Central nervous system agents in medicinal chemistry最新文献

{"title":"MAO-B Inhibitory and Antioxidant Properties of Flavonoids from Chenopodium album: Implications for Neuroprotection.","authors":"Teenu Pal, Prabhat Singh","doi":"10.2174/0118715249481290260916055723","DOIUrl":"https://doi.org/10.2174/0118715249481290260916055723","url":null,"abstract":"<p><strong>Introduction: </strong>Neurodegenerative diseases, especially Parkinson's disease, have been linked with oxidative stress, mitochondrial malfunction, neuroinflammation, and dopamine metabolism impairment. On the other hand, C. album is a medicinal plant containing high concentrations of flavonoids, which provide neuroprotective potential by acting as antioxidants and MAO-B inhibitors.</p><p><strong>Methods: </strong>In this review, scientific data obtained by various approaches such as phytochemical screening, in vitro, in vivo, and computational analysis about significant flavonoids of C. album (e.g., quercetin, kaempferol, spinacetin) were collected. Characteristics, methods for identification, and biological activity were reviewed concerning their neuroprotective action.</p><p><strong>Results: </strong>Flavonoids present in C. album exhibited potent scavenging of free radicals, improved intrinsic defense systems, decreased lipid peroxidation, and maintenance of mitochondrial health. Quercetin and kaempferol exhibited remarkable inhibition of MAO-B activity, where as spinacetin analogs provided supplementary antioxidants and anti-inflammatory activities. Studies demonstrated lower levels of reactive oxygen species production, increased neuronal survival, decreased neuronal death, and favorable motor performance.</p><p><strong>Discussion: </strong>The multitarget effect of C. album flavonoids becomes especially important when considering degenerative nervous system disorders because a monotherapeutic approach cannot be effective in such cases. The simultaneous influence on oxidative stress, inflammation, apoptosis, and dopamine oxidation can help preserve dopaminergic neurons.</p><p><strong>Conclusion: </strong>The flavonoids from Chenopodium album have shown great potential as a neuroprotective agent. Still, further study is required before it can be used to treat any neurodegenerative condition in the clinical setting.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into the Neuroprotective Potential of Luteolin: An Overview.","authors":"N Ramalakshmi, S Dibenthiran, S Arunkumar, S Amuthalakshmi, S Indrakumar, C N Nalini","doi":"10.2174/0118715249434117260910074306","DOIUrl":"https://doi.org/10.2174/0118715249434117260910074306","url":null,"abstract":"<p><p>Neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, are characterized by pathologies such as oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein aggregation. Luteolin, a natural flavonoid, is known for its neuroprotective properties, targeting key pathological mechanisms. This review highlights the multi-target effects of luteolin, as demonstrated by in vitro and in vivo studies. Luteolin reduces oxidative damage by scavenging ROS, enhancing antioxidant enzymes, such as SOD, CAT, and GPx, and activating the Nrf2/ARE pathway. It reduces neuroinflammation by inhibiting NF-κB, AP-1, and JNK signalling and by lowering pro-inflammatory cytokines such as TNF-α and IL-1β. Luteolin maintains mitochondrial membrane potential, modulates apoptotic pathways via Bcl-2/Bax and PI3K/Akt signalling, and promotes autophagy by upregulating LC3-II and modulating the p62-Keap1-Nrf2 axis. It disrupts amyloidogenic and tau hyperphosphorylation pathways, inhibits AChE activity, enhances cholinergic transmission, and improves cognitive function by upregulating CREB, BDNF, and synaptic proteins. Although promising, these effects have been observed mainly in preclinical models, with limited clinical evidence. Future research should focus on the clinical validation and improvement of delivery systems to enhance brain bioavailability. This review provides a foundation for the development of luteolin as a therapeutic candidate for neurodegenerative diseases.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Profile of Dexpanthenol in Traumatic Spinal Cord Injury: A Focus on the Inhibition of Ferroptotic Cell Death.","authors":"İlçim Ermutlu, Şerife Efsun Antmen, Tolga Akbiyik, Hamide Sayar","doi":"10.2174/0118715249476221260930032152","DOIUrl":"https://doi.org/10.2174/0118715249476221260930032152","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Traumatic spinal cord injury (TSCI) is a catastrophic insult to the central nervous system (CNS) and often leaves patients with profound, long-term neurological disability. In this study, we evaluated whether dexpanthenol, a vitamin B5 precursor, exerts neuroprotective effects in a rat model of TSCI. We also sought to clarify the mechanisms that might account for any observed benefit, focusing on pathways related to apoptosis, inflammation, oxidative stress, and ferroptosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used Wistar albino rats and allocated them into four groups: Control, Sham, Trauma, and Dexpanthenol. Animals in the sham group underwent laminectomy alone. In contrast, rats in the trauma and dexpanthenol groups received a standardized contusion injury created by dropping a 10 g weight from 10 cm onto the exposed spinal cord. Immediately after injury, we administered dexpanthenol intraperitoneally (i.p.) to the treatment group. Neurological function was evaluated 24 h later using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Biochemical analyses were performed on tissue samples to measure markers of apoptosis (Caspase-3), inflammation (Myeloperoxidase, MPO), lipid peroxidation (Malondialdehyde, MDA), oxidative stress (Xanthine Oxidase, XO, Catalase, CAT), and ferroptosis (Glutathione, GSH, Glutathione Peroxidase 4, GPX4, Acyl-CoA Synthetase Long Chain Family Member 4, ACSL4, and Solute Carrier Family 7 Member 11, SLC7A11). Moreover, we prepared hematoxylin and eosin (H&E) stained sections and carried out a semi-quantitative histopathological evaluation based on these slides.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Relative to the sham condition, spinal cord contusion produced a clear functional deterioration, with BBB locomotor scores dropping sharply and histopathological injury becoming more pronounced. In parallel, the trauma group showed substantial biochemical increases in caspase-3, MPO, MDA, XO, and ACSL4. In contrast, antioxidant and ferroptosis-related defenses were suppressed after injury, as reflected by significantly lower CAT, GSH, GPX4, and SLC7A11 levels. Administration of dexpanthenol shifted this profile. Animals receiving treatment performed better on the BBB scale than untreated trauma rats, indicating a significant recovery of neurological function. Consistently, tissue damage on histology was attenuated, pro-apoptotic and pro-oxidant markers (caspase-3, MPO, MDA, XO, and ACSL4) were reduced, and the depleted protective factors (CAT, GSH, GPX4, and SLC7A11) were brought back toward baseline in a statistically significant manner.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The restoration of antioxidant defenses and the specific inhibition of lipid peroxidation markers suggest that dexpanthenol's efficacy extends beyond general anti-inflammatory effects. By targeting ferroptosis-associated molecular changes via the preservation of the GPX4/GSH axis, dexpanthenol addresses a fundamental m","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effect of Imeglimin Hydrochloride on H2O2-Induced SH-SY5Y Cells.","authors":"Priyanjanaa Chandrasekar, Jai Akash Kishore Kumar, Chitra Vellapandian, Krishna Prabha Naduchamy","doi":"10.2174/0118715249512928260918130405","DOIUrl":"https://doi.org/10.2174/0118715249512928260918130405","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease is characterized by cognitive decline accompanied by the degeneration of cholinergic neurons. Notably, ROS make neurons more vulnerable to oxidative stress-induced damage and functional impairment in the brain. Hence, this research aimed to explore the antioxidant and neuroprotective activities of Imeglimin HCl in the SH-SY5Y cell line.</p><p><strong>Methods: </strong>Initially, the cytotoxic effect of Imeglimin HCl at 6.25 and 12.5 μg/mL was determined using the MTT assay. Subsequently, the inhibitory effect of Imeglimin HCl on H2O2-induced Reactive Oxygen Species (ROS) in SH-SY5Y cells was carried out.</p><p><strong>Results: </strong>The study demonstrated that 70% of cells were viable up to 12.5 μg/mL. The ROS inhibition assay showed that Imeglimin HCl inhibited the H2O2-induced ROS production in SH-SY5Y cells. It was concluded from the study that Imeglimin HCl has a neuroprotective effect.</p><p><strong>Discussion: </strong>In SH-SY5Y cells, HⁿOⁿ exposure mimics AD-related oxidative damage by elevating ROS and impairing mitochondrial function. Excessive ROS generation induced by H2O2 compromises mitochondrial membrane stability, which in turn activates the intrinsic apoptotic pathway. In the present study, Imeglimin hydrochloride significantly attenuated HⁿOⁿ-induced ROS generation, indicating a protective effect against oxidative stress.</p><p><strong>Conclusion: </strong>It was concluded from the study that Imeglimin hydrochloride acts on GABA-A and M2 Muscarinic acetylcholine receptors, which play a prominent role in AD, since it has a better binding affinity. In addition, Imeglimin HCl exhibited antioxidant properties in SH-SY5Y cell lines by reducing reactive oxygen species production.