusion: </strong>This innovative biomaterial has the potential for healthcare products.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344061","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":"Zingerone Induces Apoptosis and Ferroptosis in Prostate Cancer DU145 Cells.","authors":"Nawaf Alshammari, Meenakshi Verma, Motrih Al-Mutiry, Sorabh Lakhanpal, Suhas Ballal, Anurag Kumar Singh, Renu Arya, Mohd Saeed, Pratibha Pandey, Fahad Khan","doi":"10.2174/0115680266411570250929101928","DOIUrl":"https://doi.org/10.2174/0115680266411570250929101928","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer is among the most prominent malignant tumors in the male population, characterized by growing morbidity, a high fatality rate, and currently limited therapeutic options, necessitating the urgent development of novel clinical medications. The objective of the current study was to examine the therapeutic potential of zingerone in prostate cancer cells.</p><p><strong>Methods: </strong>In this study, we investigated the underlying mechanism by which zingerone exerts its anticancer effects in prostate cancer cells. We conducted various in vitro and in silico experiments to determine the therapeutic efficacy and mechanism of action of zingerone.</p><p><strong>Results: </strong>Cytotoxicity analysis of zingerone revealed its substantial cytotoxic impact and ability to elevate lactose dehydrogenase levels in DU145 cells. Using the MTT assay, we determined that a concentration of 24.84 μM zingerone in DU145 cells grown for 24 h resulted in an IC50 value. Zingerone effectively induced apoptosis by increasing the levels of cytochrome c and caspase in DU145 cells. Regarding the identification of signs of ferroptosis, evidence has been shown for the presence of heightened mitochondrial ROS, disrupted mitochondrial membrane potential, increased levels of glutathione (GSH) and malondialdehyde (MDA), and reduced expression of SCL7A11 and GPX4.</p><p><strong>Discussion: </strong>Importantly, our study confirms that zingerone triggered both apoptosis and ferroptosis in DU145 cells by downregulating SLC7A11 and GPX4 expression.</p><p><strong>Conclusion: </strong>This study provides evidence that makes zingerone a potent therapeutic agent for prostate cancer.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328161","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":"Ethyl Acetate Extract from Wenxia Formula (WFEA) Attenuates Immunosuppression in Lung Cancer by Inhibiting Treg Differentiation via Blockade of TGF-Β/Smad Signaling.","authors":"Meng Wang, Xiangyu Han, Hui Li, Bin Zheng, Dongdong Fang, Shulong Jiang","doi":"10.2174/0115680266415173251010101905","DOIUrl":"https://doi.org/10.2174/0115680266415173251010101905","url":null,"abstract":"<p><strong>Introduction: </strong>The ethyl acetate extract of Wenxia Formula (WFEA) is the most effective antitumor component of the Wenxia formula. Its key active components, emodin and quercetin, exhibit unique advantages in targeting TGF-β1 and regulating the function of Tregs. This study explored the mechanism of WFEA in enhancing the immune environment in lung cancer by influencing immune cell balance and the level of cytokines.</p><p><strong>Materials and methods: </strong>Lewis lung cancer xenograft mouse models were established. WFEA was administered at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, while a cisplatin (DDP) group served as the positive control. Tumor weight, spleen index, and serum cytokine levels (IL-10, TGF-β1) were measured. Flow cytometry, qPCR, and immunohistochemistry were employed to analyze the proportion of CD4⁺CD25⁺Foxp3⁺ Treg cells and Foxp3 expression in tumor and spleen tissues. The regulatory mechanism of WFEA on the TGF-β/Smads signaling pathway was investigated via combined intervention with the TGF-β1 inhibitor halofuginone (HF), cell differentiation assays, and molecular docking analyses.</p><p><strong>Results: </strong>WFEA inhibited tumor growth in a dose-dependent manner, with the 400 mg/kg group exhibiting a 60% tumor inhibition rate comparable to that of DDP. The agent significantly increased the spleen index by 106.42% and reduced serum levels of IL-10 and TGF-β1. Mechanistically, WFEA downregulated Foxp3 mRNA and protein expression in both tumor and spleen tissues, leading to a decrease in the proportion of Treg cells. It blocked the TGF-β/Smads pathway by downregulating TGF-β1, upregulating Smad4/Smad7, and inhibiting Smad2/3 phosphorylation. Cell-based experiments confirmed that WFEA-containing serum inhibited the differentiation of CD4⁺ T cells into Tregs, an effect enhanced by TGF-β1 interference. Molecular docking analyses revealed that the active components emodin and quercetin directly bound to TGF-β1 with binding energies of -5.4 kcal/mol and -5.1 kcal/mol, respectively.</p><p><strong>Discussion: </strong>WFEA could serve as a new adjunct treatment for lung cancer; however, further clinical trials are required to evaluate its long-term safety and effectiveness across various treatment stages.</p><p><strong>Conclusion: </strong>WFEA may regulate the growth of Tregs to modulate the immune microenvironment of the LLC model mice, indicating its potential as an anti-LLC agent.