Mini reviews in medicinal chemistry最新文献

{"title":"Montmorillonite-supported Reagents: A Powerful and Versatile Platform for the Synthesis of Biologically Active Compounds Our Own Endeavor.","authors":"Aarif L Shaikh, Sachin A Khade, Pallavi D Bhange, Bimal Krishna Banik","doi":"10.2174/0113895575467481260908050131","DOIUrl":"https://doi.org/10.2174/0113895575467481260908050131","url":null,"abstract":"<p><p>This review presents recent advances in montmorillonite-catalyzed organic transformations, highlighting its potential as an efficient, economical and environmentally benign solid-acid catalyst. Montmorillonite and its modified forms effectively promote a wide range of organic reactions, including multicomponent reactions, selective nitration, oxidation and reduction processes, and the synthesis of enamines, pyrroles, and β-lactams. Furthermore, integration with sustainable synthetic approaches such as microwave irradiation, ultrasound-assisted reactions, and solvent-free conditions further enhances reaction rates, improves conversions and selectivities, reduces the formation of undesirable by-products, while limiting the use of hazardous solvents. Particular emphasis is placed on hybrid catalytic systems in which metal salts, such as Bi(NO3)3 and SmI2, are supported on montmorillonite to improve catalytic activity, regioselectivity, and stereoselectivity. These methodologies demonstrate broad synthetic applicability for the preparation of pharmaceutically important compounds, including 1,4-dihydropyridines, β-lactams, aromatic amines, and nitrated derivatives of bioactive molecules such as eugenol and estradiol. Furthermore, a comparative evaluation of catalytic performance and the structural and spectroscopic characteristics of montmorillonite-based materials is also presented. Overall, montmorillonite-supported catalytic systems offer a versatile, efficient, and sustainable platform for advancing environmentally responsible organic synthesis.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Bioactives Targeting α- Synuclein Aggregation in PD: A Review of Multi-mechanism Phytochemicals.","authors":"Shubhanshi Gupta, Rupa Mazumder, Swarupanjali Padhi","doi":"10.2174/0113895575488974260923074226","DOIUrl":"https://doi.org/10.2174/0113895575488974260923074226","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterised by the misfolding and aggregation of α-synuclein, a central pathological event that contributes to oxidative stress, mitochondrial dysfunction, impaired proteostasis, neuroinflammation, synaptic dysfunction and progressive dopaminergic neuronal loss. This review highlights current research on natural bioactive compounds that target α-synuclein aggregation as potential disease-modifying therapies for PD. Relevant material was identified through searches of major scientific databases, including PubMed, Google Scholar, Scopus and Web of Science, focused on research studying natural products and α-synuclein-associated neurodegeneration. The review examines significant types of phytochemicals, including flavonoids, polyphenols, alkaloids, terpenoids, and related natural substances such as baicalein, Epigallocatechin-3-Gallate (EGCG), berberine, curcumin, naringenin, mangiferin, silibinin, and oleuropein etc. Together, these substances have shown a variety of neuroprotective mechanisms in preclinical models such as preventing α-synuclein fibrillization, improving protein clearance pathways, reducing oxidative stress and neuroinflammation, maintaining mitochondrial function, and modifying cellular signalling pathways related to neuronal survival. Important translational obstacles are also highlighted by the current data, such as low oral bioavailability, quick metabolic breakdown, inadequate brain exposure, and the lack of clinical efficacy for several prospective candidates. Most of the information currently available comes from preclinical trials, even though natural bioactive substances constitute a potential avenue of investigation for targeting α- synuclein disease. To determine their therapeutic potential as disease-modifying therapies, more drug-delivery optimisation, pharmacokinetic characteristics, and well-planned clinical studies would be necessary for Parkinson's disease.