Central nervous system agents in medicinal chemistry最新文献

筛选
英文 中文
Filtration of Natural Derivatives as MAO Inhibitors by Virtual Screening: A Potential Lead for Neurodegenerative Disorders. 通过虚拟筛选过滤天然衍生物作为 MAO 抑制剂:治疗神经退行性疾病的潜在药物。
Central nervous system agents in medicinal chemistry Pub Date : 2024-04-04 DOI: 10.2174/0118715249284642240326045923
Neelam Malik, Supriya Agnihotri, Priyanka Dhiman
{"title":"Filtration of Natural Derivatives as MAO Inhibitors by Virtual Screening: A Potential Lead for Neurodegenerative Disorders.","authors":"Neelam Malik, Supriya Agnihotri, Priyanka Dhiman","doi":"10.2174/0118715249284642240326045923","DOIUrl":"https://doi.org/10.2174/0118715249284642240326045923","url":null,"abstract":"AIM\u0000The purpose of the current study was to explore the virtual library for the screening against Monoamine oxidase (MAO) isoforms. An in-house library of natural based ligands was docked within the active sites of MAO isoforms and their in vitro study was also conducted.\u0000\u0000\u0000OBJECTIVE\u0000The prime objective of the current study was to screen and validate the natural-based derivatives for MAO inhibitory action with the least adverse effects and get molecular aspects about further structural modifications on the most active leads.\u0000\u0000\u0000BACKGROUND\u0000The importance of MAOs in controlling the activity of the central nervous system has been extensively studied. Our goal in this work is to identify a prospective natural lead molecule that has a stronger affinity for the MAO enzyme in order to produce a more effective natural candidate for a neurological agent.\u0000\u0000\u0000RESULTS\u0000In order to get insight into how different categories of natural compounds interact with the targeted protein, we virtually screened the numerous natural compound categories in the current study. Rhamnetin, quercetin, piperine, eugenol, and umbelliferone showed the highest dock scores in the case of MAO-B, with scores of -10.57, -9.938, -9.445, and 7.821, respectively. For MAO-A, umbelliferone, curcumin, caffeic acid, and quercetin, the corresponding dock scores were -8.001, -7.941, -7.357, and -6.658. Additionally, an in vitro MAO inhibitory experiment was utilized to assess the top-ranked compounds with the best docking scores. The most potent Human Monoamine oxidase (hMAO-A) inhibitor, with an IC50 of 10.98±0.006 M and a selectivity index (SI) of 0.607, was discovered to be the compound umbelliferone. Rhamnetin, the lead chemical, has demonstrated hMAO-B activity with a value of 10.32±0.044 M (SI value of 3.096).\u0000\u0000\u0000CONCLUSION\u0000These natural potential ligands have been found remarkable to the standard compounds against MAO-A and MAO-B, and they could be used as a lead chemical in the development of novel therapeutic candidates. The in silico screening results and in vitro hMAO inhibitory efficacy exhibited strong correlations.","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140741485","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}
引用次数: 0
Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting. 纳米医学:阿尔茨海默病药物靶向治疗的新前沿。
Central nervous system agents in medicinal chemistry Pub Date : 2024-03-28 DOI: 10.2174/0118715249281331240325042642
Kalyani Pathak, Mohammad Zaki Ahmad, Riya Saikia, Manash Pratim Pathak, Jon Jyoti Sahariah, Parimita Kalita, Aparoop Das, Md Ariful Islam, Pallab Pramanik, Dubom Tayeng, Basel A Abdel-Wahab
{"title":"Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting.","authors":"Kalyani Pathak, Mohammad Zaki Ahmad, Riya Saikia, Manash Pratim Pathak, Jon Jyoti Sahariah, Parimita Kalita, Aparoop Das, Md Ariful Islam, Pallab Pramanik, Dubom Tayeng, Basel A Abdel-Wahab","doi":"10.2174/0118715249281331240325042642","DOIUrl":"https://doi.org/10.2174/0118715249281331240325042642","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein-mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320127","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}
引用次数: 0
WITHDRAWN: Exploring The Diverse Therapeutic Potentials of Synthetic Analogues of Keto-terpenoids (+) Carvone: A Future Scaffold 探索酮三萜类合成类似物 (+) 香芹酮的多种治疗潜力:未来的支架。
