Central nervous system agents in medicinal chemistry最新文献

{"title":"Evaluation of Anti-epileptic Activity of Cyanthillium cinereum (L.) H. Rob. Leaves in the Experimental Pentylenetetrazole-induced Epileptic Model.","authors":"Kundan Singh Bora, Kanupriya Kumari","doi":"10.2174/0118715249352799250512015642","DOIUrl":"https://doi.org/10.2174/0118715249352799250512015642","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a common and frequently devastating disorder affecting millions of people. According to a recent survey, 1-2% of the Indian population suffers from major mental disorders and 5% suffers from minor mental disorders. Epilepsy is among those mental disorders that affect 30 million people worldwide. Currently, the treatment of epilepsy involves agents which modulate sodium-ion channels, enhance GABAergic transmission, and agents with multiple modes of action. Various classes of synthetic drugs are used to treat epilepsy, but these drugs are often challenged due to their unwanted side effects. Medicinal plants have been a part of human society which combating diseases from the dawn of civilization. The plant Cyanthillium cinereum (L.) H. Rob. is mainly found in the Himalayas from Kashmir to Nepal at an altitude of 8000 m. Decoction of this plant is traditionally used as an anti-cancer, anti-malarial, anti-epileptic, and in neurosis and skin diseases.</p><p><strong>Objectives: </strong>The present study investigated the anti-epileptic activity of Cyanthillium cinereum leaves against pentylenetetrazole (PTZ)-induced epileptic model in mice.</p><p><strong>Methods: </strong>Plant extracts were prepared using solvents in increasing polarity viz., petroleum ether, chloroform, ethanol, and water, using a Soxhlet apparatus. The bio-active extract was characterized using FTIR and GC techniques. In vivo antioxidants like GSH and SOD level, oxidative stress markers- MDA and hemoglobin and platelet count were also estimated in the animal brain.</p><p><strong>Results: </strong>Amongst all extracts tested, only ethanol extract of Cyanthillium cinereum significantly (p<0.05) inhibited generalized tonic-clonic seizures in PTZ-induced epilepsy in mice in a dose (100 or 200 mg/kg., p.o.) dependent manner. The dose of 200 mg/kg of extract exhibited the most significant effect. It is also found that treatment with ethanol extract on PTZ-induced epilepsy in mice significantly (p<0.05) reduces the duration of convulsion and delays the onset of clonic convulsion.</p><p><strong>Conclusion: </strong>The present findings suggest that the high amounts of phenols and flavonoids in the ethanol extract could be responsible for the anti-epileptic effect. Moreover, the ethanol extract also restored GSH, SOD and hemoglobin and platelet level and decreased oxidative marker- MDA content in the mice brain.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188704","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":"The Role of Novel Biomarkers in the Early Management of Peripheral Diabetic Neuropathy.","authors":"Jyoshna Rani Dash, Gurudutta Pattnaik, Gangadhar Pradhan, Choudhury Pratyush Kumar Baral, Biswajit Behera, Goutam Ghosh, Goutam Rath, Biswakanth Kar","doi":"10.2174/0118715249358465250522173332","DOIUrl":"https://doi.org/10.2174/0118715249358465250522173332","url":null,"abstract":"<p><p>Diabetes can frequently result in peripheral diabetic neuropathy (PDN), a lifethreatening illness that impairs the motor and sensory abilities of peripheral nerves. Prompt identification and management of peripheral neuropathy are essential to avert permanent nerve impairment and enhance the well-being of affected individuals. In addition, axonal degeneration is usually detected at a late stage of the disease and serves as a basis for developing modern diagnostic techniques. Novel biomarkers that can detect PDN early and track its development are thus required. In this review, we highlight the most recent developments in identifying and verifying putative biomarkers for PDN, emphasizing their connections to the pathophysiology and clinical presentations of the illness. The challenges and opportunities for developing biomarker-based diagnostic and therapeutic strategies for PDN are also discussed. It is suggested that biomarkers help predict the response and outcome of PDN treatments, such as poly (ADP-ribose) polymerase inhibitors and regenerative medicine.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188705","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":"Cerebroprotective Potential of Androgen Receptors in Ischemic Postconditioning against Cerebral Ischemia/Reperfusion-Induced Neurodegenerative Changes.","authors":"Prabhat Singh, Surbhi Gupta, Bhupesh Sharma, Lubhan Singh, Rani Bansal, Mamta Gupta","doi":"10.2174/0118715249354207250429041513","DOIUrl":"https://doi.org/10.2174/0118715249354207250429041513","url":null,"abstract":"<p><strong>Background and objective: </strong>In stroke, reperfusion of blood to the cerebral ischemic area following sustained ischemia further exacerbates tissue damage, identified as cerebral ischemia and reperfusion (I/R) insult. Ischemic post-conditioning (IPoC) appears to offer benefits against I/R injury. The cascade of androgen receptors (ARs) has a vital role in cerebral stroke; however, its neurodefensive function in IPoC is unclear. This investigation aimed to explore the involvement of ARs in IPoC in cerebral I/R insult in rats.