Current topics in medicinal chemistry最新文献

{"title":"Justicidin: A Versatile Arylnaphthalene Lignan with Broad-Spectrum Anticancer and Chronic Disease Potential.","authors":"Navin Kumar Tailor","doi":"10.2174/0115680266443696260407110205","DOIUrl":"https://doi.org/10.2174/0115680266443696260407110205","url":null,"abstract":"<p><p>Justicidins are naturally occurring arylnaphthalene lignans, mainly from Justicia, Phyllanthus, and Linum species. Justicidin and its derivatives have gained scientific attention for their structural adaptability and wide-ranging pharmacological activities. Their rigid arylnaphthalene core, featuring hydroxyl, methoxy, dioxymethylene groups, and a five-membered lactone ring, offers chemical stability and scope for modification, enabling targeted drug design. Preclinical studies show that justicidin has potent cytotoxicity against breast, lung, leukemia, colorectal, and bladder cancer cells through mechanisms such as apoptosis induction via mitochondrial pathways, topoisomerase inhibition, cell cycle modulation, angiogenesis suppression, and interference with metastasis-related signaling. Beyond oncology, it demonstrates anti-inflammatory, antiviral, neuroprotective, antibacterial, antiplatelet, and antiangiogenic effects. Its multi-target activity involves modulation of NF-κB, MAPK, and PI3K/Akt pathways, as well as DNA damage induction, mitochondrial membrane potential disruption, and regulation of caspases. Low toxicity in normal cells and favorable pharmacokinetics in experimental models strengthen its therapeutic promise. Advances in total synthesis and biotechnological production further enhance its research value. This review compiles current insights into the chemistry, biosynthesis, biotechnological production, pharmacology, and molecular mechanisms of justicidin, underscoring its dual potential as an anticancer lead and a versatile agent for chronic diseases. Understanding structure-activity relationships and optimizing drug-like properties may enable the development of novel, multi-target therapeutics inspired by this natural product.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971388","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":"Ophiocordyceps sinensis in Cancer Therapy: Bridging Traditional Medicine and Modern Oncology.","authors":"Vatan Chaudhary, Atul Pratap Singh, Himanchal Sharma, Dhananjay Taumar, Anshu, Iram Rajpoot","doi":"10.2174/0115680266402650251110114152","DOIUrl":"https://doi.org/10.2174/0115680266402650251110114152","url":null,"abstract":"<p><strong>Introduction: </strong>Ophiocordyceps sinensis, a parasitic fungus traditionally used in Asian medicine, has drawn attention for its potential anticancer properties. Its bioactive components- such as cordycepin, polysaccharides, and nucleosides-exhibit anti-inflammatory, antioxidant, immunomodulatory, and anticancer activities.</p><p><strong>Methods: </strong>This study reviews preclinical evidence from in vitro and in vivo models evaluating the anticancer effects of O. sinensis against various cancers, including lung, breast, liver, and colon. Mechanistic assessments focused on apoptosis induction, cell cycle regulation, angiogenesis inhibition, and immune modulation.</p><p><strong>Results: </strong>Cordycepin, a key active compound, was found to induce apoptosis via caspase activation and Bcl-2 family protein modulation. Additionally, O. sinensis inhibited angiogenesis, disrupted cancer cell proliferation through cell cycle arrest, and reduced oxidative stress. Its immunomodulatory effects were also noted to enhance anti-tumor immune responses. Some studies suggest it may potentiate traditional cancer therapies by mitigating treatment-induced immunosuppression and tissue damage.</p><p><strong>Discussion: </strong>These preclinical findings highlight O. sinensis as a promising natural anticancer agent. Its multifaceted mechanisms align with modern therapeutic goals such as immune engagement and tumor microenvironment modulation. However, current evidence is limited to preclinical settings. Variability in bioactive compound content and concerns about bioavailability remain major challenges.</p><p><strong>Conclusion: </strong>Ophiocordyceps sinensis demonstrates encouraging anticancer potential in preclinical models. Further clinical studies are essential to validate its efficacy, establish safety profiles, and optimize formulation for therapeutic use.