Pub Date : 2024-04-30DOI: 10.2174/0115680266289292240420062705
Gulzar Muhammad, Muhammad Ajaz Hussain, Zahid Shafiq, Adnan Ashraf, Umer Shafique, Ajmal Khan, Asaad Khalid, Javid Hussain, Ahmed Al-Harrasi
: Berbamine (Ber) is an active medicinal bisbenzylisoquinoline alkaloid, which is usually obtained from different plants of the genus Berberis (family Berberidaceae) and is used to cure various disorders in traditional Chinese and Ayurvedic systems of medicine. Numerous in-vitro and in-vivo studies revealed the apoptotic and cytotoxic potential of Ber against different cell lines (SMMC-7721, A549, MDA-MB-231, and K562) by upregulating pro-apoptotic (Bax, p53) and downregulating anti-apoptotic (Bcl-2, survivin) proteins. Other pharmacological attributes ascribed to Ber included cardioprotective, anti-diabetic, anti-inflammatory, antimalarial, antioxidant, anti-hypercholesterolemic, and anti-allergic. Moreover, the synergistic effect of Ber improved the therapeutic potential of different drugs (paclitaxel (PTL), gemcitabine, dexamethasone, doxorubicin (DOX), and celecoxib) in different models. Various attempts could fabricate biologically active derivatives of Ber, such as 4-chlorobenzoyl berbamine (CBB) and O-4- ethoxyl-butyl-berbamine (EBB). The review focuses on the medicinal applications of Ber, particularly anti-cancer, cardioprotective, and anti-inflammatory, along with the mechanism of action.
:小檗胺（Berbamine，Ber）是一种活性药用双苄基异喹啉生物碱，通常从小檗科小檗属的不同植物中提取，在传统中医和阿育吠陀医学体系中用于治疗各种疾病。大量体外和体内研究表明，小檗通过上调促凋亡蛋白（Bax、p53）和下调抗凋亡蛋白（Bcl-2、survivin），对不同细胞株（SMMC-7721、A549、MDA-MB-231 和 K562）具有凋亡和细胞毒性潜力。Ber 的其他药理作用还包括保护心脏、抗糖尿病、抗炎、抗疟、抗氧化、抗高胆固醇血症和抗过敏。此外，在不同的模型中，Ber 的协同作用提高了不同药物（紫杉醇（PTL）、吉西他滨、地塞米松、多柔比星（DOX）和塞来昔布）的治疗潜力。各种尝试可以制造出具有生物活性的伯胺衍生物，如 4-氯苯甲酰伯胺（CBB）和 O-4-乙氧基丁基伯胺（EBB）。这篇综述重点介绍了 Ber 的医学应用，尤其是抗癌、保护心脏和抗炎方面，以及其作用机制。
{"title":"Pharmacological and Therapeutic Potential of Berbamine: A Potent Alkaloid from Genus Berberis","authors":"Gulzar Muhammad, Muhammad Ajaz Hussain, Zahid Shafiq, Adnan Ashraf, Umer Shafique, Ajmal Khan, Asaad Khalid, Javid Hussain, Ahmed Al-Harrasi","doi":"10.2174/0115680266289292240420062705","DOIUrl":"https://doi.org/10.2174/0115680266289292240420062705","url":null,"abstract":": Berbamine (Ber) is an active medicinal bisbenzylisoquinoline alkaloid, which is usually obtained from different plants of the genus Berberis (family Berberidaceae) and is used to cure various disorders in traditional Chinese and Ayurvedic systems of medicine. Numerous in-vitro and in-vivo studies revealed the apoptotic and cytotoxic potential of Ber against different cell lines (SMMC-7721, A549, MDA-MB-231, and K562) by upregulating pro-apoptotic (Bax, p53) and downregulating anti-apoptotic (Bcl-2, survivin) proteins. Other pharmacological attributes ascribed to Ber included cardioprotective, anti-diabetic, anti-inflammatory, antimalarial, antioxidant, anti-hypercholesterolemic, and anti-allergic. Moreover, the synergistic effect of Ber improved the therapeutic potential of different drugs (paclitaxel (PTL), gemcitabine, dexamethasone, doxorubicin (DOX), and celecoxib) in different models. Various attempts could fabricate biologically active derivatives of Ber, such as 4-chlorobenzoyl berbamine (CBB) and O-4- ethoxyl-butyl-berbamine (EBB). The review focuses on the medicinal applications of Ber, particularly anti-cancer, cardioprotective, and anti-inflammatory, along with the mechanism of action.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Sphingosine 1-phosphate (S1P) is extensively researched as a lysophospholipid and is crucial in various physiological and pathological processes. It achieves this via signalling through five different subtypes of G protein-coupled receptors (GPCRs), namely S1PR1 to S1PR5. S1PR modulators possess the ability to traverse the blood-brain barrier, potentially leading to direct ac-tions within the Central Nervous System (CNS). S1PR modulators specifically bind to receptors located on the surface of naive and central memory lymphocytes, causing these cells to be trapped or confined within the lymph node. The investigation of the S1P pathway has resulted in the ap-proval of three S1PR modulators, namely fingolimod, siponimod, and ozanimod, as medications for the treatment of patients suffering from Multiple Sclerosis (MS). Additionally, new S1PR modulators, such as ponesimod and etrasimod, are currently being developed and tested in clini-cal trials. Research on the creation of S1P modulators in neurodegenerative illnesses is ongoing as scientists continue to explore novel possibilities for selective S1P modulators. This study provides a concise overview of sphingolipid metabolism, the mechanism by which S1P receptors are af-fected, and the structural characteristics of several small molecule S1P modulators, with a particu-lar focus on their structure-activity connections.