</p><p><strong>Methods: </strong>Global cerebral ischemia/reperfusion (GCI/R) insult in experimental animals was provoked by 10 minutes of obstruction of the bilateral carotid arteries after reperfusion for 24 hours. IPoC was carried out by providing a triad of I/R insults with a gap of 10 minutes of GCI after 24 hours of reperfusion. Lateral push, inclined beam, rota rod, hanging wire, and Morris-water maze experimentations were conducted on animals to determine motor control and cognitive functions (learning and memory). Cerebral oxidative damage markers (raised lipid peroxidation and reduced glutathione levels), acetylcholinesterase (AChE) activity, inflammatory indicators (interleukin-6, interleukin-10, tumor necrosis factor-α, and myeloperoxidase), infarction, and histopathological alterations were also assessed.</p><p><strong>Results: </strong>Animals with I/R exhibited reduced motor function and memory along with raised cerebral oxidative damage, AChE activity, inflammation, infarction, and histopathological alterations. IPoC after ischemic events recuperated the damaging outcomes of I/R insult. 60 minutes before cerebral ischemia, pretreatment with testosterone mimicked the neurodefensive outcomes of IPoC. However, neuroprotective outcomes developed by IPoC were diminished by flutamide (ARs antagonist) pretreatment.</p><p><strong>Conclusion: </strong>IPoC may offer neuroprotective outcomes in I/R insult by modulation of ARmediated pathway.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082761","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":"Unveiling the Pharmacological Effects of Ginkgo biloba: Clinical Relevance and Applications.","authors":"Deepshi Arora, Yugam Taneja, Aakriti Saini, Bhawna Chopra, Manish Kumar, Shailendra Bhatt, Ajmer S Grewal, Ashwani K Dhingra","doi":"10.2174/0118715249362016250401085542","DOIUrl":"https://doi.org/10.2174/0118715249362016250401085542","url":null,"abstract":"<p><p>The consumption and utilization of Ginkgo biloba leaves and seeds in traditional herbal treatments have left an indelible mark. Their rich chemical makeup and remarkable pharmacological effects, particularly in the form of EGb761 leaf extracts, have captivated researchers seeking novel treatments for degenerative nerve illnesses like Alzheimer's disease. However, the story of Ginkgo biloba doesn't end there. The Ginkgo biloba seeds, which were once highly regarded as sustenance and medicine but are often overlooked, hold ancient wisdom that awaits discovery and understanding, also, it is advised to consume one to two seeds per day because of the ginkgo toxin side effect. Traditional Chinese medicine has harnessed its potential to combat intestinal tract worm infections, pyogenic skin diseases, enuresis, asthma, cough, and more, owing to its abundant reserves of carbs, protein, fat, and polyphenols. Moreover, recent studies have emerged, suggesting their neuroprotective properties. Fostering awareness and encouraging the consumption of Ginkgo biloba seeds thus becomes paramount. As we embark on a quest to delve into the depths of Ginkgo biloba seeds, this comprehensive review aims to shed light on their key components, bioactivities, processing techniques, and the latest insights into their pharmacological actions. By embracing a holistic understanding of Ginkgo biloba seeds, we lay the foundation for their scientific advancement and the development of this remarkable edible seed. Furthermore, it is essential to acknowledge that while Ginkgo biloba holds immense potential, caution is warranted, as adverse effects such as allergies have been reported, particularly in individuals with known allergies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031047","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":"An Updated Review of Potential Drug Targets for Japanese Encephalitis.","authors":"Roshni Singh, Sayak Sanyal, Nikita Basant, Somali Sanyal","doi":"10.2174/0118715249353956250326164211","DOIUrl":"https://doi.org/10.2174/0118715249353956250326164211","url":null,"abstract":"<p><p>Japanese encephalitis virus (JEV), first identified in 1935, continues to be a major threat to human health, especially in the Asia-Pacific region, where it remains prevalent. JEV, a neurotropic flavivirus, spreads through Culex tritaeniorhynchus mosquito bites and causes severe brain infections with high morbidity and mortality rates. Despite the availability of vaccines, no licensed anti-JEV drugs exist. This review provides a comprehensive overview of the epidemiology, structural and nonstructural proteins, and pathogenesis of JEV and explores potential drug