Central nervous system agents in medicinal chemistry Pub Date : 2024-03-27 DOI: 10.2174/0118715249278766240322054108
Snigdha Srivastava, Reema Sinha, Rahul Kaushik, Rajan Kumar Kurmi
{"title":"WITHDRAWN: Exploring The Diverse Therapeutic Potentials of Synthetic Analogues of Keto-terpenoids (+) Carvone: A Future Scaffold","authors":"Snigdha Srivastava, Reema Sinha, Rahul Kaushik, Rajan Kumar Kurmi","doi":"10.2174/0118715249278766240322054108","DOIUrl":"10.2174/0118715249278766240322054108","url":null,"abstract":"<p><p>The article has been withdrawn at the request of the authors of the journal \"Central Nervous System Agents in Medicinal Chemistry\" as a conflict has arisen among the authors in adding another author at the later stage of publication</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320126","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}
引用次数: 0
Effect of Flavonoids against Parkinson's Disease. 类黄酮对帕金森病的疗效
Central nervous system agents in medicinal chemistry Pub Date : 2024-01-01 DOI: 10.2174/0118715249264078231214074107
Himanshi Varshney, Yasir Hasan Siddique
{"title":"Effect of Flavonoids against Parkinson's Disease.","authors":"Himanshi Varshney, Yasir Hasan Siddique","doi":"10.2174/0118715249264078231214074107","DOIUrl":"10.2174/0118715249264078231214074107","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterized by the depletion of striatal dopamine content and aggregation of alphasynuclein in the substantia nigra (SN). It is possible to treat the symptoms of PD with a variety of medications, but they often result in complications and are not able to cure or stop the progression of the disease. Flavonoids (the phytocomponents present in almost all fruits and vegetables) are the class of secondary metabolites that have generated a peak of interest because of their medicinal properties, including a reduction in the risk of PD. Several flavonoids such as quercetin, kaempferol, hesperitin, anthocyanin and many more have been reported for their anti- Parkinson's effect. This review deals with the neuroprotective benefits of different classes of flavonoids against PD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673886","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}
引用次数: 0
Marine-derived Compounds: A Powerful Platform for the Treatment of Alzheimer's Disease. 海洋衍生化合物:治疗阿尔茨海默病的强大平台。
Central nervous system agents in medicinal chemistry Pub Date : 2024-01-01 DOI: 10.2174/0118715249269050231129103002
Rashmi Arora, Ritchu Babbar, Abhishek Dabra, Bhawna Chopra, Geeta Deswal, Ajmer Singh Grewal
{"title":"Marine-derived Compounds: A Powerful Platform for the Treatment of Alzheimer's Disease.","authors":"Rashmi Arora, Ritchu Babbar, Abhishek Dabra, Bhawna Chopra, Geeta Deswal, Ajmer Singh Grewal","doi":"10.2174/0118715249269050231129103002","DOIUrl":"10.2174/0118715249269050231129103002","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a debilitating form of dementia that primarily affects cholinergic neurons in the brain, significantly reducing an individual's capacity for learning and creative skills and ultimately resulting in an inability to carry out even basic daily tasks. As the elderly population is exponentially increasing, the disease has become a significant concern for society. Therefore, neuroprotective substances have garnered considerable interest in addressing this universal issue. Studies have shown that oxidative damage to neurons contributes to the pathophysiological processes underlying AD progression. In AD, tau phosphorylation and glutamate excitotoxicity may play essential roles, but no permanent cure for AD is available. The existing therapies only manage the early symptoms of AD and often come with numerous side effects and toxicities. To address these challenges, researchers have turned to nature and explored various sources such as plants, animals, and marine organisms. Many historic holy books from different cultures emphasize that adding marine compounds to the regular diet enhances brain function and mitigates its decline. Consequently, researchers have devoted significant time to identifying potentially active neuroprotective substances from marine sources. Marine-derived compounds are gaining recognition due to their abundant supply of diverse chemical compounds with biological and pharmacological potential and unique mechanisms of action. Several studies have reported that plants exhibit multitarget potential in treating AD. In light of this, the current study focuses on marine-derived components with excellent potential for treating this neurodegenerative disease.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673887","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}