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Understanding of TBI Injury: Pathophysiological Mechanism, Secondary Damage, and Emerging Neuroprotective Strategies.","authors":"Preet Bhadana, Hitesh, Sunishtha Kalra","doi":"10.2174/0118715249480900260920063703","DOIUrl":"https://doi.org/10.2174/0118715249480900260920063703","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is among the leading causes of mortality and long-term disability worldwide, particularly in younger populations. Despite extensive research, there are currently no clinically effective neuroprotective therapies capable of fully preventing secondary neurological damage after TBI. The pathological progression of TBI involves both primary and secondary injury mechanisms. Primary injury occurs immediately after mechanical trauma and results in irreversible structural damage, whereas secondary injury develops progressively over hours to days and significantly contributes to neuronal degeneration and neurological dysfunction. Secondary injury cascades include excitotoxicity, oxidative stress, mitochondrial dysfunction, blood-brain barrier (BBB) disruption, cerebral edema, neuroinflammation, calcium overload, and apoptotic cell death. These interconnected mechanisms aggravate tissue injury and impair cognitive, behavioural, and motor functions. Experimental animal models have substantially improved the understanding of TBI pathophysiology and facilitated the development of potential therapeutic approaches; however, successful translation from experimental studies to clinical application remains limited. Recent advances in molecular diagnostics have identified extracellular vesicles, microRNAs, and other circulating biomarkers as promising tools for early diagnosis and prognosis. In addition, growing interest has emerged in natural and herbal neuroprotective compounds because of their antioxidant and anti-inflammatory properties. This review comprehensively discusses the major pathophysiological mechanisms underlying TBI, translational limitations of current therapeutic strategies, and future directions for developing effective multimodal neuroprotective interventions.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Insights on CNS-Targeted Matrix Metalloproteinase Inhibitors for the Management of Alzheimer's Disease.","authors":"Sumit Kumar, Jagrati Kumari, Damodara Naidu Kommi, Gopal L Khatik","doi":"10.2174/0118715249471785260829144035","DOIUrl":"https://doi.org/10.2174/0118715249471785260829144035","url":null,"abstract":"<p><p>Matrix metalloproteinases, or MMPs, are enzymes that depend on zinc and play a key role in remodelling the extracellular matrix as well as regulating neuroinflammation within the central nervous system. There's growing evidence that when MMP activity is imbalanced, it contributes to the development of Alzheimer's disease. Interestingly, these enzymes are involved in beneficial and harmful processes such as amyloid-β (Aβ) destruction, disrupting the blood-brain barrier, and fuelling neuroinflammation. This review focused on the recent progress made between 2015 and 2025 in understanding the role of MMPs in Alzheimer's disease, especially focusing on their complexity. We also included key studies published before 2015 to give a basic understanding of MMP biology. The search strategy employed a combination of keywords and Boolean operators, including \"Alzheimer's disease,\" \"matrix metalloproteinase,\" and \"MMP inhibitor,\" used both independently and in various combinations to maximize retrieval sensitivity. To gather the information, a thorough search was carried out using the PubMed database, and studies were selected based on relevance, quality of their methods, and potential to be applied in real-world settings. Following this rigorous screening and eligibility assessment process, approximately 85 articles were selected for detailed qualitative analysis. We analyzed the roles of key MMPs, such as MMP-2, MMP-9, MMP-3, and the membrane-type MMPs, with inconsistencies found across different studies to explore possible issues. Additionally, we also provide an overview of the latest progress in developing both natural and synthetic MMP inhibitors, paying special attention to how they work and their potential as therapies. This review highlights some of the key challenges that are retarding clinical progress, such as the lack of target selectivity, unwanted off-target activity, and the difficulty in crossing the blood-brain barrier. We also discussed promising new approaches, including selective inhibition, designing drugs with multiple functions, and advanced methods for delivering treatments to the central nervous system. Overall, MMPs are promising but quite complex targets when it comes to treating Alzheimer's disease. For translational research, it's crucial to gain a deeper understanding of how these enzymes work in different contexts and to develop selective inhibitors that can effectively reach the brain.