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Development of Covalent Activators: A Review.","authors":"Amanda Wolbert, Dongwen Lv, Matteo Borgini","doi":"10.2174/0113895575492137260923073122","DOIUrl":"https://doi.org/10.2174/0113895575492137260923073122","url":null,"abstract":"<p><p>While covalent drugs have traditionally been developed as inhibitors, an emerging class of molecules that enhance protein function through covalent modification is attracting increasing attention. This review provides a comprehensive overview of the discovery, design, and development of this class of molecules, surveying key examples across diverse protein families, including nuclear receptors, G Protein-Coupled Receptors (GPCRs), enzymes, and ion channels. We highlight both serendipitously discovered and rationally designed covalent activators, offering insights into their distinct mechanisms of action and enabling their classification into mechanistic categories. We discuss the molecular mechanisms underlying covalent activation, the electrophilic warheads used to achieve target engagement, and the experimental evidence supporting their activity. Particular emphasis is placed on distinguishing examples with therapeutic potential from those that primarily serve as chemical biology tools. Where available, the medicinal chemistry routes of representative covalent activators are discussed, with attention to key considerations in electrophilic warhead installation. While some covalent activators have demonstrated promising pharmacological properties, the field remains at an early stage of development, and the discovery and optimization of these molecules differ fundamentally from those of covalent inhibitors. Accordingly, this review seeks to identify common mechanistic and medicinal chemistry principles that underpin diverse classes of covalent activators. Through comparative analysis across different protein families, we highlight how target biology, structural information, and protein dynamics influence activation strategies, electrophile selection, and activator design, providing a framework that may guide the rational development of future covalent activators. Finally, we discuss emerging opportunities, challenges, and future directions in the discovery and development of covalent activators.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Intelligent Is xCELLigence? Classification of Doxorubicin Cytotoxicity Based on Kinetic Profiling.","authors":"Valeria Ivko, Olga Antipova, Dmitry Usachev, Galina Pavlova, Alexey Kopylov","doi":"10.2174/0113895575497593260923061443","DOIUrl":"https://doi.org/10.2174/0113895575497593260923061443","url":null,"abstract":"<p><p>This mini-review provides a comprehensive analysis of kinetic data from cytotoxicity testing of the conventional anti-proliferative compound doxorubicin (DOX). The value of information provided by xCELLigence Real Time Cell Analysis (RTCA) for performing simple, robust in vitro quantitative kinetic profiling has been estimated, in contrast to the currently most widely used static endpoint assay, such as the MTT assay. It has exquisite sensitivity with easy study of a wide repertoire of label-free molecules and cells, and it is well suited for combination therapy research. Despite numerous publications on xCELLigence technology, focusing on compoundmediated cytotoxicity, combination therapy, cell adhesion, receptor activation, and more, there is a lack of uniformity in descriptions, and the data analysis is insufficient. To identify those gaps and attempt to unify data analysis, DOX was chosen as the reference standard for classification in this mini-review. All results from its cytotoxicity tests across various cell types were analyzed. Three typical scenarios of cell responses (cell index, CI) following APC addition were proposed. Type 1, \"normal response\", shows CI declining. Type 2, \"hump\", shows gradual CI increase above control, then declining. Type 3, \"plateau\" - delayed declining response. Variations of kinetic profiles of CI were analyzed for: DOX itself; DOX in combination with other drugs; physically and chemically modified DOX. The next direction for xCELLigence RTCA method development is a kinetic analysis of changes in cell physiology in drug-treated cells, focusing on early and delayed responses. This focus displacement could reveal novel drug mechanisms of action and kinetics.