Mini reviews in medicinal chemistry最新文献

{"title":"Dihydropyrimidines as Multifaceted Scaffolds: A Comprehensive Review of Synthetic Approaches and Biological Significance.","authors":"Prafulla Sabale, Priya Rahangdale, Deepti Verma, Vidya Sabale","doi":"10.2174/0113895575463631260903065552","DOIUrl":"https://doi.org/10.2174/0113895575463631260903065552","url":null,"abstract":"<p><p>Dihydropyrimidines (DHPMs) are an important class of heterocyclic compounds with broad pharmacological and therapeutic potential. Among the various synthetic routes for assembling the DHPM frame, the classical Biginelli reaction remains the most effective and widely used method due to its convenient one-pot procedure. Structurally, DHPMs offer valuable flexibility, enabling the incorporation of numerous functional groups to enhance pharmacological properties. This review highlights key pharmacological activities of DHPMs, including antihypertensive, anticancer, calcium channel-blocking, anti-inflammatory, antiviral, antitubercular, anticonvulsant, analgesic, antimicrobial, lipoxygenase inhibitory, xanthine oxidase inhibitory, and urease inhibitory effects, while focusing on recent developments in synthetic methods and structure-activity relationship (SAR) studies relevant to the advancement of therapeutically active molecules. The article further discusses how these diverse properties inspire the rational design and structural modification of new dihydropyrimidine derivatives to yield more effective, selective, and safer drug candidates for various clinical applications. This review underlines the dihydropyrimidine framework's biological significance and its advancing potential in therapeutic innovation and medicinal chemistry.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081500","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":"Neuroprotective Role of Flavonoids: Implications for Natural Epilepsy Therapy-A Systematic Review.","authors":"Vidhi Upadhyaya, Aanchal Loshali, Nidhi Tiwari, Preeti Badoni, Sushmita Uniyal, Aarti Sati, Bhuwan Chandra Joshi","doi":"10.2174/0113895575470858260827060917","DOIUrl":"https://doi.org/10.2174/0113895575470858260827060917","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Epilepsy is a chronic neurological disorder characterised by recurrent, unprovoked seizures due to abnormal neuronal hyperexcitability and dysfunction. Despite the availability of several Antiepileptic Drugs (AEDs), approximately one-third of epilepsy patients are drugresistant and often experience adverse effects. This has led to the search for plant- derived bioactive compounds such as flavonoids, which have been reported to have widespread neuroprotective effects. This study aims to evaluate the neuroprotective role of flavonoids and their therapeutic implications in the management of epilepsy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;A systematic literature search was conducted on electronic databases such as PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar with PRISMA guidelines. Relevant literature on the neuroprotective effects of flavonoids and their applications in epilepsy was reviewed. Both in vitro and in vivo studies on the anticonvulsant and neuroprotective effects of flavonoids in chemically and electrically induced epilepsy models were analyzed to obtain relevant information on the mechanisms of action and molecular targets of flavonoids, frequency of seizures, neurobehavioral effects, and histopathological effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The studies clearly demonstrate that flavonoids exert anticonvulsant and neuroprotective effects through multiple mechanisms. These include reducing oxidative stress by enhancing endogenous antioxidant enzymes, suppressing pro-inflammatory cytokines, modulating GABAergic and glutamatergic neurotransmission, inhibiting voltage-gated ion channels, stabilising mitochondrial function, and decreasing apoptotic signalling. Several studies report decreased seizure severity, increased seizure latency, and preservation of hippocampal neuronal integrity following flavonoid administration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;According to the data compiled in this review, flavonoids have broad-spectrum neuroprotective effects by modulating several molecular targets linked to epileptogenesis. This multitargeted profile may provide benefits above traditional therapies and is consistent with the intricate biology of epilepsy. However, there is little translational and clinical confirmation in the present body of evidence, which is primarily preclinical. Variations