Current topics in medicinal chemistry最新文献

{"title":"Drug Development Studies Targeting Neurological Disorders, Particularly Alzheimer's Disease.","authors":"Suleyman Akocak, Mehmet Boga, Anil Yilmaz","doi":"10.2174/0115680266435191250828105700","DOIUrl":"https://doi.org/10.2174/0115680266435191250828105700","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999943","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}

{"title":"Natural-Derived Products and Nanomaterials for the Treatment of Cancer and Chronic Disorders (Part 1).","authors":"Masoud Najafi","doi":"10.2174/0115680266433261250821081843","DOIUrl":"https://doi.org/10.2174/0115680266433261250821081843","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946131","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}

{"title":"Amarogentin, Natural Bitter Terpenoids: Research Update with Pharmacological Potential, Patent and Toxicity Aspects.","authors":"Sonia Singh, Mahima Varshney, Himanshu Sharma","doi":"10.2174/0115680266392073250808110715","DOIUrl":"https://doi.org/10.2174/0115680266392073250808110715","url":null,"abstract":"<p><p>Amarogentin is a secoiridoid glycoside that was initially isolated from the medicinal plant Swertia chirayita. It is well-known for its formidable bitter characteristics and the varied pharmacological actions it possesses. Especially in both conventional and modern medical practices, this molecule has garnered considerable attention due to its enormous therapeutic potential. Amarogentin possesses a wide range of biological actions, some of which include functions that are hepatoprotective, anti-inflammatory, anti-cancer, anti-diabetic, and antibacterial. The hepatoprotective function it possesses is achieved by enhancing antioxidant defense systems and reducing liver damage caused by toxins. It is believed that the ability of amarogentin to block proinflammatory mediators, such as TNF-α and IL-6, is responsible for its anti-inflammatory properties. The stimulation of apoptosis and the reduction of cancer cell proliferation in various tumor models are two additional ways in which it demonstrates promising anti-cancer potential. The antidiabetic activity of amarogentin is characterized by the modification of glucose metabolism as well as an improvement in insulin sensitivity. To enhance the therapeutic efficacy of amarogentin, further research is needed to investigate its bioavailability and stability in the human body. This is despite the fact that it possesses a wide range of pharmacological advantages. There are formulation options that could improve its pharmacokinetic profile. Some examples of these strategies are nanoparticle delivery systems and derivatization. In general, amarogentin exhibits a great deal of promise as a natural therapeutic agent for the treatment of liver diseases, cancer, and metabolic disorders. Accordingly, there is a need for further research into the mechanisms underlying its clinical applications and potential uses.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946162","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}

{"title":"Comprehension of the Function of Antioxidants in Targeting Different Signaling Pathways to Cure Oxidative Stress-Induced Hepatotoxicity.","authors":"Kartik Jadon, Swarupanjali Padhi","doi":"10.2174/0115680266398364250811231140","DOIUrl":"https://doi.org/10.2174/0115680266398364250811231140","url":null,"abstract":"<p><p>Oxidative stress plays a central role in the pathogenesis of liver diseases, including hepatotoxicity, by disrupting the balance between reactive oxygen species (ROS) and the hepatic antioxidant defense system. Excessive ROS production leads to inflammation, fibrosis, and cellular damage. Antioxidants-both endogenous and exogenous-can mitigate these effects by neutralizing ROS and restoring redox homeostasis. This review evaluates the mechanistic role of antioxidants in modulating key oxidative stress-related signaling pathways, such as nuclear factor erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), nuclear factorkappa B (NF-κB), phosphoinositide 3-kinase/Akt (PI3K/Akt), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). Through the regulation of these pathways, antioxidants reduce apoptosis, suppress pro-inflammatory signaling, and enhance the expression of detoxifying enzymes. Natural compounds like flavonoids, polyphenols, and vitamins C and E have shown hepatoprotective effects, while synthetic antioxidants and their combinations with other therapeutic agents represent promising strategies for clinical application. This review underscores the therapeutic potential of antioxidants in combating oxidative stress-induced hepatotoxicity by offering a comprehensive overview of their mechanistic targets.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946158","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}