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcone Derivatives as Multitarget Modulators of Signalling Pathways in Breast Cancer: Mechanisms, Challenges, and Future Perspectives.","authors":"Santanu Shaw, Azra Yasmin, Gouranga Sundar Roy, Sukanta Satapathy, Richa Patel, Purusottam Banjare","doi":"10.2174/0113895575494649260908045603","DOIUrl":"https://doi.org/10.2174/0113895575494649260908045603","url":null,"abstract":"<p><p>Breast cancer continues to be one of the leading causes of morbidity and mortality for women all over the world, noted for its heterogeneity, metastasis, and resistance to conventional therapies. In this regard, chalcone derivatives, which are flavonoids found in nature or synthesized chemically, are emerging as promising anticancer agents due to their ability to modulate multiple oncogenic signaling pathways and their structural flexibility. The current review systematically evaluates chalcone derivatives with respect to modulation of apoptotic pathways, cell cycle arrest, inhibition of angiogenesis and metastasis, reversal of multidrug resistance, and disruption of pathways including PI3K/Akt/mTOR, MAPK/ERK, NF-κB, JAK/STAT, and Wnt/β-catenin. Structure- activity relationship insights are highlighted to explain how chemical modifications influence bioactivity and selectivity. Furthermore, this study discusses the translational barriers, including pharmacokinetic limitations, toxicity concerns, and the need for nanotechnology-based delivery systems. Current progress in hybrid design, computational modeling, and combination therapies underscores chalcones' potential as next-generation breast cancer therapeutics. Despite challenges in clinical translation, chalcone derivatives represent a versatile scaffold capable of overcoming therapeutic resistance and providing a foundation for precision oncology.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzimidazole-based Multi-target Directed Ligands: A Comprehensive Review of Therapeutic Potential in Alzheimer's disease.","authors":"G P Gigi, S Prema","doi":"10.2174/0113895575491724260908101357","DOIUrl":"https://doi.org/10.2174/0113895575491724260908101357","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive decline. Current treatments provide only symptomatic relief and fail to halt disease progression, underscoring the urgent need for disease-modifying interventions. The complex interplay among amyloid-β aggregation, tau hyperphosphorylation, cholinergic dysfunction, oxidative stress, metal dyshomeostasis, and neuroinflammation necessitates multi-target therapeutic strategies. Benzimidazole analogues have emerged as a promising scaffold in this context, owing to their structural flexibility, broad pharmacological activity, and demonstrated multi-target capability. This review critically analyses recent developments in the design, synthesis, and biological evaluation of benzimidazole-based compounds as potential anti-Alzheimer's agents. Particular emphasis is placed on structure-activity relationships governing interactions with key AD-relevant targets, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-secretase (BACE1), tau-related protein kinases, and metal chelation relevant to amyloid pathology. The neuroprotective, antioxidant, and anti-inflammatory properties of these derivatives are also discussed in the context of their potential disease-modifying relevance. The advantages of benzimidazole-based Multi-target Directed Ligands (MTDLs) over conventional single-target approaches are highlighted, particularly their capacity to address multiple pathological hallmarks of AD simultaneously. Key limitations, including pharmacokinetic challenges and the absence of clinical validation, are critically evaluated to provide a balanced perspective. Overall, this review establishes benzimidazole analogues as promising lead structures in AD drug discovery and aims to guide future medicinal chemistry efforts toward more effective, disease-modifying therapies.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-enabled Antibiotic Discovery and Repurposing: Precision Strategies to Combat Antimicrobial Resistance.","authors":"Manish Pathak, Akansha Dwivedi","doi":"10.2174/0113895575477448260915102301","DOIUrl":"https://doi.org/10.2174/0113895575477448260915102301","url":null,"abstract":"<p><strong>Introduction: </strong>The effectiveness of some existing antibiotics is being compromised by the ever-rising rate at which antimicrobial resistance develops. Artificial Intelligence (AI) is one of the most significant technological innovations that have become possible through which chemical diversity can be explored, interactions between drugs and targets predicted, and novel compounds developed to address bacterial infections. This paper will discuss the role of artificial intelligence technology in antibiotic discovery.