hamper standardization and limit comparative analysis of flavonoid content, dosage regimens, and experimental design. Further research is required to establish therapeutic usefulness, particularly regarding bioavailability, pharmacokinetics, and possible drug- herb interactions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Flavonoids demonstrate significant multi-target neuroprotective potential in experimental models of epilepsy. This article focuses on various aspects, such as the mechanisms of action and neuroprotective benefits of various flavonoids against epilepsy. The article highlights the ","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039327","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":"Coumarin-pyrazole Hybrids as Potential Anticancer Agents: A Mini-review of Developments in Medicinal Chemistry.","authors":"Guangqiang Bai, Xing Huang, Yong He","doi":"10.2174/0113895575507235260909084032","DOIUrl":"https://doi.org/10.2174/0113895575507235260909084032","url":null,"abstract":"<p><p>Coumarins and pyrazoles are two essential heterocyclic scaffolds in medicinal chemistry, which are extensively applied in the drug discovery and development process owing to their various biological activities. Through the molecular heterocyclic strategy to construct coumarin-pyrazole hybrid heterocyclic molecules, the pharmacokinetic and pharmacodynamic characteristics of the parent compounds can be effectively optimized. According to the structural connection modes, these heterocyclic compounds can be categorized into three main types: fused type, condensed type, and heterocyclic type linked by connecting groups. Among these categories, the condensed type and the linked type can be further subdivided according to the connection positions on the coumarin skeleton, such as derivatives substituted at the C3, C4, C6, C7, and C8 positions. This review summarizes the biological activities, structure-activity relationships (SAR), and action mechanisms of different types of coumarin-pyrazole heterocyclic compounds, intending to provide a reference for the design of novel drugs based on this heterocyclic framework.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038856","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":"Novel Stimuli-Responsive Gel Systems for Improved Localized Therapy of Cervical Cancer.","authors":"Amit Pratap SIngh, Sushil Kumar Kashaw, Vandana Soni","doi":"10.2174/0113895575478425260828051124","DOIUrl":"https://doi.org/10.2174/0113895575478425260828051124","url":null,"abstract":"<p><p>Cervical cancer remains a significant global health concern among women. Conventional treatments including surgery, often lead to complications that may compromise future fertility and childbirth outcomes, particularly in younger patients. Owing to its large surface area and rich vascularization, the vaginal route offers promising pathway for localized drug delivery. Nevertheless, the continual turnover of vaginal mucus presents major limitation for traditional formulations such as creams, gels, suppositories, and patches, reducing their retention and overall efficacy. In situ gelling drug delivery systems have emerged promising alternative, offering distinct benefits such as enhanced mucosal penetration, superior bioadhesion, site-specific and sustained drug release, and minimized systemic toxicity. These formulations remain in liquid form at ambient temperature but rapidly transform into gels upon exposure to physiological stimuli, including changes in temperature, pH, or light. By facilitating direct drug delivery to the target site, this route enables lower dosage requirements, minimizes adverse effects, and enhances therapeutic efficiency. This review highlights the application of in-situ gelling systems via the vaginal route for cervical cancer treatment. Moreover, this strategy may complement fertility-preserving surgical interventions by promoting preoperative tumor reduction, thereby decreasing the risk of premature birth and improving reproductive outcomes and quality of life in younger women.