{"title":"The Current Landscape in the Development of Small-molecule Modulators Targeting Sphingosine-1-phosphate Receptors to Treat Neurodegenerative Diseases","authors":"Sidharth Sankar Kar, Soumya Ranjan Gharai, Sujit Kumar Sahu, V. Ravichandiran, Sharada Prasanna Swain","doi":"10.2174/0115680266288509240422112839","DOIUrl":"https://doi.org/10.2174/0115680266288509240422112839","url":null,"abstract":": Sphingosine 1-phosphate (S1P) is extensively researched as a lysophospholipid and is crucial in various physiological and pathological processes. It achieves this via signalling through five different subtypes of G protein-coupled receptors (GPCRs), namely S1PR1 to S1PR5. S1PR modulators possess the ability to traverse the blood-brain barrier, potentially leading to direct ac-tions within the Central Nervous System (CNS). S1PR modulators specifically bind to receptors located on the surface of naive and central memory lymphocytes, causing these cells to be trapped or confined within the lymph node. The investigation of the S1P pathway has resulted in the ap-proval of three S1PR modulators, namely fingolimod, siponimod, and ozanimod, as medications for the treatment of patients suffering from Multiple Sclerosis (MS). Additionally, new S1PR modulators, such as ponesimod and etrasimod, are currently being developed and tested in clini-cal trials. Research on the creation of S1P modulators in neurodegenerative illnesses is ongoing as scientists continue to explore novel possibilities for selective S1P modulators. This study provides a concise overview of sphingolipid metabolism, the mechanism by which S1P receptors are af-fected, and the structural characteristics of several small molecule S1P modulators, with a particu-lar focus on their structure-activity connections.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"20 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27DOI: 10.2174/0115680266291290240417081544
Suleyman Ilhan, Ferdi Oguz, Harika Atmaca
:: Although immunotherapy and targeted therapy have radically changed melanoma treatment, the development of resistance and reduction of patient responses are still significant problems. Small molecule inhibitors are needed to overcome this situation, and biomarkers that can estimate whether patients will reply to existing treatments need to be developed. miRNAs are involved in diverse processes such as tumor development, tumor progression, metastasis, and invasion. While some miRNAs act as tumor suppressors, others may be oncogenic. miRNAs also contribute to the processes involved in drug resistance. There is increasing evidence demonstrating the possible effect of miRNAs on the diagnosis and treatment markers of melanoma. The manuscript focuses on the current challenges in melanoma treatment, highlighting issues such as the development of resistance and reduced patient responses despite the revolutionary advancements in targeted therapy and immunotherapy. It underscores the need for small molecule inhibitors and the creation of biomarkers for predicting patient responses to current treatments. The role of miRNAs in processes such as tumor development, metastasis, and invasion has been highlighted. While certain miRNAs function as tumor suppressors, others may exhibit oncogenic properties. Furthermore, increasing evidence is presented demonstrating the potential significance of miRNAs as markers for the symptom and identification of melanoma. These findings indicate a promising avenue for future research and clinical applications. In summary, the article effectively communicates key insights, making it a valuable resource for those interested in melanoma research and treatment.
