Current topics in medicinal chemistry最新文献

{"title":"A Review on Anticancer Potential and Structure-Activity Relationships (SAR) of Novel EGFR/HER2 Inhibitors.","authors":"Subhadip Maity, Priya Devi, Aastha Singh, Vikas Asati, Vivek Asati","doi":"10.2174/0115680266378477250610122156","DOIUrl":"https://doi.org/10.2174/0115680266378477250610122156","url":null,"abstract":"<p><p>Human Epidermal Growth Receptor (HER) plays an important role in cell signalling pathways and influences different cell functioning like angiogenesis, apoptosis, metastasis, and growth of cells. Their family includes four members with structural similarities, named EGFR/HER1, HER2, HER3, and HER4. Overexpression of these receptors is responsible for the development of cancer. EGFR/HER2 dual inhibitors, approved by the US FDA (Food and Drug Administration), include lapatinib, afatinib, neratinib, dacomitinib, etc., but these drugs lack selectivity, specificity, and undesirable adverse effects. The ultimate challenges in developing lead compounds for EGFR/HER2 dual inhibitors include achieving precision, and minimising toxicity and drug resistance. This inspires medicinal and organic chemists to design new molecules. The present manuscript focuses on the identification and development of therapeutic molecules that can inhibit the target proteins EGFR/HER2 and can further be used for the treatment of breast and lung malignancies. It also highlights the development of EGFR/HER2 dual inhibitors that belong to different structural classes like pyrimidine, quinazoline, pyridine, benzimidazole, and quinoline etc. Various parameters, such as Structure-Activity Relationships (SAR), clinical trials data, patent filed, and the molecular docking study of the most potent compounds provide a valuable asset for further designing and discovering new EGFR/HER2 dual inhibitors with potential therapeutic significances for cancer treatment.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505080","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":"Modern Approaches to Diabetes: The Role of Phytochemicals in Targeting Molecular Receptors.","authors":"Satyapriya Mahapatra, Ghanshyam Panigrani, Lorie Dehury, Anshuman Gouda, Diptirani Rath","doi":"10.2174/0115680266352449250612211106","DOIUrl":"https://doi.org/10.2174/0115680266352449250612211106","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus (DM) is a chronic metabolic disorder characterized by the impaired utilization of glucose, insulin resistance, or reduced insulin production. Although conventional pharmacologic agents like metformin, sulfonylureas, and thiazolidinediones are effective in regulating elevated blood glucose levels, they are often associated with some adverse effects, such as weight gain and liver problems. The present review summarizes the possibility of using phytochemicals as safer alternatives for the management of DM by modulation of molecular receptors.</p><p><strong>Methods: </strong>Several studies have reported that certain antioxidant phytochemicals exhibit inhibitory effects on key signaling pathways involved in glucose metabolism and insulin sensitivity under in vitro conditions. Therefore, this review will focus on the therapeutic potential of phytochemicals in modulating molecular targets, such as PPARs, GPR119, free fatty acid (FFA) receptors, glucocorticoid receptors, and others. For this purpose, a systematic and extensive literature search was carried out to obtain relevant data, focusing on the prospect of phytochemicals in modulating molecular receptors for diabetes mellitus (DM) management. Electronic databases, including Pub- Med, Scopus, ScienceDirect, and Google Scholar, were accessed for articles up to March 2025.</p><p><strong>Results: </strong>Curcumin, resveratrol, and quercetin are bioactive molecules that increase the sensitivity of the body to insulin and protect the pancreatic β-cells from oxidative stress. Natural agents, such as garlic, green tea, and blackcurrants, possess an antidiabetic action by inhibiting enzymes, such as α-glucosidase, and increasing the uptake of glucose. The co-administration of synthetic drugs along with natural agents has a synergistic effect in improving glycemic control with fewer side effects. Examples include resveratrol with metformin or curcumin with thiazolidinediones.</p><p><strong>Conclusion: </strong>The findings of this review should be validated at the clinical level in future research studies, including toxicity profiling and formulation optimization, to maximize the therapeutic potential of phytochemicals in the management of DM.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474203","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":"Benzoxathiolone-Thiazolidinone Hybrids: A New Class in the Search for Anticancer Agents.","authors":"Eliza de Lucas Chazin, Ligia Souza da Silveira Pinto, Victor Facchinetti, Paula de Aquino Soeiro Portilho, Breno de Souza Bernardes, Claudia Regina Brandão Gomes, Emerson Lucena da Silva, Luina Benevides Lima, Felipe Pantoja Mesquita, Pedro Filho Noronha de Souza, Raquel Carvalho Montenegro, Marcus Vinicius Nora De Souza, Thatyana Rocha Alves Vasconcelos","doi":"10.2174/0115680266366285250528005320","DOIUrl":"https://doi.org/10.2174/0115680266366285250528005320","url":null,"abstract":"<p><strong>Background: </strong>Cancer continues to be a significant public health issue and one of the leading causes of death globally. In this context, developing new, potent, and more specific treatments against this disease is urgent.