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039278","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 the Therapeutic Potential of Psilocybin: A Comprehensive Review of Clinical Trial Evidence and Implications for Rescheduling.","authors":"Fatemeh Abolhasani, Hojjat Rezaiezadeh, Mohammad Amin Langarizadeh, Marziye Ranjbar Tavakoli, Mehran Ilaghi, Parnian Zare, Faezeh Karbakhsh Ravari, Fatemeh Alamdar, Mohammad Banazadeh, Mohammad Shabani","doi":"10.2174/0113895575443239260828094859","DOIUrl":"https://doi.org/10.2174/0113895575443239260828094859","url":null,"abstract":"<p><p>Psilocybin, a compound found in certain species of Psilocybe mushrooms, shows potential as a treatment for various psychiatric conditions. In the past decade, a growing body of evidence has shown the effectiveness of psilocybin in treating conditions, such as treatment-resistant depression, generalized anxiety disorder, post-traumatic stress disorder, and substance use disorders. This review provides a thorough overview of clinical and neurobiological studies investigating psilocybin's biological pathways and therapeutic outcomes. Psilocybin primarily acts as a serotonin 2A receptor agonist, modulating cortical and limbic networks involved in emotional regulation, neural plasticity, and cognitive flexibility. Controlled clinical trials have demonstrated that psilocybin, when administered under structured psychotherapeutic supervision, leads to significant changes in perception and self-awareness, resulting in lasting improvements in mood, emotional well-being, and overall quality of life. Reported side effects are generally mild and self-limiting, such as nausea, nervousness, and headaches, indicating a favorable safety profile. However, further research remains essential to optimize dosing protocols, assess long-term safety and effectiveness, and explore its broader clinical applicability. Additionally, if psilocybin were to be reclassified from a Schedule I substance, pending adequate regulatory approval and strong scientific evidence, it could represent a significant shift in psychiatric treatment, offering an innovative, mechanism-based therapeutic option for individuals who do not respond adequately to standard drug therapies.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017245","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":"Multifunctional Therapeutic Potential of Corynoline: A Benzophenanthridine derived Alkaloid.","authors":"Navin Kumar Tailor","doi":"10.2174/0113895575504120260831180535","DOIUrl":"https://doi.org/10.2174/0113895575504120260831180535","url":null,"abstract":"<p><p>Corynoline is a naturally occurring benzophenanthridine-derived alkaloid widely isolated from plants of the genus Corydalis, which have been used for centuries in traditional herbal medicine for the management of inflammation, pain, and infectious diseases. Belonging to the structurally unique benzophenanthridine class, corynoline possesses a distinctive chemical scaffold that underlies its diverse and potent biological interactions. In recent years, a growing body of experimental studies has demonstrated that corynoline exhibits a remarkably wide range of pharmacological activities, including anti-inflammatory, anticancer, neuroprotective, hepatoprotective, cardioprotective, anti-osteoporotic, and renal ischemia-reperfusion protective effects. These multifaceted activities are mediated through the modulation of several cellular signaling pathways, including Nrf2/HO-1, MAPKs, NF-κB, NOS3, AKT/GSK3β/Nrf2, STAT3/Bcl-2, and Src/JNK, highlighting its capacity to simultaneously target multiple disease-relevant molecular networks. This review aims to comprehensively summarize current knowledge regarding the chemical characteristics, pharmacological activities, underlying molecular mechanisms, and therapeutic prospects of corynoline. Despite its promising pharmacological profile, the clinical translation of corynoline remains hindered by insufficient pharmacokinetic data, limited bioavailability studies, and inadequate toxicity evaluations. Therefore, further rigorous preclinical and clinical investigations are warranted to fully elucidate its safety profile, therapeutic efficacy, and drug-like properties. By integrating mechanistic insights with translational perspectives, this article seeks to stimulate future research aimed at harnessing corynoline's unique chemical scaffold for the development of innovative and effective therapeutic strategies across multiple disease domains.