{"title":"A New Approach to Melanoma Treatment: microRNAs","authors":"Suleyman Ilhan, Ferdi Oguz, Harika Atmaca","doi":"10.2174/0115680266291290240417081544","DOIUrl":"https://doi.org/10.2174/0115680266291290240417081544","url":null,"abstract":":: Although immunotherapy and targeted therapy have radically changed melanoma treatment, the development of resistance and reduction of patient responses are still significant problems. Small molecule inhibitors are needed to overcome this situation, and biomarkers that can estimate whether patients will reply to existing treatments need to be developed. miRNAs are involved in diverse processes such as tumor development, tumor progression, metastasis, and invasion. While some miRNAs act as tumor suppressors, others may be oncogenic. miRNAs also contribute to the processes involved in drug resistance. There is increasing evidence demonstrating the possible effect of miRNAs on the diagnosis and treatment markers of melanoma. The manuscript focuses on the current challenges in melanoma treatment, highlighting issues such as the development of resistance and reduced patient responses despite the revolutionary advancements in targeted therapy and immunotherapy. It underscores the need for small molecule inhibitors and the creation of biomarkers for predicting patient responses to current treatments. The role of miRNAs in processes such as tumor development, metastasis, and invasion has been highlighted. While certain miRNAs function as tumor suppressors, others may exhibit oncogenic properties. Furthermore, increasing evidence is presented demonstrating the potential significance of miRNAs as markers for the symptom and identification of melanoma. These findings indicate a promising avenue for future research and clinical applications. In summary, the article effectively communicates key insights, making it a valuable resource for those interested in melanoma research and treatment.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"5 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.
:阿尔茨海默病（AD）是神经退行性疾病（ND）中最常见的一种，截至 2023 年，全球有 4400 多万人罹患该病。其特征是认知功能障碍和无法进行日常活动。注意力缺失症的发展与淀粉样 beta（Aβ）的积累、神经纤维缠结（NFT）的形成、氧化应激增加、神经炎症、线粒体功能障碍和内质网应激有关。目前，已发现多种植物药及其生物活性化合物具有神经保护作用，可降低氧化应激、缓解神经炎症、减轻大脑海马区和大脑皮层中 Aβ 和乙酰胆碱酯酶的积累。然而，尽管植物成分具有良好的抗阿尔茨海默氏症效果，但其临床应用范围仍然有限。造成这种限制的关键因素是传统给药系统所固有的挑战，这些挑战阻碍了其有效性和效率。这些困难包括药物靶向性不足、药物溶解度和稳定性受限、作用时间短暂以及缺乏对药物释放的控制。因此，这些制约因素导致生物利用度降低，通过血脑屏障（BBB）的渗透性不足。为了应对这些挑战，以纳米制剂为基础的新型给药系统（NDDS）应运而生，成为提高溶解性差的生物活性化合物的生物利用度和血脑屏障渗透性的一种有希望的策略。在这些系统中，纳米乳剂（NE）因其在靶向抗逆转录病毒（AD）方面的潜力而受到广泛研究。纳米乳液具有制备简便、载药量高和稳定性强等优点。由于其为纳米级液滴，NE 还能改善肠道和 BBB 的通透性，从而提高药物在全身循环和大脑中的渗透性。各种研究都报道了在不同动物物种（包括转基因大鼠、Wistar 大鼠、Sprague-Dawley（SD）大鼠和小鼠）中测试 NE 植物成分及其生物活性的情况。然而，在注意力缺失症研究中，通常采用转基因小鼠来分析 Aβ 的影响。本综述讨论了各种植物成分的神经保护作用、与传统给药相关的挑战以及对 NDDS（尤其是 NE）的需求等各个方面。此外，还讨论了涉及基于植物成分的 NE 治疗注意力缺失症的各种研究。
{"title":"Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer’s Disease","authors":"Sukriti Vishwas, Bushra Bashir, Devendra Birla, Nikhil Khandale, Motamarri Venkata Naga Lalitha Chaitanya, Dinesh Kumar Chellappan, Gaurav Gupta, Poonam Negi, Kamal Dua, Sachin Kumar Singh","doi":"10.2174/0115680266296001240327090111","DOIUrl":"https://doi.org/10.2174/0115680266296001240327090111","url":null,"abstract":": Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"52 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.2174/0115680266300963240408051156
Lim Joe Siang, Harish Rajak, Veerasamy Ravichandran