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970798","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":"HDAC Inhibitors in Hematological and Solid Tumor Therapy: Current Success, Challenges, and Future Directions.","authors":"Vaibhav Singh, Shadiya Parveen, Vijay K Patel, Ekta Shirbhate, Ravichandran Veerasamy, Amit K Tiwari, Harish Rajak","doi":"10.2174/0115680266385393251115155753","DOIUrl":"https://doi.org/10.2174/0115680266385393251115155753","url":null,"abstract":"<p><p>The abnormal HDAC activity contributes to the induction of cancer by disturbing normal cellular processes and inhibiting tumor suppressor genes. With considerable potential in both haematological malignancies and solid tumors, histone deacetylase (HDAC) inhibitors have become an attractive epigenetic regulator in cancer treatment. This comprehensive study examines the molecular diversity of HDAC inhibitors across different cancer types, utilizing DNA methylation, histone modification, and miRNA regulation, thereby highlighting their role in altering epigenetic landscapes. The study investigates the differential efficacy between hematological tumors, where therapeutic applications are well-established, and solid tumors, where pharmacokinetic limitations still exist. The review examines new developments in combination therapy and their effects on the tumour microenvironment, particularly on the synergistic effects of HDAC inhibitors with targeted medicines and immunotherapeutics. It also discusses new therapeutic approaches based on selective HDAC inhibitors targeting specific isoforms, such as HDAC6 and HDAC11, in metabolically active tumors. Resistance mechanisms, biomarker-driven patient selection, and improvement of solid tumour delivery systems remain significant challenges. With expert perspectives on future developments, this study concludes by highlighting the need for the development of more selective inhibitors with improved pharmacokinetic properties and the optimization of combination methods for personalized cancer treatment approaches.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940693","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":"Selective Targeting of SARS-CoV-2 Spike Protein by Isatin-Hydrazide Hybrids: Synergistic In vitro and Molecular Dynamics Approaches.","authors":"Saeed Ullah, Atta Ullah, Sobia Ahsan Halim, Syeda Bakhtawar Zahra, Suraj N Mali, Oussama Abchir, Samir Chtita, Magda H Abdellattif, Rima D Alharthy, Mohammad Zubair, Mesaik M Ahmed, Ajmal Khan, Ahmed Al-Harrasi, Zahid Shafiq","doi":"10.2174/0115680266387685251103021903","DOIUrl":"https://doi.org/10.2174/0115680266387685251103021903","url":null,"abstract":"<p><strong>Introduction: </strong>SARS-CoV-2 has significantly impacted people's lives worldwide. The viral genome has undergone numerous unanticipated changes that have led to the creation of new varieties and raised concerns across the globe. As the bioactive phytochemicals from both natural and synthetic origins have become a promising therapeutic approach due to their high ability to suppress pathogenic viruses.</p><p><strong>Methods: </strong>The current work reports 9 novel isatin hydrazide conjugates as inhibitors of the SARSCoV- 2 spike protein, using in vitro and in silico approaches.</p><p><strong>Results: </strong>It's interesting to note that, except for compounds 3a, 3e, and 3h all the remaining compounds showed significant to high inhibition, with inhibitory values ranging from 91.50 to 77.40 %. Here, compounds 3b (86.80 %), 3c (89.30 %), 3d (81.60 %), 3f (87.30 %), 3g (84.40 %), 3i (91.50 %), and compound 3l (85.49 %) resulted in high inhibitory potential. While 3j compound with 77.40 % inhibition significantly inhibited the SARS-CoV-2 spike protein. With docking scores ranging from -7.1 to -9.1 kcal/mol, the molecular docking of these compounds showed an excellent fit of molecules in the spike protein receptor binding domain (RBD) with good interactions with the RBD's essential residues. Additionally, a 100 ns molecular dynamics simulation showed that the complexes 3i-6M0J and Narlaprevir-6M0J were highly stable.</p><p><strong>Discussion: </strong>This study highlights the prospective therapeutic potential of new isatin hydrazide conjugates for the treatment of COVID-19 by identifying them as strong SARS-CoV-2 spike protein inhibitors that have been confirmed by docking and molecular dynamics.</p><p><strong>Conclusion: </strong>The results of these in vitro and in silico experiments suggest their medical potential in treating SARS-CoV-2 infection with high potency. Therefore, these tiny compounds have the potential to be therapeutic agents.