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328180","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":"Traditional Design and Modification of \"Celastrol\" Nano-Delivery Systems for Cancer: A Review.","authors":"Siu Kan Law, Sze Wing Ng, Yanping Wang, Xiao Xiao Wu","doi":"10.2174/0115680266418981250929223913","DOIUrl":"https://doi.org/10.2174/0115680266418981250929223913","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer is a prevalent public health issue and a significant global problem. Patients receive different treatments, including Western Medicine (WM) and Traditional Chinese Medicine (TCM). This review article aims to discuss a Traditional Chinese Medicine (TCM), \"Celastrol,\" its traditional design, modification, and nano-drug delivery systems for the treatment of cancer.</p><p><strong>Methods: </strong>Nine electronic databases, such as WanFang Data, PubMed, ScienceDirect, Scopus, Web of Science, SpringerLink, SciFinder, and China National Knowledge Infrastructure (CNKI), were used to find relevant information from the past twenty years, with searched keywords including \"celastrol,\" \"cancer,\" and \"nano-drug delivery system,\" etc., without language restrictions.</p><p><strong>Results: </strong>Celastrol is a therapeutic agent with anticancer properties against liver and breast cancers, ovarian cancer, multiple myeloma, and glioma. PI3K/Akt/mTOR, Bcl-2/Bax-caspases, EGFR, ROS/JNK, NF-κB, STAT3, JNK/Nrf2/HO-1, VEGF, AR/miR-101, HSF1-LKB1-AMPKα-YAP, Wnt/β-catenin, and CIP2A/c-MYC signaling pathways are the possible mechanisms by which celastrol acts against cancer.</p><p><strong>Conclusion: </strong>A naturally occurring bioactive substance, \"celastrol,\" is extracted from the root of Tripterygium wilfordii Hook F. Its effectiveness can be enhanced with the support of nanotechnology to overcome its limitations in cancer treatment. However, the toxicity, dosage, and safety assessments of celastrol and nanocelastrol in cancer applications must be further investigated.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307174","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":"Pharmacodynamic Interactions: Mechanisms, Clinical Trial Insights, and Patent Perspectives.","authors":"Smita Narwal, Dushyant -, Gurvirender Singh, Nisha Grewal, Vishal Chanalia, Ashwani K Dhingra","doi":"10.2174/0115680266384427250923131856","DOIUrl":"https://doi.org/10.2174/0115680266384427250923131856","url":null,"abstract":"<p><p>Pharmacodynamic interactions are relevant in improving drug efficiency without a significant increase in the effects due to toxicity and, in most, are associated with polypharmacy. Mechanisms that govern pharmacodynamic interactions are additive, synergistic, and also antagonistic. Additive drug interactions refer to effects similar to a summation of effects resulting from administering a pair of drugs or a series, while synergistic describes a heightened response much above what one might have aspired to in light of expectations about additivity. However, the antagonistic effect may weaken therapeutic activity at times. Mechanistic pathways like receptor binding, enzyme inhibition, and modulation of signaling pathways were also studied to bring out their relevance in clinical applications. The manuscript is conscious of the role of patents and clinical trials in understanding pharmacodynamic interactions. Patents provide insight into new drug combinations and mechanisms, and the same interaction gets validated through the outcome of clinical trials. Examples that prove clinical relevance have emerged through the synergy in the usage of the drugs for oncology, cisplatin and etoposide, or the additive effect of aspirin and clopidogrel in preventing thrombotic events. The transformative approaches applied in developing drugs include network pharmacology, epigenetics, and receptor crosstalk. In this review, the pharmacodynamic interactions, by integrating mechanistic insights with clinical data, patents, and case studies, explicitly underpin pharmacodynamic interactions as a factor that enhances drug safety, efficacy, and therapeutic precision.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291588","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}
Shimin Wang, Yuanbo Hu, Carl K Edwards Iii, Yimin Guo, Hai Qin, Bicheng Jin
{"title":"Interleukin-10 Promotes Treg Formation and Tumorigenesis via Regulating Nrp-1/PDX1/FoxP3 Axis: Insights from Integrative Data Analysis.","authors":"Shimin Wang, Yuanbo Hu, Carl K Edwards Iii, Yimin Guo, Hai Qin, Bicheng Jin","doi":"10.2174/0115680266401850250927084313","DOIUrl":"https://doi.org/10.2174/0115680266401850250927084313","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to explore the mechanisms by which interleukin-10 (IL- 10) influences tumorigenesis through T regulatory cells (Treg) regulation.</p><p><strong>Background: </strong>Environmental factors, such as IL-10, significantly shape the immune microenvironment and tumor progression, yet the regulatory pathways remain unclear.</p><p><strong>Objective: </strong>1) To elucidate the regulatory mechanism of IL-10 on Treg cells through in vitro assays; 2) To elaborate whether Nrp-1/PDX1 knockout affects tumorigenesis via in vivo assays.