The multifaceted benefits of Lepisanthes fruticosa position it is not only as a promising agricultural commodity but also as a versatile resource with implications for health, biodiversity, and economic growth. Lepisanthes fruticosa has a rich history of traditional use for treating various ailments such as fever and diarrhea. Beyond its traditional uses, the plant's antioxidant properties suggest potential applications in combating oxidative stress-related conditions. Its antihyperglycemic properties indicate promise in managing elevated blood sugar levels, while its antibacterial and antiviral attributes hint at potential applications in infectious disease control. Furthermore, the plant's anticancer properties add to its appeal as a valuable resource in the realm of medical research. The plant also exhibits considerable potential in addressing a range of health concerns, including non-communicable diseases and infections, antidiarrheal, and antiviral properties. In essence, Lepisanthes fruticose emerges as more than just an agricultural asset. Its unique combination of nutritional richness, health benefits, and economic viability underscores its potential to become a valuable asset both locally and on the global stage. In this current review, we are discussed about the ethnopharmacology, nutritional value, therapeutic effects, phytochemistry, and toxicology of Lepisanthes fruticose.
{"title":"Nutritional Value, Therapeutic Effects, Phytochemistry, and Toxicology of Lepisanthes fruticosa: A Review","authors":"Lim Joe Siang, Harish Rajak, Veerasamy Ravichandran","doi":"10.2174/0115680266300963240408051156","DOIUrl":"https://doi.org/10.2174/0115680266300963240408051156","url":null,"abstract":"The multifaceted benefits of Lepisanthes fruticosa position it is not only as a promising agricultural commodity but also as a versatile resource with implications for health, biodiversity, and economic growth. Lepisanthes fruticosa has a rich history of traditional use for treating various ailments such as fever and diarrhea. Beyond its traditional uses, the plant's antioxidant properties suggest potential applications in combating oxidative stress-related conditions. Its antihyperglycemic properties indicate promise in managing elevated blood sugar levels, while its antibacterial and antiviral attributes hint at potential applications in infectious disease control. Furthermore, the plant's anticancer properties add to its appeal as a valuable resource in the realm of medical research. The plant also exhibits considerable potential in addressing a range of health concerns, including non-communicable diseases and infections, antidiarrheal, and antiviral properties. In essence, Lepisanthes fruticose emerges as more than just an agricultural asset. Its unique combination of nutritional richness, health benefits, and economic viability underscores its potential to become a valuable asset both locally and on the global stage. In this current review, we are discussed about the ethnopharmacology, nutritional value, therapeutic effects, phytochemistry, and toxicology of Lepisanthes fruticose.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"18 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-15DOI: 10.2174/0115680266293212240405042540
Divya Adiga, Sangavi Eswaran, S Sriharikrishnaa, Nadeem G. Khan, Dileep Kumar, Shama Prasada Kabekkodu
: Alzheimer’s disease (AD) is a multifactorial disorder resulting from the complex interaction between genetic, epigenetic, and environmental factors. It represents an impending epidemic and lacks effective pharmacological interventions. The emergence of high throughput sequencing techniques and comprehensive genome evaluation has uncovered a diverse spectrum of non-- coding RNA (ncRNA) families. ncRNAs are the critical modulators of an eclectic array of biological processes and are now transpiring as imperative players in diagnosing and treating various diseases, including neurodegenerative disorders. Several ncRNAs are explicitly augmented in the brain, wherein they potentially regulate cognitive abilities and other functions of the central nervous system. Growing evidence suggests the substantial role of ncRNAs as modulators of tau phosphorylation, Aβ production, neuroinflammation, and neuronal survival. It indicates their therapeutic relevance as a biomarker and druggable targets against AD. The current review summarizes the existing literature on the functional significance of ncRNAs in AD pathogenesis and its imminent implications in clinics.