</p><p><strong>Methods: </strong>The capabilities of generative AI, deep learning, and machine learning to contribute to drug design, pharmacokinetic/pharmacodynamic property optimization, molecular screening, and prediction of mode of action were analyzed. Examples such as the discovery of halicin and peptide design using AI were also considered.</p><p><strong>Results: </strong>The advent of AI technology has made it possible to predict the activity and resistance mechanisms for antibiotics, as well as to create structurally diverse molecules. Multimodal data analysis, neural network docking, and reinforcement learning have helped in decreasing preclinical attrition.</p><p><strong>Discussion: </strong>Despite the huge promise offered by these technologies, several challenges must be overcome before these can be fully adopted. Issues such as low data quality, poor interpretability of the models, and regulatory requirements might slow down the implementation of AI technologies. Ethics and data formatting will be important determinants of the successful integration of AI technologies.</p><p><strong>Conclusion: </strong>AI represents an efficient and promising tool for antibiotic development through the integration of advanced computational techniques with empirical evaluation.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Isatin Derivatives as Multifunctional Antidiabetic Agents: Insights into α-Glucosidase and α-Amylase Inhibition.","authors":"Manami Sardar, Teasha Chakraborty, Prasenjit Mondal, Priya Das","doi":"10.2174/0113895575483401260915070007","DOIUrl":"https://doi.org/10.2174/0113895575483401260915070007","url":null,"abstract":"<p><p>Diabetes mellitus, especially Type 2 Diabetes (T2DM), appears to be a worldwide health challenge marked by progressing hyperglycemia and related complications. Postprandial Hyperglycemia (PPHG) is a critical therapeutic target due to its strong link with cardiovascular risks. Inhibition of carbohydrate-hydrolysing enzymes, α-glucosidase and α-amylase, is an established strategy to mitigate PPHG. Current Inhibitors, including acarbose, miglitol, and voglibose, are effective but limited by gastrointestinal side effects. Isatin (1H-indole-2,3-dione) is a privileged scaffold in medicinal chemistry with diverse biological activities and modifiable sites (N-1, C-3, C-5), enabling optimisation for enzyme inhibition. A comprehensive literature search was conducted up to December 2025 using databases including Google Scholar, Web of Science, PubMed, traditional integrated knowledge resources, local dissertations, and books. The search employed keywords such as \"α- glucosidase,\" \"type 2 diabetes,\" \"isatin scaffolds,\" \"standard α-glucosidase enzyme inhibitors,\" and \"isatin derivatives showing α-glucosidase and α-amylase inhibitory activity.\" This review compiles recent advances in isatin derivatives as potential α-glucosidase and α-amylase inhibitors, highlighting structure-activity relationships, synthetic strategies, including green chemistry and microwaveassisted synthesis, and dual inhibitory activity for improved efficacy and safety. Reported derivatives demonstrate remarkable potency, with some surpassing standard drugs in IC₅₀ values and docking scores, offering promising leads for next-generation antidiabetic therapeutics. Isatin derivatives show strong potential as multifunctional antidiabetic agents by effectively inhibiting α- glucosidase and α-amylase. Their structural versatility enables enhanced enzyme inhibition, supporting their promise as lead compounds for postprandial glucose control.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Natural Products in Ameliorating Mitochondrial Dysfunction in Diabetic Kidney Disease and the Underlying Mechanisms.","authors":"Yunzhou Wu, Junwei Gao, Jiazhen Lin, Jie Xing, Xudong Cai","doi":"10.2174/0113895575476248260922073914","DOIUrl":"https://doi.org/10.2174/0113895575476248260922073914","url":null,"abstract":"<p><p>Diabetic Kidney Disease (DKD), a prevalent microvascular complication of diabetes mellitus, represents the leading cause of end-stage renal disease worldwide. Its pathogenesis is multifactorial, involving metabolic disturbances, oxidative stress, inflammatory responses, and notably, mitochondrial dysfunction. Mitochondria, as the primary