{"title":"Druggable Targets in Zika Virus: A Systematic Review of Therapeutic Opportunities in Brazil.","authors":"Washington Kleber Rodrigues Lima, Claudia Zeneida Gomes Parente Alves Lima, Víctor Kleber Gomes Parente Alves Lima, Willian Reis Rosário, Lidio Gonçalves Lima-Neto, Maria Tereza Dos Santos Correia, Glaucio Monteiro Ferreira, Luís Cláudio Nascimento da Silva","doi":"10.2174/0115680266388856250811094000","DOIUrl":"https://doi.org/10.2174/0115680266388856250811094000","url":null,"abstract":"<p><strong>Introduction: </strong>Zika virus (ZIKV), a flavivirus primarily transmitted by Aedes aegypti, became a major global health concern during the 2015-2016 outbreak, particularly in Brazil. Its association with congenital malformations and neurological disorders underscores the urgent need for effective therapeutic interventions. This review explores molecular targets for ZIKV treatment within the Brazilian context.</p><p><strong>Method: </strong>A systematic search was conducted using PubMed, ScienceDirect, and Scopus for studies published between 2004 and 2024. Inclusion criteria focused on studies identifying druggable molecular targets related to viral replication, immune evasion, or host-virus interactions. Key search terms included \"Zika virus,\" \"molecular targets,\" \"Brazil,\" \"antiviral,\" and \"drug discovery.\"</p><p><strong>Results: </strong>The review identified several critical viral proteins, NS1, NS3, NS5, and the envelope protein, as potential drug targets. Host cellular factors essential for viral survival were also highlighted. Technologies such as high-throughput screening, molecular docking, and structural genomics contributed significantly to the identification and validation of these targets.</p><p><strong>Discussion: </strong>Although promising targets have been identified, therapeutic development is hindered by the genetic variability of ZIKV and its antigenic similarity to other flaviviruses, notably the dengue virus. These challenges complicate the specificity and efficacy of drugs. Nevertheless, Brazil has made strides in research infrastructure and collaborations to tackle these obstacles.</p><p><strong>Conclusion: </strong>This review synthesizes current knowledge on ZIKV molecular targets and ongoing drug discovery efforts. The findings support the strategic development of antivirals and emphasize the necessity for sustained investment in research to mitigate future ZIKV outbreaks in Brazil and globally.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946122","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}

{"title":"Unlocking the Multifunctional Therapeutic Potential of Manassantin: A Lignan-Derived Scaffold.","authors":"Navin Kumar Tailor","doi":"10.2174/0115680266389940250812105153","DOIUrl":"https://doi.org/10.2174/0115680266389940250812105153","url":null,"abstract":"<p><p>Manassantin, a dineolignan, is a natural compound that has gained significant attention due to its diverse pharmacological properties, including anti-inflammatory, anticancer, neuroprotective, and antimicrobial effects. Its unique polyphenolic scaffold offers a versatile platform for drug development, enabling targeted therapeutic applications. This review explores the molecular mechanisms underlying the bioactivity of manassantin with a focus on its role in modulating key cellular pathways, including NF-κB, MAPK, JAK/STAT, oxidative stress, apoptosis, and inflammatory signaling. Furthermore, it highlights recent advancements in structural modifications aimed at enhancing the pharmacokinetic and pharmacodynamic properties of this compound. By unlocking the full therapeutic potential of manassantin, this study paves the way for its future development as a multifunctional therapeutic agent.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946120","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}