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940721","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":"Unraveling the Global Research Trajectory of Microalgae Stimulation for Enhanced Production of Bioactive Compounds.","authors":"Kabari Krishna Borah, Baby Gargi, Manisha Nanda, Prabhakar Semwal","doi":"10.2174/0115680266397288251204160221","DOIUrl":"https://doi.org/10.2174/0115680266397288251204160221","url":null,"abstract":"<p><strong>Introduction: </strong>Microalgae have emerged as a potential candidate for environmental remediation and as a source of value-added products. Exogenous phytohormone supplementation in microalgae regulates biological processes and induces various signal transduction pathways. This study uses the Scopus database to identify key contributors, advance research areas, and analyze global trends in microalgal cell stimulation for bioactive compound production over 14 years.</p><p><strong>Materials and methods: </strong>Our study started with a search using the keywords \"Microalgae,\" \"Phytohormone,\" \"Heavy metal,\" \"Metal tolerance,\" \"Biomass,\" \"Growth,\" \"Pigment,\" and \"Lipid,\" retrieving studies from the Scopus database published between 2010 and 2024. Bibliometric tools such as VOSviewer and Bibliometrix were employed to analyze and evaluate the obtained documents.</p><p><strong>Results: </strong>The initial search yielded 283 documents, including research and review articles, and after extensive screening, 217 publications remained for analysis. China stands out as a major contributing country, and the Kunming University of Science and Technology is leading the field. Bioresource Technology and the Journal of Applied Phycology are the top journals in the study domain.</p><p><strong>Discussion: </strong>Microalgae demonstrate high efficiency in nutrient removal, heavy metal bioremediation, CO₂ sequestration, and the reduction of emerging contaminants. Advanced multiomics approaches will help mitigate microalgal stress responses and support the design of more effective microalgae-bacteria consortia for wastewater treatment. Researchers should focus on targeted studies of metabolic pathways and genetic regulation in response to environmental stressors.</p><p><strong>Conclusion: </strong>The present study will be a valuable contribution to the field of microalgal biotechnology and in understanding their relationship with phytohormones for enhancing the biosynthesis of bioactive compounds.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940094","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 Review of Pathophysiology and Computational Studies of Isoeugenol Derived Acetamides against Alzheimer's Disease.","authors":"Arthur Lins Dias, Pablo Rayff da Silva, Hugo Fernandes Oliveira Pires, Livia Roberta Pimenta Souza, Natália Ferreira de Sousa, Alan Ferreira Alves, Jéssica Cabral de Andrade, Luiza Cristine Diniz Neri, Maria Clara Ferreira Goncalves, Cícero Francisco Bezerra Felipe, Mirian Graciela da Silva Stiebbe Salvadori, Marcus T Scotti, Luciana Scotti","doi":"10.2174/0115680266400065251208095300","DOIUrl":"https://doi.org/10.2174/0115680266400065251208095300","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disesase (AD) is a neurodegenerative disorder characterized by a deterioration of cognitive fuction, memory loss, and behavioral changes. The current pharmacotherapy is limited and focuses only on symptom relief. Therefore, this study aimed to review the targets involved in Alzheimer's disease (AD) and evaluate the pharmacokinetics and potential interactions of isoeugenol and nine hybrid acetamides derived from it. The pharmacokinetic profiles of the compounds were assessed using ADMET analysis through Deep-PK. For molecular docking, nine hybrid acetamide derivatives of isoeugenol and molecular targets implicated in AD pathophysiology were selected for consensus analysis. All compounds were predicted to exhibit satisfactory pharmacokinetic properties, including good intestinal absorption and blood-brain barrier penetrability. Regarding the toxicological profile, a few derivatives showed potential toxic effects. According to the molecular docking results, the derivatives exhibited satisfactory interactions with five key targets involved in Alzheimer's disease pathophysiology: apoE4, GABAA, e-NOS, i-NOS, and n-NOS, suggesting potential activity through these pathways. Notably, several compounds showed significant potential activity via the nitric oxide (NO) pathway. The studied compounds demonstrated a favorable pharmacokinetic profile and a high in silico likelihood of modulating Alzheimer's disease-related pathways, highlighting their potential as candidates for further in vitro and in vivo investigations.