引用次数: 0
Effectiveness of Novel Drug Delivery System using Curcumin in Alzheimer's Disease. 使用姜黄素的新型给药系统对阿尔茨海默病的疗效
Central nervous system agents in medicinal chemistry Pub Date : 2024-01-01 DOI: 10.2174/0118715249279534240214111155
Urmila Aswar, Kundlik Rathod, Dyandevi Mathure
{"title":"Effectiveness of Novel Drug Delivery System using Curcumin in Alzheimer's Disease.","authors":"Urmila Aswar, Kundlik Rathod, Dyandevi Mathure","doi":"10.2174/0118715249279534240214111155","DOIUrl":"10.2174/0118715249279534240214111155","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a form of brain degeneration that gradually impairs a person's memory and cognitive skills, eventually making it harder for them to perform everyday activities. Its pathophysiology has been attributed to the deposition of amyloid β (Aβ), neurofibrillary tangles (NFT), and α-synuclein (A-s) in some cases. Presently, 4 drugs have been approved for the treatment. They are Donepezil, Rivastigmine, Galantamine and Memantine. The first three are acetylcholinesterase inhibitors, while memantine is an NMDA receptor antagonist. Even though these medications are successful in treating mild to moderate Alzheimer's disease, they have not been able to reverse the disease or even slow its progression completely. Hence, natural products are gaining more popularity due to the advantage of the multitarget intervention effect. The most investigated spice, <i>Curcuma longa</i>'s bioactive component, curcumin, has demonstrated anti-amyloid, anti-NFT, and anti-Lewy body properties and substantial antiinflammatory, antioxidant, and antiapoptotic properties. However, its proven neuroprotective activity is hampered by many factors, such as poor water solubility and bioavailability. Therefore, many novel formulations have been designed to improve its bioavailability with methods such as 1) Micellar Solubilization, 2) Cyclodextrin Complexation, 3) Crystal Modification, and 4) Particle Size Reduction, etc. The current chapter aims to summarize various novel formulations of curcumin and their effectiveness in treating AD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975017","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}
引用次数: 0
Neuroprotective Effects of Isolated Mangiferin from Swertia chirayita Leaves Regulating Oxidative Pathway on Streptozotocin-Induced Diabetic Neuropathy in Experimental Rats. 从獐牙菜叶中分离的芒果苷调节氧化途径对链脲佐菌素诱导的实验大鼠糖尿病神经病变的神经保护作用
Central nervous system agents in medicinal chemistry Pub Date : 2024-01-01 DOI: 10.2174/0118715249255977231213053039
Shivam, Asheesh Kumar Gupta
{"title":"Neuroprotective Effects of Isolated Mangiferin from <i>Swertia chirayita</i> Leaves Regulating Oxidative Pathway on Streptozotocin-Induced Diabetic Neuropathy in Experimental Rats.","authors":"Shivam, Asheesh Kumar Gupta","doi":"10.2174/0118715249255977231213053039","DOIUrl":"10.2174/0118715249255977231213053039","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress has an important role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complication of diabetes mellitus. <i>Swertia chirayita</i> is a rich source of phenolic constituents and has hypoglycemic, anti-inflammatory, and antioxidant properties.</p><p><strong>Aims: </strong>This study was performed to evaluate the neuroprotective effect in diabetes by enhancing antioxidant defense against oxidative stress, which exhibits a neuroprotective effect in streptozotocin- induced diabetic rats.</p><p><strong>Objectives: </strong>The objective of this study was to elucidate the therapeutic potential of bioactive compounds of <i>Swertia chirayita</i> for diabetic complications.