:阿尔茨海默病（AD）是一种多因素疾病，由遗传、表观遗传和环境因素之间复杂的相互作用引起。它是一种即将流行的疾病，缺乏有效的药物干预措施。高通量测序技术和全面基因组评估的出现，揭示了非编码 RNA（ncRNA）家族的多样性。ncRNA 是一系列生物过程的关键调节因子，目前正在成为诊断和治疗包括神经退行性疾病在内的各种疾病的重要角色。有几种 ncRNA 在大脑中明显增强，有可能调节认知能力和中枢神经系统的其他功能。越来越多的证据表明，ncRNA 在调节 tau 磷酸化、Aβ 生成、神经炎症和神经元存活方面发挥着重要作用。这表明它们作为一种生物标记物和抗抑郁药物靶点具有治疗意义。本综述总结了现有文献中关于 ncRNA 在 AD 发病机制中的功能意义及其对临床即将产生的影响。
{"title":"Noncoding RNAs in Alzheimer’s Disease: Overview of Functional and Therapeutic Significance","authors":"Divya Adiga, Sangavi Eswaran, S Sriharikrishnaa, Nadeem G. Khan, Dileep Kumar, Shama Prasada Kabekkodu","doi":"10.2174/0115680266293212240405042540","DOIUrl":"https://doi.org/10.2174/0115680266293212240405042540","url":null,"abstract":": Alzheimer’s disease (AD) is a multifactorial disorder resulting from the complex interaction between genetic, epigenetic, and environmental factors. It represents an impending epidemic and lacks effective pharmacological interventions. The emergence of high throughput sequencing techniques and comprehensive genome evaluation has uncovered a diverse spectrum of non-- coding RNA (ncRNA) families. ncRNAs are the critical modulators of an eclectic array of biological processes and are now transpiring as imperative players in diagnosing and treating various diseases, including neurodegenerative disorders. Several ncRNAs are explicitly augmented in the brain, wherein they potentially regulate cognitive abilities and other functions of the central nervous system. Growing evidence suggests the substantial role of ncRNAs as modulators of tau phosphorylation, Aβ production, neuroinflammation, and neuronal survival. It indicates their therapeutic relevance as a biomarker and druggable targets against AD. The current review summarizes the existing literature on the functional significance of ncRNAs in AD pathogenesis and its imminent implications in clinics.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"21 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140574018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
:: Biomarkers are the most significant diagnosis tools tending towards unique approaches and solutions for the prevention and cure of Alzheimer’s Disease (AD). The current report provides a clear perception of the concept of various biomarkers and their prominent features through analysis to provide a possible solution for the inhibition of events in AD. Scientists around the world truly believe that crucial hallmarks can serve as critical tools in the early diagnosis, cure, and prevention, as well as the future of medicine. The awareness and understanding of such biomarkers would provide solutions to the puzzled mechanism of this neuronal disorder. Some of the argued biomarkers in the present article are still in an experimental phase as they need to undergo specific clinical trials before they can be considered for treatment.