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940554","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":"Classical Docking to Machine Learning Based Docking: Molecular Docking in Drug Discovery.","authors":"Partha Pratim Gogoi, Basanta Singha, Penlisola Longkumer, Nichan Boruah, Upasana Bora Sinha","doi":"10.2174/0115680266424314251204071847","DOIUrl":"https://doi.org/10.2174/0115680266424314251204071847","url":null,"abstract":"<p><p>Molecular docking has emerged as a cornerstone methodology in computational drug discovery, enabling the prediction of ligand-receptor interactions with considerable accuracy and efficiency. This article provides a comprehensive overview of docking fundamentals, including its workflow, scoring functions, and various types, ranging from rigid to flexible and ensemble docking approaches. Docking serves as an essential tool for virtual screening, lead optimization, and structure-based drug design, significantly reducing experimental costs and accelerating the identification of therapeutic candidates. The review details contemporary scoring strategies such as force-field-based, empirical, knowledge-based, and consensus scoring, highlighting their respective strengths and documented limitations. Additionally, a comparative evaluation of widely used docking platforms such as AutoDock, MOE, GOLD, Glide, and MVD is presented, incorporating recent benchmarking results and practical considerations. Special emphasis is placed on the integration of molecular docking with machine learning, artificial intelligence, molecular dynamics simulations, and other computational methods. Innovations such as deep learning architectures, AlphaFold-based structural modeling, reinforcement learning, and cloud-based high-throughput screening are redefining the predictive power, scalability, and clinical relevance of docking. Applications extend across drug discovery, drug repurposing, natural product research, and personalized medicine. The article also discusses critical challenges such as protein flexibility and scoring inaccuracies, and reviews emerging hybrid solutions designed to enhance accuracy and reliability. The review underscores the transformative impact of molecular docking in modern drug development.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940647","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":"Arbutin as a Therapeutic Agent: Protein Modulating Potential and Pharmacology Perspective.","authors":"Sonia Singh, Suman Sinha, Ashima Ahuja, Lokesh Ranjan","doi":"10.2174/0115680266439033260406075534","DOIUrl":"https://doi.org/10.2174/0115680266439033260406075534","url":null,"abstract":"<p><p>Arbutin, a glycosylated hydroquinone derivative, has garnered considerable attention for its pharmacological versatility. Initially popularized for its depigmenting effects in dermatology, arbutin has since been explored for a broad spectrum of biological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, and neuroprotective properties. This review consolidates recent findings on arbutin's pharmacodynamics, mechanisms of action, and potential therapeutic applications, emphasizing its relevance in modern pharmacological research. This manuscript describes the biochemical pathways of arbutin, as well as its absorption, distribution, metabolism, and excretion. Furthermore, the toxicity concerns associated with various challenges in clinical translation warrant further screening. Researchers must focus on developing novel dosage forms and innovative strategies to enhance the therapeutic outcomes of arbutin in modern pharmacological research. Arbutin is a promising natural therapeutic drug with several biomedical uses, but further studies in molecular pharmacology, nanotechnology, and clinical evaluation are needed to optimise its therapeutic potential.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940566","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":"Balancing the Risks and Rewards of Carbon Nanotubes in Cancer Applications.","authors":"Dasari Vasavi Devi, Prema S, Ilango K, Ronald Darwin C, Shaik Shafiya Begum, Vasanth Kumar Mohan","doi":"10.2174/0115680266433600260331211310","DOIUrl":"https://doi.org/10.2174/0115680266433600260331211310","url":null,"abstract":"<p><p>Carbon nanotubes (CNTs), which possess their characteristic structural, electrical, and chemical properties, have become flexible nanomaterials in the theranostics of cancer. They can deliver drugs precisely to their intended target due to their high surface area, tunable surface chemistry, and biological intactness through their ability to cross biological barriers and enhance imaging, as well as enabling new forms of treatment, including photothermal therapy and photodynamic therapy. The clinical efficacy of these light-based modalities is, however, limited because the shallow penetration of the light in the near-infrared (NIR) light can diminish the efficacy of treatment on tumours that are deep-seated. The physicochemical properties that predispose CNTs to be