</p><p><strong>Methods: </strong>The present work focused on isolating the bioactive from the leaves of Swertia absinthe for acute toxicity studies, assessing its protective effects against diabetes and diabetic neuropathy as well as its mode of action in STZ-induced Wistar rats. The local area of Moradabad is the place from where the leaves of <i>Swertia chirayita</i> were gathered. Mangiferin was isolated and identified using spectroscopic techniques, such as UV, HPLC, 1H NMR, C13 NMR, MAS, and FTIR. Mangiferin was administered in doses of 15 and 30 mg/kg to test its effect on experimentally induced diabetes. The sciatic nerves of all groups were examined histopathologically. The protective effect of the drug against diabetes and diabetic neuropathy was demonstrated by measures, such as blood glucose level, body weight, food intake, thermal hyperalgesia, grip strength, spontaneous locomotor test, and lipid profile analysis. Sciatic nerve cells of the treated groups showed less inflammation, degeneration, and necrosis.</p><p><strong>Results: </strong>The results of this study confirmed that mangiferin alleviated diabetic neuropathic pain, possibly by reducing inflammatory cytokines (TNF-α, TGF-β1, IL-1β, and IL-6), strong antioxidant activity, and NGF in sciatic nerves. It may be a therapeutic agent.</p><p><strong>Conclusion: </strong>Our results suggested that active phytochemicals of <i>Swertia chirayita</i> showed preventive and curative effects against STZ-induced diabetic neuropathy in rats, which might be due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673889","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}
引用次数: 0
Assessing Blood-brain Barrier Function in the Context of Pain Management. 评估疼痛治疗中的血脑屏障功能
Central nervous system agents in medicinal chemistry Pub Date : 2024-01-01 DOI: 10.2174/0118715249283159240316091312
Farshad Hassanzadeh Kiabi, Saeed Gharooee Ahangar, Siavash Beiranvand
{"title":"Assessing Blood-brain Barrier Function in the Context of Pain Management.","authors":"Farshad Hassanzadeh Kiabi, Saeed Gharooee Ahangar, Siavash Beiranvand","doi":"10.2174/0118715249283159240316091312","DOIUrl":"10.2174/0118715249283159240316091312","url":null,"abstract":"<p><p>One essential component of the neurovascular system is known as the blood-brain barrier (BBB). This highly effective biological barrier plays a pivotal role in regulating the brain's internal microenvironment and carefully controlling the passage of various chemicals into and out of the brain. Notably, it serves as a safeguard for the brain, particularly when it comes to the selective transportation of drugs like opioids and non-steroidal anti-inflammatory medications (NSAIDs), which are commonly used in the management of chronic pain. It's important to note that during the development of chronic pain, the activation of microglia and astrocytes can potentially disrupt or damage the integrity of the BBB. In this comprehensive review, we aim to delve into the intricate interplay between the blood-brain barrier and the transportation of pain-relieving drugs, shedding light on the challenges and mechanisms involved in this process.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178237","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}
引用次数: 0
Lead Identification Through In Silico Studies: Targeting Acetylcholinesterase Enzyme Against Alzheimer's Disease. 通过硅学研究确定先导物:以乙酰胆碱酯酶为靶点防治阿尔茨海默病。
Central nervous system agents in medicinal chemistry Pub Date : 2024-01-01 DOI: 10.2174/0118715249268585240107184956
Dhairiya Agarwal, Sumit Kumar, Ramesh Ambatwar, Neeru Bhanwala, Lokesh Chandrakar, Gopal L Khatik