{"title":"In Silico and In Vivo Hepatorenal Protective Effect of Chitosan-Loaded Chrysin Nanoparticles in Obese Rats.","authors":"Tahani Younis Omar, Saja Mohammad Al-Mosaidyyen, Esraa Nasser Mohammed, Nada Alaa Saied, Fatma Alzhraa Ayman, Juliana Kamal Khalil, Abdeljalil Mohamed Al Shawoush, Ayman Saber Mohamed","doi":"10.2174/0115680266388484250807033921","DOIUrl":"https://doi.org/10.2174/0115680266388484250807033921","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity, a widespread health condition marked by excessive body fat, markedly elevates the risk of chronic diseases and has emerged as a major global health issue. Chrysin, a flavonoid with promising health benefits, exhibits potent antioxidant and antiinflammatory properties. This study seeks to examine the impact of chitosan chrysin nanoparticles (Chrysin-CSNPS) on obesity induced by a high-fat diet (HFD) in male rats.</p><p><strong>Methods: </strong>Rats were fed a high-fat diet for 4 weeks to induce obesity, followed by a 4-week treatment period. Thirty rats were allocated into five groups (six rats per group): control (dist. water, orally), HFD control (dist. water, orally), HFD + chrysin (500 mg/kg, orally), HFD + chitosan-NP (60 mg/kg, orally), and HFD + Chrysin-CSNPS (60 mg/kg, orally).</p><p><strong>Results: </strong>In silico studies revealed that chrysin has a binding energy value of -8.8 kcal/mol to fat mass and obesity-associated (FTO) protein. Also, Chrysin is identified as an inhibitor of several cytochrome P450 enzymes, specifically CYP1A2, CYP2D6, and CYP3A4. Albumin, high-density lipoprotein cholesterol, glutathione, and nitric oxide levels rose, whereas glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, urea, total cholesterol, triglycerides, malondialdehyde, and nitric oxide levels fell upon Chrysin-CSNPS treatment. The histological examination revealed a significant enhancement in the structures of the liver and kidneys.</p><p><strong>Discussion: </strong>These findings suggest that chrysin could potentially inhibit FTO activity, thereby contributing to a reduction in obesity-related phenotypes. The compound that satisfied Lipinski's criteria was selected for toxicity prediction.</p><p><strong>Conclusion: </strong>Chrysin-CSNPS have hypolipidemic properties and an antioxidant role, reducing HFD consequences in the liver and kidney.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946085","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}

{"title":"UPLC-LCMS-Based Method Development, Validation, Forced Degradation, and Impurity Profiling of Nirogacestat Drug Substance.","authors":"S R Thrinath, Manikandan Krishnan, K S Lakshmi, Sharad D Mankumare","doi":"10.2174/0115680266407776250811045805","DOIUrl":"https://doi.org/10.2174/0115680266407776250811045805","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;This study aims to establish a novel, straightforward, and reliable UPLCMS method for determining the stability and impurity profile of Nirogacestat under various stress conditions, in accordance with ICH guidelines. The stability of Nirogacestat was investigated under various stress conditions, including acid/base hydrolysis, oxidation (H2O2), photolysis, reduction, and thermal degradation. This research addresses the need for a validated, stability-indicating method that performs reliably across key analytical parameters, thereby contributing to pharmaceutical quality assurance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Stress testing was performed by exposing Nirogacestat to various degradation conditions, including acid (0.1 and 1N HCl), base (NaOH), oxidative (30% H₂O₂), thermal (105°C), photolytic, and reductive environments. The mobile phase consisted of acetonitrile and 0.1% triethylamine/formic acid, adjusted to pH 2.5 in a 30:70 (v/v) ratio. Chromatographic separation was achieved using an Acquity UPLC BEH Shield RP-18 column (50 × 1.0 mm, 1.7 μm), with a flow rate of 0.5 mL/min and detection at 251 nm. Linearity was evaluated over a concentration range of 0.25 to 1.5 μg/mL. Validation studies assessed parameters such as selectivity, linearity, accuracy, precision, robustness, and solution stability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The method demonstrated excellent linearity (r² = 0.999), with peak area directly proportional to concentration within the studied range. All validation parameters were within acceptable limits. Forced degradation studies revealed distinct degradation products under each stress condition. Notably, alkaline degradation resulted in the least degradation, while acid, peroxide, photolytic, thermal, and reductive conditions produced a variety of degradation products. These were effectively separated from Nirogacestat using the developed method. The relative retention times for Nirogacestat and its impurities remained consistent, and mass spectrometry confirmed the identities of the degradation products.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The validated UPLC-MS method exhibited high sensitivity, selectivity, and robustness in detecting Nirogacestat and its impurities. It effectively distinguishes degradation products even within complex matrices and fully complies with ICH guidelines for analytical method validation. The degradation profile of Nirogacestat under various stress conditions provides critical insights into its stability behavior, which is essential for formulation development and regulatory compliance. The successful separation and identification of degradation products further underscore the method's applicability as a stability-indicating assay.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The developed UPLC-MS method is the first validated stability-indicating technique for Nirogacestat, offering comprehensive impurity profiling. It is precise, accurate, linear, and robust","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946171","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}