</p><p><strong>Methods: </strong>CD4+ T cells were isolated from the healthy mice's spleen and induced to differentiate into Treg cells. Then, after being treated with IL-10 and mouse melanoma cell supernatant (CM), the expression levels of Nrp-1 and FoxP3 in Treg cells were examined via qRT-PCR and Western blotting. The ratio of Treg cells was measured by flow cytometry. The interaction between Nrp-1 and PDX1 proteins was detected through GST pull-down assay, Co-IP, Western blotting and immunofluorescence staining. STAT3 luciferase activity was detected, and the expression levels of JAK1 and STAT1 proteins were detected by Western blotting. Furthermore, the B16-bearing melanoma mice and Nrp-1/PDX1 knockout mice model were established to verify the effects of Nrp-1 and PDX1 on Treg formation and tumor development.</p><p><strong>Results: </strong>The results demonstrated that IL-10 promoted Nrp-1 expression in Treg cells via the JAKSTAT3 signaling pathway. Nrp-1 could combine with PDX1 to form a complex, facilitating PDX1-mediated activation of FoxP3 and Treg production. In melanoma xenograft models, targeting Nrp-1 and PDX1 using shRNAs or antibodies significantly reduced Treg levels and inhibited tumor growth. Collectively, IL-10 promotes Treg formation and tumorigenesis via regulating Nrp- 1/PDX1/FoxP3 axis.</p><p><strong>Discussion: </strong>This study was the first to identify the interaction between Nrp-1 and PDX1, leading to PDX1 ubiquitination, which enhanced FoxP3 expression and Treg function in the tumor microenvironment. These novel insights highlighted the Nrp-1/PDX1/FoxP3 axis as a critical regulator of Treg-mediated tumorigenesis, offering potential targets for cancer therapy.</p><p><strong>Conclusion: </strong>These findings highlight the interplay between environmental influences and immune regulation, providing novel insights into Treg-mediated tumorigenesis and suggesting potential strategies for targeted therapy.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291605","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}
Mazen M Jamil Al-Obaidi, Tanweer Al Zuhaibi, Hoor Al Wahshi
{"title":"Ellagic Acid as a Therapeutic Agent for Blood-Brain Barrier Restoration in Neurodegenerative Diseases.","authors":"Mazen M Jamil Al-Obaidi, Tanweer Al Zuhaibi, Hoor Al Wahshi","doi":"10.2174/0115680266411446250926102553","DOIUrl":"https://doi.org/10.2174/0115680266411446250926102553","url":null,"abstract":"<p><p>The Blood-Brain Barrier (BBB) plays a crucial role in maintaining the stability of the Central Nervous System (CNS) by regulating what enters and protecting the brain from inflammation and damage caused by harmful molecules. The disruption of the BBB is a characteristic feature of several neurodegenerative disorders and is intimately linked to oxidative stress, inflammation, and apoptosis. Ellagic Acid (EA), a polyphenolic molecule present in several fruits and nuts, has attracted interest due to its significant antioxidant, anti-inflammatory, and neuroprotective characteristics. This review examine recent findings on how EA might help keep the BBB healthy and reduce brain damage. EA works by increasing the levels of tight junction proteins, boosting antioxidant processes, and managing cell death pathways. The review also discusses EA's limited bioavailability and emphasises the therapeutic potential of its gut-derived metabolites, urolithins, which demonstrate enhanced stability and cellular transport. Although EA has considerable potential as a neuroprotective drug, its translational use necessitates more research into its pharmacokinetics, delivery mechanisms, and therapeutic effectiveness. A comprehensive understanding of EA's molecular processes, especially in brain microvascular endothelial cells, may provide innovative therapeutic approaches for safeguarding the BBB and addressing neurodegenerative disorders.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291591","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":"Isatin Derivatives as Emerging Promising Anti-Alzheimer Agents: Focusing on Their Chemical Structure and Biological Targets.","authors":"Yasaman Tamaddon-Abibigloo, Siavoush Dastmalchi, Fardin Mahdipanah, Elham Asadi, Sadegh Khezrpour, Pardis Valizadeh, Javid Shahbazi-Mojarrad","doi":"10.2174/0115680266394265250828164308","DOIUrl":"https://doi.org/10.2174/0115680266394265250828164308","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder with a complex pathology. Until now, there is no generally effective treatment for AD. Isatin is a natural alkaloid whose derivatives have shown a wide spectrum of biological activities. This molecule is also the basic scaffold for several compounds with useful biological properties against AD. In this review, for the first time, we focus on the anti-AD properties of isatin derivatives. We tried to present comprehensive data about their structure and mechanism of action. Results showed that indirubins, isatin Schiff Bases, and spiro derivatives of isatin were the most studied molecules. The most studied targets were the glycogen synthase kinase-3, cholinesterases, and amyloid beta aggregation. It was concluded that isatin could be considered an important scaffold for the development of new anti-AD compounds.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285820","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}