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016401","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":"Benzoxanthone Derivatives as Emerging Therapeutic Agents: A Comprehensive Review.","authors":"Jon Jyoti Sahariah, Aparoop Das, Kalyani Pathak, Urvashee Gogoi, Manisha Sahariah, Saptasikha Gogoi","doi":"10.2174/0113895575491607260828102537","DOIUrl":"https://doi.org/10.2174/0113895575491607260828102537","url":null,"abstract":"<p><p>Benzoxanthone derivatives represent an important subclass of xanthone-based heterocyclic compounds that have attracted increasing scientific attention due to their diverse structural features and wide range of reported biological activities. This review compiles and critically summarizes published literature on the sources, chemical synthesis, structural modifications, and pharmacological properties of benzoxanthone derivatives. Emphasis is placed on documented structureactivity relationships, highlighting the influence of ring fusion, substituent pattern, and extended π- conjugation on biological responses. Reported experimental findings from in silico, in vitro, and in vivo studies demonstrating anticancer, antimicrobial, antioxidant, anti-inflammatory, and enzyme inhibitory activities are discussed based on available evidence. The review also outlines current synthetic strategies and analytical approaches used to characterize benzoxanthone compounds, along with reported limitations in solubility, bioavailability, and toxicity assessment. By presenting consolidated factual information from existing studies, this article aims to provide a comprehensive reference for researchers and to support further systematic investigation of benzoxanthone derivatives in medicinal and pharmaceutical research.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017275","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":"Combination Therapy of Salbutamol and Spirulina: A Novel Dual-Action Approach for Asthma Management.","authors":"Vaishali Tyagi, Charu Saxena","doi":"10.2174/0113895575478652260830064518","DOIUrl":"https://doi.org/10.2174/0113895575478652260830064518","url":null,"abstract":"<p><p>Asthma is a chronic inflammatory respiratory disorder characterized by airway hyperresponsiveness, oxidative stress, and recurrent bronchoconstriction. Conventional treatment with β2- agonists such as salbutamol provides rapid symptomatic relief through bronchodilation; however, it does not adequately address the underlying inflammation and oxidative damage associated with disease progression. Spirulina, a nutrient-rich cyanobacterium, possesses significant antioxidant, antiinflammatory, and immunomodulatory properties that may complement the pharmacological effects of salbutamol. This review explores the potential of combining salbutamol and spirulina as a novel dual-acting therapeutic strategy for asthma management. The proposed synergistic mechanism involves immediate bronchodilation mediated through β2-adrenergic receptor stimulation by salbutamol, alongside spirulina-mediated modulation of inflammatory cytokines, inhibition of eosinophilic infiltration, and reduction of oxidative stress. Preclinical findings and limited clinical evidence suggest that spirulina supplementation may improve pulmonary function and decrease inflammatory biomarkers in individuals with asthma. In addition, the review discusses formulation and delivery considerations that may influence the therapeutic effectiveness of this combination approach. Although preliminary evidence supports the potential benefits of combining pharmacological and nutraceutical interventions, large-scale randomized clinical trials are required to establish efficacy, optimize dosing strategies, and evaluate long-term safety. Overall, the integration of spirulina with salbutamol may represent a promising adjunctive strategy and a potential paradigm shift in comprehensive asthma management.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017322","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":"Potential Diagnostic and Therapeutic Role of Amino Acids in Diabetic Kidney Disease: An Updated Review.","authors":"Shalini K Sawhney, Anandi Kapri","doi":"10.2174/0113895575473234260830070124","DOIUrl":"https://doi.org/10.2174/0113895575473234260830070124","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Amino acids play a crucial role in both the diagnosis and treatment of DKD. This review examines the mechanism by which amino acids exert their biological effects and their relevance to the diagnosis and management of DKD.</p><p><strong>Methods: </strong>A literature search was conducted using PubMed, Scopus, and Web of Science. Search terms included \"DKD\", \"Type 2 Diabetes Mellitus (T2DM)\", \"Blood Pressure (B.P)\", \"Proteinuria\", \"microalbuminuria\", \"Inflammatory cytokines\", \"homocysteine\", \"nephrotoxicity\", and \"amino acids\" used to identify relevant studies. Several studies demonstrated that amino acid supplementation attenuates serum transforming growth factor-β (TGF- β) levels and the urinary albumin- to-creatinine ratio, and improves metabolic parameters in patients with T2DM. Improvements in kidney function and B.P were also observed, suggesting that amino acid supplementation may prevent the progression of microalbuminuria. Patients with DKD exhibit altered levels of inflammatory cytokines and homocysteine. In some studies, combination therapy was more effective in reducing nephrotoxicity.