{"title":"Prominent Perspective on Existing Biological Hallmarks of Alzheimer’s Disease","authors":"Namrata Singh, Srishti Sharma, Kallol K. Ghosh, Bhanushree Gupta, Kamil Kuca","doi":"10.2174/0115680266292514240404040341","DOIUrl":"https://doi.org/10.2174/0115680266292514240404040341","url":null,"abstract":":: Biomarkers are the most significant diagnosis tools tending towards unique approaches and solutions for the prevention and cure of Alzheimer’s Disease (AD). The current report provides a clear perception of the concept of various biomarkers and their prominent features through analysis to provide a possible solution for the inhibition of events in AD. Scientists around the world truly believe that crucial hallmarks can serve as critical tools in the early diagnosis, cure, and prevention, as well as the future of medicine. The awareness and understanding of such biomarkers would provide solutions to the puzzled mechanism of this neuronal disorder. Some of the argued biomarkers in the present article are still in an experimental phase as they need to undergo specific clinical trials before they can be considered for treatment.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"12 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140574114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA muta-tions that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifi-cally mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mito-chondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structure-activity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the man-agement of neurodegenerative diseases associated with mitochondrial defects. This review pro-vides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.
:神经退行性疾病正在成为当前全球关注的健康问题，而它们与线粒体缺陷的关联一直是一个潜在的研究领域。线粒体是细胞的重要细胞器之一，是细胞的动力源，可产生能量并确保细胞健康。神经退行性疾病，如阿尔茨海默氏症、帕金森氏症、亨廷顿氏症、肌萎缩性脊髓侧索硬化症和佩利泽斯-默茨巴赫氏病，主要是由线粒体功能失调引发的。线粒体呼吸的主要副产物之一活性氧也是线粒体 DNA 变异的重要原因，最终导致线粒体崩溃。这篇综述论文全面探讨了治疗性生物大分子（尤其是线粒体特异性抗氧化剂）在减轻线粒体缺陷对神经退行性疾病的影响方面的潜力。本综述详细分析了线粒体功能障碍的相关机制、这些生物大分子的潜在治疗靶点以及它们的结构-活性关系信息。在汇编数据时广泛使用了各种研究文章和出版物，并使用 ChemDraw 和 ChemSketch 等软件制作了生物大分子结构。确定了引发线粒体异常的关键因素，并以表格形式汇编了生物活性抗氧化化合物及其治疗目标。线粒体特异性抗氧化疗法是治疗与线粒体缺陷有关的神经退行性疾病的一种创新且前景广阔的策略。这篇综述全面总结了这一领域的研究现状和有前景的研发途径，强调了进一步调查和临床试验以阐明其治疗功效的重要性。
{"title":"Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules","authors":"Tanmoy Roy, Swarupanjali Padhi, Rupa Mazumder, Chandana Majee, Saumya Das, Monika Monika, Rashmi Mishra, Bhupinder Kapoor","doi":"10.2174/0115680266299148240329062647","DOIUrl":"https://doi.org/10.2174/0115680266299148240329062647","url":null,"abstract":": Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA muta-tions that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifi-cally mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mito-chondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structure-activity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the man-agement of neurodegenerative diseases associated with mitochondrial defects. This review pro-vides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"3 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140574020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.2174/0115680266300736240403075307
Nursyuhada Azzman, Sirajudheen Anwar, Wan Ahmad Syazani Mohamed, Nafees Ahemad
:: Quinolone is a heterocyclic compound containing carbonyl at the C-2 or C-4 positions with nitrogen at the C-1 position. The scaffold was first identified for its antibacterial properties, and the derivatives were known to possess many pharmacological activities, including anticancer. In this review, the quinolin-2(H)-one and quinolin-4(H)-one derivatives were identified to inhibit several various proteins and enzymes involved in cancer cell growth, such as topoisomerase, mi-crotubules, protein kinases, phosphoinositide 3-kinases (PI3K) and histone deacetylase (HDAC). Hybrids of quinolone with curcumin or chalcone, 2-phenylpyrroloquinolin-4-one and 4-quinolone derivatives have demonstrated strong potency against cancer cell lines. Additionally, quinolones have been explored as inhibitors of protein kinases, including EGFR and VEGFR. Therefore, this review aims to consolidate the medicinal chemistry of quinolone derivatives in the pipeline and discuss their similarities in terms of their pharmacokinetic profiles and potential target sites to provide an understanding of the structural requirements of anticancer quinolones.