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Biological Mechanisms in MDD Pathophysiology: Emerging Roles of Glymphatic Dysfunction, Ferroptosis, and Extracellular Vesicles (EVs).","authors":"Anjali Anand, Payal Mittal","doi":"10.2174/0118715249465563260901043608","DOIUrl":"https://doi.org/10.2174/0118715249465563260901043608","url":null,"abstract":"<p><p>Major Depressive Disorder (MDD) is one of the world's most disabling conditions. The traditional model focuses on monoaminergic imbalance, neurotrophic deficits, and hypothalamic- pituitary-adrenal (HPA) axis dysfunction. However, this model does not fully account for the complex symptoms and treatment resistance observed in MDD. Recent research highlights new biological mechanisms: glymphatic dysfunction, ferroptosis, and Extracellular vesicles (EVs) signaling. These findings mark a significant shift in understanding MDD pathophysiology. This study systematically reviewed literature from PubMed, Scopus, and Web of Science (2018-2025). It identified 71 eligible studies with preclinical and clinical findings. Evidence shows that impaired glymphatic clearance disrupts the exchange between cerebrospinal fluid and the brain's interstitial fluid. A loss of aquaporin-4 (AQP4) polarization drives this disruption. The result is neuroinflammation, oxidative stress, and disturbed sleep. Ferroptosis is a type of iron-dependent cell death marked by lipid peroxidation and glutathione depletion. It reduces neuronal viability and plasticity in brain regions involved in mood regulation. This aggravates MDD. Meanwhile, changes in EV microRNA, proteins, and lipids affect neuroinflammatory signaling and synaptic integrity. These changes act both as mediators and biomarkers of disease progression. The interaction between these pathways increases oxidative stress, neuroinflammation, and synaptic dysfunction. Together, they constitute an interconnected pathophysiological framework of MDD biology. Therapeutic options include promoting glymphatic flow through sleep regulation, using ferroptosis inhibitors and antioxidants, and developing EV-based diagnostics and therapies. These mechanisms suggest MDD pathophysiology involves impaired glymphatic clearance, oxidative imbalance, and disrupted intercellular communication. They offer potential targets for mechanism-based, personalized treatment strategies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Single-Target Approach: Polypharmacology and Multi-Target Therapeutics in Alzheimer's Disease.","authors":"Renu Yadav, Jyoti Sinha, Km Deeksha","doi":"10.2174/0118715249497051260829094309","DOIUrl":"https://doi.org/10.2174/0118715249497051260829094309","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-beta aggregation, tau pathology, oxidative stress, neuroinflammation, mitochondrial dysfunction, and synaptic degeneration. The limited clinical success of traditional single-target therapeutic approaches has highlighted the need for more comprehensive treatment strategies. Polypharmacology has emerged as a promising paradigm that seeks to simultaneously modulate multiple pathological pathways involved in disease progression. In particular, multi-target-directed ligands (MTDLs) have gained considerable attention due to their ability to integrate multiple pharmacological activities within a single molecular entity. This review summarizes current advances in polypharmacology-based approaches for Alzheimer's disease, including rational drug design, ligand-based and network pharmacology strategies, artificial intelligence-assisted drug discovery, and emerging multi-target therapeutics. Representative synthetic and natural-productderived MTDLs are critically evaluated with respect to their mechanisms of action, pharmacokinetic limitations, blood-brain barrier penetration, and clinical development status. Finally, major translational challenges and future opportunities are discussed. Collectively, polypharmacology represents a promising framework for developing next-generation disease-modifying therapies for Alzheimer's disease, although significant challenges remain before widespread clinical implementation can be achieved.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Green-Synthesized Curcumin-Coated Silver Nanoparticles on the Hippocampal Tissue in Chlorpyrifos-Exposed Developing Male Rats.","authors":"Amirhossein Rakhshanifard, Saeed Samarghandian, Mehdi Shakibaie, Shahnaz Rajabi, Behzad Mesbahzadeh, Alia Mohaqeq, Tahereh Farkhondeh","doi":"10.2174/0118715249421329260806034835","DOIUrl":"https://doi.org/10.2174/0118715249421329260806034835","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Pubertal modifications are likely to affect various regions of the central nervous system (CNS) structure and functioning by multiple mechanisms. The development of the CNS during this period makes this system highly susceptible to environmental pollutants and other toxic agents and drugs. Chlorpyrifos (CPF) is an organophosphate pesticide with well-known neurotoxic effects. It was found that natural antioxidant supplementation could ameliorate CPF-induced CNS damage. There is strong evidence regarding the protective effects of curcumin against CPF toxicity. Numerous attempts have been performed to potentiate the bioavailability of curcumin, including formulations with nanoparticles. Silver nanoparticles (AgNPs) are broadly applied in biomedicine due to their exceptional physicochemical characteristics. Nonetheless, several issues remain about their safety and efficacy, specifically in the nervous system, according to recent literature from 2022-2025. Therefore, this study aimed to investigate the effects of curcumin-coated silver nanoparticles on the hippocampus of CPF-exposed and non-exposed rats during the puberty stage.