{"title":"Decoding Dementia Mechanisms: Identification of Key Oligodendrocyte-Associated Genes through Integrative Bioinformatics and Machine Learning.","authors":"Yan Chen, Hao Wen, Xinyi Qiu, Chen Li, Yinhui Yao, Yazhen Shang","doi":"10.2174/0115680266384153250804110312","DOIUrl":"https://doi.org/10.2174/0115680266384153250804110312","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to elucidate the mechanisms underlying Dementia using bioinformatics analysis and machine learning algorithms, to identify novel therapeutic targets for its clinical management.</p><p><strong>Methods: </strong>Gene expression datasets related to dementia were sourced from the GEO database. Differentially expressed genes (DEGs) were identified using R, and key module genes were determined through the Weighted Gene Co-expression Network Analysis (WGCNA) method. Oligodendrocyte (OL) related targets were retrieved from the GeneCards database. The intersecting genes from DEGs, WGCNA, and OL were analyzed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Subsequently, three machine learning algorithms were employed to pinpoint core genes associated with OL in dementia. The CIBERSORT algorithm was used to evaluate the abundance of 22 immune cell types and their correlation with Dementia-related immune infiltration. Validation was carried out via quantitative reverse transcription polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>Through bioinformatics and machine learning techniques, six core OL genes associated with Dementia were identified, notably C1QA, CD163, and TGFB2, which showed elevated expression in Dementia. Immune cell infiltration analysis indicated that several immune cell types may contribute to Dementia's pathogenesis, and RT-qPCR results corroborated the bioinformatics findings.</p><p><strong>Discussion: </strong>The discovered genes may contribute to dementia pathogenesis through oligodendrocyte dysfunction and neuroimmune interactions. Notably, TGFB2 and complement-related genes (C1QA, CD163) suggest involvement in both myelination defects and neuroinflammation, highlighting their therapeutic potential.</p><p><strong>Conclusion: </strong>The six feature genes: TGFB2, C1QA, CD163, ACTG1, WIF1, and OPALIN are significantly linked to Dementia.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854875","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}

{"title":"A Structure-activity Relationship (SAR) Insight for the Most Effective Oral Antidiabetic Compounds-A Current Review.","authors":"Fathiy Mutalabisin, Nader Ghaffari Khaligh","doi":"10.2174/0115680266379581250804035449","DOIUrl":"https://doi.org/10.2174/0115680266379581250804035449","url":null,"abstract":"<p><p>Diabetes mellitus, a chronic metabolic disorder, poses a significant global health challenge, demanding continuous research into effective treatments. With projections of 629 million individuals affected by 2045 and escalating healthcare costs, the need for new anti-diabetic medications is urgent. Current therapies often present limitations, including undesirable side effects and insufficient long-term efficacy. This review explores the development of oral anti-diabetic drugs (OADs), focusing on the structure-activity relationship (SAR) employed to create both established and emerging classes of medications. We examine the six major OAD classes: biguanides, sulfonylureas, meglitinides, thiazolidinediones, DPP-4 inhibitors, and SGLT2 inhibitors. In addition, a new promising class of OAD, namely metal complexes, is discussed. This review highlights the crucial role of synthetic chemistry in advancing diabetes treatment and improving patient outcomes.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854874","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}