{"title":"Quinolone Derivatives as Anticancer Agents: Importance in Medicinal Chemistry","authors":"Nursyuhada Azzman, Sirajudheen Anwar, Wan Ahmad Syazani Mohamed, Nafees Ahemad","doi":"10.2174/0115680266300736240403075307","DOIUrl":"https://doi.org/10.2174/0115680266300736240403075307","url":null,"abstract":":: Quinolone is a heterocyclic compound containing carbonyl at the C-2 or C-4 positions with nitrogen at the C-1 position. The scaffold was first identified for its antibacterial properties, and the derivatives were known to possess many pharmacological activities, including anticancer. In this review, the quinolin-2(H)-one and quinolin-4(H)-one derivatives were identified to inhibit several various proteins and enzymes involved in cancer cell growth, such as topoisomerase, mi-crotubules, protein kinases, phosphoinositide 3-kinases (PI3K) and histone deacetylase (HDAC). Hybrids of quinolone with curcumin or chalcone, 2-phenylpyrroloquinolin-4-one and 4-quinolone derivatives have demonstrated strong potency against cancer cell lines. Additionally, quinolones have been explored as inhibitors of protein kinases, including EGFR and VEGFR. Therefore, this review aims to consolidate the medicinal chemistry of quinolone derivatives in the pipeline and discuss their similarities in terms of their pharmacokinetic profiles and potential target sites to provide an understanding of the structural requirements of anticancer quinolones.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"51 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05DOI: 10.2174/0115680266294573240328050629
Kok-Hou Yit, Zamirah Zainal-Abidin
Aim:: There has been increased scientific interest in bioactive compounds and their synthetic derivatives to promote the development of antimicrobial agents that could be used sustainably and overcome antibiotic resistance. Methods:: We conducted this scoping review to collect evidence related to the antimicrobial potential of diverse natural compounds from Zingiberaceae plants and their synthetic derivatives. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews guidelines. The literature search was conducted using PubMed, Web of Science and Scopus electronic databases for relevant studies published from 2012 to 2023. A total of 28 scientific studies fulfilled the inclusion criteria. The authors of these studies implemented in vitro and in silico methods to examine the antimicrobial potency and underlying mechanisms of the investigated compounds. Result:: The evidence elucidates the antimicrobial activity of natural secondary metabolites from Zingiberaceae species and their synthetic derivatives against a broad panel of gram-positive and gram-negative bacteria, fungi and viruses. Conclusion:: To date, researchers have proposed the application of bioactive compounds derived from Zingiberaceae plants and their synthetic analogues as antimicrobial agents. Nevertheless, more investigations are required to ascertain their efficacy and to broaden their commercial applicability.
{"title":"Antimicrobial Potential of Natural Compounds of Zingiberaceae Plants and their Synthetic Analogues: A Scoping Review of In vitro and In silico Approaches","authors":"Kok-Hou Yit, Zamirah Zainal-Abidin","doi":"10.2174/0115680266294573240328050629","DOIUrl":"https://doi.org/10.2174/0115680266294573240328050629","url":null,"abstract":"Aim:: There has been increased scientific interest in bioactive compounds and their synthetic derivatives to promote the development of antimicrobial agents that could be used sustainably and overcome antibiotic resistance. Methods:: We conducted this scoping review to collect evidence related to the antimicrobial potential of diverse natural compounds from Zingiberaceae plants and their synthetic derivatives. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews guidelines. The literature search was conducted using PubMed, Web of Science and Scopus electronic databases for relevant studies published from 2012 to 2023. A total of 28 scientific studies fulfilled the inclusion criteria. The authors of these studies implemented in vitro and in silico methods to examine the antimicrobial potency and underlying mechanisms of the investigated compounds. Result:: The evidence elucidates the antimicrobial activity of natural secondary metabolites from Zingiberaceae species and their synthetic derivatives against a broad panel of gram-positive and gram-negative bacteria, fungi and viruses. Conclusion:: To date, researchers have proposed the application of bioactive compounds derived from Zingiberaceae plants and their synthetic analogues as antimicrobial agents. Nevertheless, more investigations are required to ascertain their efficacy and to broaden their commercial applicability.","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":"66 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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