targets. This study highlights both conventional and nonconventional drug targets, with a focus on nonstructural JEV proteins, which may hold promise for therapeutic development. This review also discusses drug targets shared by JEV and other flaviviruses, such as dengue, Zika, and West Nile virus, which reveal common pathways for viral entry and replication, along with distinct mechanisms specific to JEV. Key receptor interactions, including DC-SIGN, TAM receptor, sialic acid, LDLR, and CLEC5A interactions, are involved in JEV transmission and immune evasion. Additionally, the NMDA receptor has been identified as a critical player in JEV pathogenesis, suggesting new opportunities for neuroprotective therapies. A major obstacle in JEV drug development is the blood-brain barrier (BBB), which hinders the delivery of therapeutic agents to the central nervous system (CNS). Recent research has emphasized the need for innovative drug delivery systems that can cross the BBB, reducing viral replication and neural damage. While clinical trials with traditional antivirals have yielded mixed results, live attenuated and inactivated vaccines have shown promise in preventing JEV infection. Additionally, nucleic acid-based therapies, including microRNAs and short hairpin RNAs (shRNAs), are emerging as potential treatments, with nanoparticle-based delivery systems offering solutions to overcome BBB challenges. This review underscores the need for an integrated approach, including improved vaccines, targeted drug delivery strategies, and novel therapeutics, to effectively combat JEV infections on a global scale.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026608","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":"Exploring the Potential of Dolutegravir in Alzheimer's Disease Treatment: Insights from Network Pharmacology and In Silico Docking Studies.","authors":"Karishma M Rathi, Nikhil S Sakle, Vaishali R Undale, Ravindra D Wavhale, Ritesh P Bhole, Pawan N Karwa","doi":"10.2174/0118715249350698250317041551","DOIUrl":"https://doi.org/10.2174/0118715249350698250317041551","url":null,"abstract":"<p><strong>Background: </strong>The search for effective treatments for neurodegenerative diseases, particularly Alzheimer's disease, has been fraught with challenges. Alzheimer's disease accounts for 60-80% of dementia cases globally, affecting approximately about 50 million people. Currently, drug repurposing has emerged as a promising strategy in new drug development, attracting significant attention from regulatory agencies, such as the US FDA.</p><p><strong>Aim: </strong>This study aimed to investigate the potential therapeutic role of dolutegravir in Alzheimer's disease (AD) treatment using a novel network pharmacology approach. Specifically, it explored the interaction of dolutegravir with key molecular targets involved in AD pathology, predicted its effects on relevant biological pathways, and evaluated its viability as a new therapeutic candidate.</p><p><strong>Objective: </strong>This study employed a network pharmacology framework to evaluate dolutegravir, an antiretroviral drug, as a potential treatment for Alzheimer's disease, shedding light on its possible therapeutic mechanisms.</p><p><strong>Method: </strong>A network pharmacology approach was used to predict the drug targets of dolutegravir. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify interacting pathways. Additionally, protein- protein interaction (PPI) network analysis was conducted to assess key interactions and molecular docking studies were performed to evaluate the binding affinity of dolutegravir to the predicted targets.</p><p><strong>Result: </strong>PPI network analysis revealed that dolutegravir interacted with several key targets, including BRAF, mTOR, MAPK1, MAPK3, NOS1, BACE1, CAPN1, CASP3, CASP7, CASP8, CHUK, IKBKB, PIK3CA, and PIK3CD. KEGG pathway analysis suggested that dolutegravir could influence amyloid-beta formation, amyloid precursor protein metabolism, and the cellular response to amyloid-beta. Molecular docking results showed the highest binding affinity of dolutegravir for PI3KCD (-8.5 kcal/mol) and MTOR (-8.7 kcal/mol).</p><p><strong>Conclusion: </strong>The findings indicated that dolutegravir holds significant potential in modulating key pathways involved in Alzheimer's disease pathogenesis. These results provide a strong foundation for further investigations into the therapeutic efficacy and safety of dolutegravir in the treatment of Alzheimer's disease. The use of drug repurposing strategies, leveraging Dolutegravir's established pharmacological profile, offers a promising route for accelerated therapeutic development in AD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014350","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":"Analysis of Vit B6 in Raw Banana Peel, Phytochemical Screening, and Neuroprotective Effects.","authors":"Priyabrata Pradhan, Vineet Kumar Rai, Saroj Kumar Rout, Biswakanth Kar, Durgamadhab Kar, Shakti Ketan Prusty, Goutam Ghosh, Goutam Rath","doi":"10.2174/0118715249373404250403072724","DOIUrl":"https://doi.org/10.2174/0118715249373404250403072724","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy contributes significantly to the burden of mental illness, with an estimated 50 million cases globally. Neuroprotection with herbal bioactives is a promising therapeutic strategy for the prevention and treatment of temporal lobe epilepsy. Banana peel is rich in antioxidants and anti-inflammatory compounds. It has the potency to protect against neuronal apoptosis primarily due to the presence of Vit B6 and flavones.