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;In this experimental study, 42 male Wistar rats aged 30 days were randomly divided into 7 groups, including control, oil, and CPF (5 mg/kg) groups, as well as four groups receiving curcumin-coated green silver nanoparticles (CUR-AgNPs) at doses of 40 and 80 μg/kg, both with and without CPF administration. After 30 days, all rats were anesthetized, and blood and hippocampal samples were collected to measure biochemical parameters including acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO), and subjected to histopathological examination.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;Significant changes were observed in the levels of tissue and serum AChE activity, as well as tissue MDA, among the CPF group compared with the control group (P&lt;0.001). However, no statistically significant differences were found in the mean levels of tissue NO and SOD between the two groups. CUR-AgNPs did not exhibit any change in the serum AChE activity and also in the mean tissue levels of MDA, NO, and SOD, as well as histopathological findings in the CPF-exposed group compared with the non-treated CPF-exposed group. However, histopathological examination indicated the incidence of necrotic neurons and severe eosinophilic cytoplasmic contraction in the CPF, CPF+ CUR-AgNPs and CUR-AgNPs groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Curcumin, as a potent antioxidant, could prevent AgNPs-induced oxidative stress; however, it was not able to prevent the accumulation and direct toxic effect of AgNPs in the neurons and resulted in direct toxic damage in the tissue through disruption of calcium homeostasis and mitochondrial dysfunction. Future studies are needed to determine the exact mechanisms involved in the direct toxic effect of CUR-AgNPs in the variou","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcone-Arylpiperazine Hybrids as Potential Antianxiety Agents: Synthesis, Biological Evaluation, Molecular Modeling, and Network Pharmacology Studies.","authors":"Sushil Kumar, Malavika Puthanveetil Sureshbabu, Nitin Sati, Akhlesh Kumari, Jatin Kishore Sharma","doi":"10.2174/0118715249421795251208222103","DOIUrl":"https://doi.org/10.2174/0118715249421795251208222103","url":null,"abstract":"<p><strong>Introduction: </strong>Anxiety disorders are among the most prevalent mental health conditions, yet recent drug development has yielded few novel antianxiety agents. This study explores chalcone- arylpiperazine hybrids as potential scaffolds for anxiolytic activity through a combination of synthesis, computational modeling, and preliminary behavioral evaluation.</p><p><strong>Materials and methods: </strong>Five chalcone-arylpiperazine hybrids (m_01 to m_05) were synthesized via condensation of 1-[4-(3-chloropropoxy)-phenyl]-3-phenyl-prop-2-en-1-one with various substituted phenylpiperazines. Molecular docking was performed using AutoDock with the human GABAA receptor (PDB 4COF), followed by molecular dynamics simulations using GROMACS. Anxiolytic activity was assessed using the elevated plus maze (EPM) in animal models. Network pharmacology and ADMET profiling were conducted using publicly available databases and tools.</p><p><strong>Results: </strong>Docking studies revealed that all compounds exhibited higher binding affinity than diazepam, with m_02 showing the strongest interaction (-10.44 kcal/mol vs. -7.38 kcal/mol for diazepam). Molecular dynamics confirmed the stability of m_02 and m_03 at the receptor binding site. In EPM testing, m_03 demonstrated the most pronounced increase in time spent and entries into open arms, suggesting potential anxiolytic effects. Network pharmacology identified 72 overlapping targets, with KEGG pathway enrichment highlighting neuroactive ligand-receptor interaction and dopaminergic synapse pathways. ADMET analysis indicated favorable drug-like properties.</p><p><strong>Discussion: </strong>The chalcone-arylpiperazine hybrids showed promising in silico binding and behavioral effects, particularly m_03. Molecular dynamics and MM-PBSA analyses supported the stability and interaction profiles of key compounds. Network pharmacology suggested plausible mechanisms of action, though these remain speculative without further experimental validation.</p><p><strong>Conclusion: </strong>Chalcone-arylpiperazine hybrids represent a potentially valuable scaffold for antianxiety drug development. However, the mechanistic insights derived from computational studies require robust in vivo and mechanistic validation to confirm therapeutic relevance.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}