{"title":"Lead Identification Through <i>In Silico</i> Studies: Targeting Acetylcholinesterase Enzyme Against Alzheimer's Disease.","authors":"Dhairiya Agarwal, Sumit Kumar, Ramesh Ambatwar, Neeru Bhanwala, Lokesh Chandrakar, Gopal L Khatik","doi":"10.2174/0118715249268585240107184956","DOIUrl":"10.2174/0118715249268585240107184956","url":null,"abstract":"<p><strong>Aims: </strong>In this work, we aimed to acquire the best potential small molecule for Alzheimer's disease (AD) treatment using different models in Biovia Discovery Studio to identify new potential inhibitors of acetylcholinesterase (AChE) <i>via in silico</i> studies.</p><p><strong>Background: </strong>The prevalence of cognitive impairment-related neurodegenerative disorders, such as AD, has been observed to escalate rapidly. However, we still know little about the underlying functions, outcome predictors, or intervention targets causing AD.</p><p><strong>Objectives: </strong>The objective of the study was to optimize and identify the lead compound to target AChE against Alzheimer's disease.</p><p><strong>Methods: </strong>Different <i>in silico</i> studies were employed, including the pharmacophore model, virtual screening, molecular docking, <i>de novo</i> evolution model, and molecular dynamics.</p><p><strong>Results: </strong>The pharmacophoric features of AChE inhibitors were determined by ligand-based pharmacophore models and 3D QSAR pharmacophore generation. Further validation of the best pharmacophore model was done using the cost analysis method, Fischer's randomization method, and test set. The molecules that harmonized the best pharmacophore model with the estimated activity < 1 nM and ADMET parameters were filtered, and 12 molecules were subjected to molecular docking studies to obtain binding energy. 3vsp_EK8_1 secured the highest binding energy of 65.60 kcal/mol. Further optimization led to a 3v_Evo_4 molecule with a better binding energy of 70.17 kcal/mol. The molecule 3v_evo_4 was subjected to 100 ns molecular simulation compared to donepezil, which showed better stability at the binding site.</p><p><strong>Conclusion: </strong>A lead compound, 3v_Evo_4 molecule, was identified to inhibit AChE, and it could be further studied to develop as a drug with better efficacy than the existing available drugs for treating AD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577140","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}
引用次数: 0
Glutamate Receptors and C-ABL Inhibitors: A New Therapeutic Approach for Parkinson's Disease. 谷氨酸受体和 C-ABL 抑制剂:帕金森病的新治疗方法。
Central nervous system agents in medicinal chemistry Pub Date : 2024-01-01 DOI: 10.2174/0118715249268627231206115942
Priya P Shejul, Gaurav M Doshi
{"title":"Glutamate Receptors and C-ABL Inhibitors: A New Therapeutic Approach for Parkinson's Disease.","authors":"Priya P Shejul, Gaurav M Doshi","doi":"10.2174/0118715249268627231206115942","DOIUrl":"10.2174/0118715249268627231206115942","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second-most prevalent central nervous system (CNS) neurodegenerative condition. Over the past few decades, suppression of BCR-Abelson tyrosine kinase (c-Abl), which serves as a marker of -synuclein aggregation and oxidative stress, has shown promise as a potential therapy target in PD. c-Abl inhibition has the potential to provide neuroprotection against PD, as shown by experimental results and the first-in-human trial, which supports the strategy in bigger clinical trials. Furthermore, glutamate receptors have also been proposed as potential therapeutic targets for the treatment of PD since they facilitate and regulate synaptic neurotransmission throughout the basal ganglia motor system. It has been noticed that pharmacological manipulation of the receptors can change normal as well as abnormal neurotransmission in the Parkinsonian brain. The review study contributes to a comprehensive understanding of the approach toward the role of c-Abl and glutamate receptors in Parkinson's disease by highlighting the significance and urgent necessity to investigate new pharmacotherapeutic targets. The article covers an extensive insight into the concept of targeting, pathophysiology, and c-Abl interaction with α-synuclein, parkin, and cyclin-dependent kinase 5 (Cdk5). Furthermore, the concepts of Nmethyl- D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA) receptor, and glutamate receptors are discussed briefly. Conclusion: This review article focuses on in-depth literature findings supported by an evidence-based discussion on pre-clinical trials and clinical trials related to c-Abl and glutamate receptors that act as potential therapeutic targets for PD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565323","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信