energy-producing organelles, undergo morphological and functional impairment under hyperglycemic conditions, including excessive reactive oxygen species generation, aberrant dynamics (fusion/fission imbalance), defective mitophagy, reduced biogenesis, and activation of mitochondria-mediated apoptosis. These interconnected abnormalities contribute to glomerular and tubular injury, ultimately promoting renal fibrosis and functional decline. Emerging evidence highlights the therapeutic potential of natural products-such as flavonoids, polyphenols, alkaloids, and saponins-in restoring mitochondrial homeostasis through multitarget mechanisms. These compounds activate the Nrf2/ARE and AMPK/SIRT1/PGC- 1α pathways to enhance antioxidant defense and promote mitochondrial biogenesis; regulate Drp1/Mfn1/2/OPA1 to restore mitochondrial dynamics; induce PINK1/Parkin- or BNIP3-mediated mitophagy to clear dysfunctional mitochondria; and modulate Bcl-2/Bax/caspase signaling to suppress apoptosis. Despite robust preclinical efficacy, clinical translation is hindered by poor bioavailability, batch-to-batch variability, lack of standardized formulations, and limited high-quality trials with mitochondrial-specific endpoints. Advances in kidney-targeted nanodelivery systems and AIdriven compound screening offer promising strategies to overcome these barriers. This review synthesizes current knowledge on the mechanisms by which natural products alleviate mitochondrial dysfunction in DKD, evaluates translational challenges, and proposes future directions for developing these compounds into adjunctive therapies.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Postbiotic to Prodrug: Chemical Strategies to Widen the Therapeutic Potential of Butyric Acid.","authors":"Bhupinder Kapoor, Monica Gulati","doi":"10.2174/0113895575503053260913151114","DOIUrl":"https://doi.org/10.2174/0113895575503053260913151114","url":null,"abstract":"<p><p>Postbiotics, particularly Short-Chain Fatty Acids (SCFAs), have recently emerged as safe and measurable alternatives to live probiotics. Postbiotics are metabolites produced through the gut microbial fermentation of dietary fibers and primarily comprise acetate, propionate, and butyrate, which together account for approximately 90% of the total SCFAs produced. Among these, butyrate has been the most extensively investigated because of its broad therapeutic potential in a wide range of gastrointestinal, neurological, cardiovascular, metabolic, and immunological disorders. The therapeutic effects of butyric acid are primarily attributed to the inhibition of Histone Deacetylase (HDAC) and activation of G Protein-Coupled Receptors (GPCRs), thereby modulating gene expression, immune responses, and intestinal barrier integrity. Despite its promising pharmacological profile, the clinical application of free butyric acid is limited by its unpleasant odor and taste, poor gastrointestinal stability, and rapid systemic metabolism. To overcome these limitations, various chemical modification strategies have been explored. Conjugation of the free carboxylic acid group of butyric acid with diverse promoieties, including fatty acids, amino acids, monosaccharides, polyhydric alcohols, and polymers, through esterification or amidation, has led to the development of several butyric acid prodrugs. These prodrugs undergo enzymatic hydrolysis, often mediated by pancreatic lipases, to release active butyrate in a controlled manner. Such modifications not only improve the organoleptic and pharmacokinetic properties of butyric acid but also, in some cases, enable sitespecific, sustained, and targeted drug delivery. Preclinical studies have demonstrated that butyrate prodrugs exhibit superior therapeutic efficacy compared with free butyric acid in various oncological, neuromuscular, cardiovascular, metabolic, and inflammatory disorders. Furthermore, formulation- based approaches, including nanoparticle-based delivery systems, have been employed to further enhance bioavailability and therapeutic performance. Notably, a few butyrate prodrugs, such as tributyrin and AN-9, are currently undergoing clinical evaluation, highlighting their translational potential. This review summarizes recent advances in the design and therapeutic applications of butyric acid prodrugs, with particular emphasis on their potential as next-generation postbiotic-based therapeutics.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}