</p><p><strong>Objectives: </strong>This: study investigated the neuroprotective effects of Hydro-Alcoholic Extracts (HAE) of banana peel, prepared at solvent ratios of 90:10, 80:20, and 70:30, focusing on their anti- apoptotic, antioxidant, and anti-inflammatory activities.</p><p><strong>Methods: </strong>Neurons or neuronal cell lines were treated with HAE at 10-200 μg/mL concentrations. Apoptotic markers (cleaved caspase-3 and Bcl-2) were evaluated using ELISA, and the cleaved caspase-3/Bcl-2 ratio was calculated. Antioxidant effects were assessed via Glutamate Decarboxylase (GAD) and catalase activity assays, while pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were quantified. Cell viability was analyzed using the MTT assay, and IC50 values were determined for apoptosis inhibition.</p><p><strong>Results: </strong>HAE (90:10) at 100 μg/mL significantly reduced the cleaved caspase-3/Bcl-2 ratio (0.45±0.02), with an IC50 of 37.5±2.1 μg/mL, demonstrating superior anti-apoptotic activity. HAE (80:20) and HAE (70:30) exhibited IC50 values of 48.2±2.5 μg/mL and 62.7±3.0 μg/mL, respectively, indicating comparatively lower potency. Enhanced GAD (121.4±5.2 U/mg) and catalase (89.7±3.4 U/mg) activities with HAE (90:10) highlight its potent antioxidant effects. Significant reductions in pro-inflammatory markers, including TNF-α (decreased by 45.6±2.3% at 100 μg/mL), further underscore its anti-inflammatory potential. The MTT assay revealed improved cell viability, with HAE (90:10) maintaining 93.5±2.6% viability at 100 μg/mL. The superior performance of HAE (90:10) can be attributed to its optimized balance of bioactive compounds, supporting its neuroprotective properties.</p><p><strong>Conclusion: </strong>HAE (90:10) emerged as the most promising candidate for neuroprotection, demonstrating potent anti-apoptotic, antioxidant, and anti-inflammatory effects. These findings suggest its potential application in managing neurodegenerative disorders, warranting further in vivo and clinical studies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060300","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":"Study of the Antidepressant Effects of the Combination of Agmatine and Melatonin Following Restraint Stress in Mice: the Role of Oxidative Factors.","authors":"Saeed Mehrzadi, Ali Jamshidi Naeini, Fahime Azimirad, Azam Hosseinzadeh","doi":"10.2174/0118715249347833250307041355","DOIUrl":"https://doi.org/10.2174/0118715249347833250307041355","url":null,"abstract":"<p><strong>Objective: </strong>Major Depressive Disorder (MDD) is a psychiatric disorder that has a tight connection to stressful experiences, decreased levels of endogenous antioxidants and enhanced levels of oxidative stress. We drafted this research to define the results of combining agmatine and melatonin on stress-induced depression in mice.</p><p><strong>Methods: </strong>Experimental groups included the non-stressed group treated with vehicle (ethanol at a concentration of 0.0005%), stressed vehicle (ethanol at a concentration of 0.0005%)-treated group, group treated with fluoxetine (10 mg/kg/day), group treated with melatonin (10 mg/kg/day), group treated with agmatine (1 mg/kg/day), group receiving a combination of melatonin (10 mg/kg/day) and agmatine (1 mg/kg/day). The animals were subjected to restraint stress for two hours daily for a duration of one week, concurrently with the daily oral administration of agents through drinking water. Open field test and forced swimming test were operated on the 8th day. The oxidative stress markers were measured in the mice hippocampus.</p><p><strong>Results: </strong>Stress led to the elevation of immobility time. The combination group showed a significant effect in comparison to the agmatine and melatonin groups. The combination of melatonin and agmatine was successful in the elevation of hippocampus catalase activity; and this effect was comparable in the fluoxetine group. We observed enhancement of superoxide dismutase activity in treatment groups and reduction in malondialdehyde levels in melatonin, agmatine and combination groups.</p><p><strong>Conclusion: </strong>A combination of agmatine and melatonin improves stress-induced depression more effectively than each alone, which may result from suppressing oxidative stress.