useful in treating the human body also provoke valid questions about the safety of this approach in the long-term, especially concerning carcinogenic effects. This review has critically discussed the dual nature of CNTs in oncology, synthesizing the current developments in the therapeutic applications of CNTs, and describes mechanistic insights about their toxicity. CNTs are used to enhance cancer therapy in terms of their application as drug carriers, radiosensitizers, and immune modulators, and comment on their diagnostic application in multimodal imaging. The CNT/PEI/durvalumab nanoagent systems are among them, and they are preclinical studies that have been carried out primarily on animal models. On the other hand, this review evaluates the increasing evidence that links CNT exposure to oxidative stress, mitochondrial malfunctioning, inflammation, epithelial-mesenchymal transition (EMT), and endothelial leakiness pathways that have been implicated in tumorigenesis and metastasis. The review outlines the significance of standardization of functionalization procedures, strict toxicological testing, and the long-term biocompatibility by comparison of therapeutic benefits and biological risks. These risks and benefits have to be weighed to provide a way of balancing the safety of CNT-based nanotechnologies to leap clinical oncology using the resulting experimental models to guide researchers, clinicians, and regulatory officials.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940577","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":"Insight into Recent Methods for Synthesizing Andrographolide Derivatives and their Potential Pharmaceutical Effects.","authors":"Rachit Sharma, Chandana Majee, Rupa Mazumder, Avijit Mazumder, Salahuddin","doi":"10.2174/0115680266424611260417092905","DOIUrl":"https://doi.org/10.2174/0115680266424611260417092905","url":null,"abstract":"<p><strong>Introduction: </strong>Andrographolide (ANDR), a key bioactive compound from Andrographis paniculata, has a long history in traditional medicine but is limited by low bioavailability and solubility. This has sparked significant medicinal chemistry efforts to develop more effective derivatives. This review offers a detailed and current synthesis of ANDR derivatives and their improvements in bioavailability, emphasizing their pharmacological actions, structure-activity relationships, chemical modifications, and patent landscape.</p><p><strong>Method: </strong>The review systematically examines evidence from recent literature and patents, emphasizing chemical strategies for modifying the ANDR scaffold, and summarizes biological evaluation results, including cell-based, in vivo, and mechanistic studies of new synthetic and semi-synthetic compounds.</p><p><strong>Result: </strong>A broad range of ANDR derivatives are described, including C-3, C-12, C-14, and C-19 modifications delivering substantial potency gains across multiple therapeutic areas. Recent analogs demonstrated superior efficacy to the parent compound, such as compound 36e (IC50 = 0.59 µM for MCF-7 cells), compound 41d (ALT = 487.6 IU/L, AST = 742.4 IU/L for hepatoprotection), and compound 19i (IC50 = 0.30 µM for anti-platelet aggregation), far surpassing native ANDR (with typical IC50 8.48 µM or higher). Esterification and hybridization have produced analogs with drastically enhanced inhibition rates (e.g., >85% antifibrotic effect, 93.92% tumor reduction, up to 92% inhibition of bacterial biofilm formation), and several derivatives show reduced cytotoxicity, increased bioavailability, and expanded pharmacological scope.</p><p><strong>Discussion: </strong>The findings suggest that thoughtful modifications to the ANDR scaffold-especially at the C-3, C-12, C-14, and C-19 positions, as well as the lactone moiety-have the potential to enhance potency, selectivity, and pharmacokinetic properties. However, the majority of derivatives remain in the preclinical phase, and challenges such as inadequate solubility, incomplete toxicity assessments, and limited pharmacokinetic data continue to hinder clinical advancement.</p><p><strong>Conclusion: </strong>This review uniquely integrates detailed structure-activity data, advanced synthesis schemes, and quantifiable pharmacological outcomes from recent studies and patents, distinguishing itself from earlier reviews by presenting the most potent, selective, and safest ANDR-based analogs for translational research. The combined focus on numerical efficacy measures and synthetic innovation provides a roadmap for future drug development targeting major human diseases.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940681","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}