</p><p><strong>Results: </strong>Metabolomics profiling of urinary and serum metabolic pathways has emerged as a promising approach for identifying potential diagnostic biomarkers in patients with DKD. Candidate biomarkers include tryptophan, threonine, citrulline, methionine and homovanillic acid sulphate. Abnormal amino acid metabolism in DKD is associated with oxidative stress, inflammatory and immune dysregulation, mitochondrial dysfunction, iron death and dysregulated autophagy.</p><p><strong>Discussion: </strong>Drugs that interrupt the renin-angiotensin- aldosterone system can help control these changes. Abnormal amino acid metabolism in DKD is closely linked to oxidative stress, inflammatory responses and immune responses, as well as mitochondrial dysfunction, iron death and impaired autophagy.</p><p><strong>Conclusion: </strong>Altered amino acid profiles in DKD may serve as early diagnostic markers. Metabolomic approaches enable detection of changes in non-essential amino acids and early kidney damage before the onset of proteinuria, reflecting changes in the local renal microenvironment that precede clinically detectable proteinuria.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016924","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":"Designing Multi-functional Antioxidants for Neurodegenerative Disorders.","authors":"Kuleshwar Sahu, Rakesh Sahu, Mahima Mishra, Nikita Chhabra, Sophiya Tiwari, Kamalpreet Kaur, Hemlata Rathore, Rajkumari Lodhi, Kunjbihari Sulakhiya","doi":"10.2174/0113895575494157260901095536","DOIUrl":"https://doi.org/10.2174/0113895575494157260901095536","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDs), including Alzheimer's disease, Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD) and Multiple Sclerosis (MS), pose a major global health threat due to complex pathology, increased prevalence, and lack of effective therapies. Numerous findings have indicated that oxidative stress (OS) is a central and unifying pathological mechanism driving neuronal dysfunction and degeneration across these disorders. Excessive reactive oxygen species (ROS) and nitrogen species (RNS) generation, coupled with impaired endogenous antioxidant defenses, leads to lipid peroxidation, protein misfolding, nucleic acid damage, mitochondrial dysfunction, neuroinflammation, metal dyshomeostasis, and disruption of the blood-brain barrier (BBB). These interconnected processes form self-perpetuating pathogenic cycles that accelerate synaptic failure and neuronal loss. This review is a compilation of thoroughly searched literature from the last 20 years (2006-2026) on OS-mediated neurodegeneration and emerging antioxidant-based therapeutic strategies for neurodegenerative disorders, sourced from PubMed, Scopus, ScienceDirect, Google Scholar, and Web of Science. Relevant articles were selected using specific keywords \"Neurodegenerative Disorders\", Neurodegenerative disorders and antioxidants\", \"Alzheimer's Disease and Oxidative Stress\", \"Parkinson's Disease and Oxidative Stress\", \"Alzheimer's Disease and Multi-functional Antioxidants\", \"Parkinson's Disease and Multifunctional Antioxidants\", \"Neurodegenerative Disorders and Antioxidant therapies\". Despite strong mechanistic support, conventional antioxidant-based therapies have demonstrated limited clinical success, largely due to poor bioavailability, inadequate BBB penetration, and failure to address the multifactorial nature of neurodegeneration. Consequently, there is a paradigm shift toward the development of multi-functional antioxidants capable of simultaneously targeting multiple redoxdriven pathways. Such agents are designed to combine free-radical scavenging, metal chelation, mitochondrial protection, modulation of redox-sensitive signaling pathways, and regulation of neuroinflammatory responses within a single therapeutic framework. By restoring redox homeostasis while preserving physiological redox signaling, multi-functional antioxidants offer a rational and promising disease-modifying strategy. This review critically examines OS-mediated mechanisms underlying major NDs and emphasizes the therapeutic potential of designed multi-functional antioxidants as next-generation neuroprotective agents.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017270","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}