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722746","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":"Identification of Pharmacophore Responsible for the JNK3 Enzyme Inhibition using KPLS-based QSAR Analysis.","authors":"Ravi Kumar Rajan, Maida Engels, Umaa Kuppuswamy","doi":"10.2174/0118715249345667250216034023","DOIUrl":"https://doi.org/10.2174/0118715249345667250216034023","url":null,"abstract":"<p><strong>Background: </strong>The pharmacophoric approach relies on the theory of possessing ubiquitous chemical functionalities, and carrying a uniform spatial conformation that provides a route to enhanced potency on the same target receptor. JNK3, also known as c-Jun N-terminal kinase 3, is a protein kinase that plays a crucial role in various cellular processes, particularly in the central nervous system (CNS). In this study, a kernel-based partial least square (KPLS)- based Two-dimensional Quantitative structural activity relationship (2D QSAR) model to predict pharmacophores responsible for c-Jun-N-terminal kinase 3 (JNK3) inhibition.</p><p><strong>Method: </strong>A library of small molecule JNK3 inhibitors was created from the literature, and a predictive model was built using Canvas 2.6.</p><p><strong>Result: </strong>The analysis revealed key structural determinants of activity. Compounds with high pIC50 values (>6) showed numerous favorable contributions, particularly secondary benzamide nitrogen and methylene groups. Steric effects were more influential than inductive effects, with bulkier groups like t-butyl reducing activity. Positive contributions were observed with OH, OCH3, and -F substituents, while unfavorable effects were linked to tertiary nitrogen, methyl, and primary amino groups. Substituted sulphonamides and benzotriazole moieties enhanced activity unless modified with amino or carbonyl groups. Favorable contributions were noted for terminal heterocyclic rings like pyrimidinyl acetonitrile, whereas phenyl substitutions and certain piperazine configurations were detrimental. Hydrogen in the urea moiety and avoiding bulky substitutions were crucial for activity. These insights guide the design of potent JNK3 inhibitors.</p><p><strong>Conclusion: </strong>The present study highlights the significant impact of substituents on molecular activity, with steric effects, particularly on the phenyl ring, playing a dominant role. Favorable contributions are linked to substitutions like hydroxyl, methoxy, and fluorine, while bulky and meta substitutions reduce activity. Functional groups like unsubstituted sulfonamide or free hydrogen in urea are crucial for activity. Insights into steric, electronic, and positional factors, combined with analysis of JNK3 inhibitors, will guide the design of more selective molecules.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544915","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":"Integrative Analysis of the Impact of Prenatal Depression on the Newborn Intestinal Microbiota.","authors":"Wafaa Taha, Oumaima Anachad, Amine Taouil, Chaimaa Saadoune, Mariame El Messal, Faiza Bennis, Fatima Chegdani","doi":"10.2174/0118715249361952250209084153","DOIUrl":"https://doi.org/10.2174/0118715249361952250209084153","url":null,"abstract":"<p><strong>Background: </strong>More than 15% of women develop symptoms of depression during pregnancy, which often affects the mental and physical development of the newborn by altering its intestinal microbiota. Previous studies revealed that the gut microbiota plays a crucial role in the maturation of systems involved in the gut-brain axis, including the gastrointestinal system, the immune system, and the hypothalamic-pituitary-adrenal system axis.</p><p><strong>Methods: </strong>This study aims to explore the cross-talk between the prenatal depression process and neonatal intestinal microbiota diversity. A total of 100 differentially expressed genes (DEGs) associated with prenatal depression were collected from various scientific publications and databases. Bioinformatics tools were used to analyze these DEGs. The STRING database. ToppGene database and DICE were employed for this integrative analysis.</p><p><strong>Results: </strong>The network generated by the STRING database identified six pivotal genes: TNF, BDNF, IL-6, NR3C1, IGF2, and POMC. These genes regulate response to endogenous hormones, particularly cortisol secretion in newborns, as well as inhibiting serotonin secretion. Moreover, these genes are linked to major depressive disorder and other mental diseases, contributing to maternal and neonatal gut microbiota dysbiosis. Analysis using ToppGene and DICE's further validated the biological processes identified by String, including the regulation of cellular cortisol secretion, metabolic processes, and serotonin inhibition.</p><p><strong>Conclusion: </strong>The bioinformatics tools employed in this study allowed us to identify pivotal genes involved in prenatal depression, their associated signaling pathways, and their roles in modulating maternal and neonatal gut microbiota.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517688","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}