</p><p><strong>Methods: </strong>A total of 15 benzoxathiolone-thiazolidinones hybrids were synthesized in a 5-step route and tested for their cytotoxicity against five human cancer cell lines: AGP-01 (gastric), SKMEL- 103 (melanoma), HCT-116 (colon), CAL27 (tongue), and K562 (leukemia), as well as a nontumoral cell line MRC-5.</p><p><strong>Results: </strong>Compounds 3-(6-hydroxy-2-oxobenzo[d][1,3]oxathiol-5-yl)-2-(4-nitrophenyl)thiazolidin- 4-one and 2-(2,4-dichlorophenyl)-3-(6-hydroxy-2-oxobenzo[d][1,3]oxathiol-5-yl)thiazolidin-4-one exhibited good activity against the K562 leukemia cell line, with IC50 values of 4.0 μM and 5.3 μM, respectively. Docking studies demonstrated that these compounds likely bind to the BCRABL1 kinase, a key protein in the pathogenesis of chronic myeloid leukemia (CML).</p><p><strong>Conclusion: </strong>The study suggests these benzoxathiolone-thiazolidinone hybrids could be promising lead compounds for developing new anticancer agents targeting leukemia.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324661","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":"Histone Deacetylase Inhibition in Alzheimer's Disease: Molecular Mechanisms, Therapeutic Potential, and Future Perspectives.","authors":"Nachiket Joshi, Prachee Khadse, Shivani Jadhav, RajaSekhar Reddy Alavala","doi":"10.2174/0115680266360664250606110220","DOIUrl":"https://doi.org/10.2174/0115680266360664250606110220","url":null,"abstract":"<p><p>Alzheimer's disease (AD) remains a formidable challenge in modern medicine, with limited therapeutic options available to combat its progressive cognitive decline. Histone acetylation is a key epigenetic mechanism responsible for gene expression, cell growth, and differentiation. HDAC is a group of enzymes that can reverse the acetylation of cells. These enzymes have been evidenced to be involved in the pathophysiology of AD. Hence, inhibition of this enzyme was postulated to exhibit pronounced benefits in AD concerning memory, learning, and cognition. Pan-HDAC inhibitors inhibited multiple HDAC isoforms but were associated with certain side effects. Hence, class-specific and isoform-specific inhibitors were discovered, revealing great potencies and proving efficacious. This review article comprehensively explores the evolving landscape of research avenues targeting HDAC inhibitors against AD. Beginning with the molecular mechanisms underlying AD pathology, we delve into the intricate roles of HDACs in neurodegeneration and synaptic dysfunction. Subsequently, we scrutinize preclinical studies investigating various HDAC inhibitors, elucidating their promising neuroprotective effects, modulation of epigenetic mechanisms, and potential for disease modification. Furthermore, we highlight the translational challenges and therapeutic opportunities in advancing HDAC inhibitors toward clinical applications for AD. By summarizing current research findings, this review aims to provide valuable insights into the burgeoning field of HDAC inhibition as a promising therapeutic strategy for combating AD, paving the way for future research directions and drug development endeavors.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324662","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":"Antibody-aptamer Complementation: Advancing Biosensing for Disease Monitoring.","authors":"Thangavel Lakshmipriya, Subash C B Gopinath","doi":"10.2174/0115680266372074250603091350","DOIUrl":"https://doi.org/10.2174/0115680266372074250603091350","url":null,"abstract":"<p><p>A biosensor is a biological device designed to convert biological responses into an electrical signal, which has diverse applications across various fields, including diagnostics, environmental monitoring, food safety, and drug discovery. Among these, biosensing technology has achieved remarkable success in medical diagnostics. To detect target molecules for various probe molecules, such as nucleic acids, peptides, antibodies, and proteins are widely used. Of these, antibodies are well-established as remarkable molecules for detecting and monitoring a broad range of analytes. Recently, a novel class of molecules known as aptamers, often referred to as \"artificial antibodies,\" has gained significant attention from researchers for numerous biomedical applications, particularly in biosensing. Aptamers are synthetic molecules generated through a method called Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Since aptamer and antibody have different bindings for target molecules, various biosensing techniques are utilized by using the combination of aptamer and antibody to enhance the biosensor. This combination possesses a unique and beneficial feature and holds the potential to drive significant advancements in sensing technology. Applying these combinations in biosensing technologies has some limitations due to the aptamer generation for some particular targets. This review explores recent applications of antibodies, aptamers, and their combined use in enhancing biosensing technologies and their limitations.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324660","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":"Qi Yin San Liang San Decoction Relieves Gefitinib-Induced Diarrhea via the Modulation of Chemokines and Innate Immune Responses.","authors":"Ke Yan, Qian Hua, Pengxiang Guo, Luyao Chen, Yufeng Chen, Haiyan Li, Xu Wang, Ya-Li Zhang, Yan Tan","doi":"10.2174/0115680266393963250611142026","DOIUrl":"https://doi.org/10.2174/0115680266393963250611142026","url":null,"abstract":"<p><strong>Background: </strong>Gefitinib is associated with various adverse reactions, with diarrhea being prevalent. It is mainly managed through lifestyle changes and symptomatic pharmacological interventions, but these approaches have limited effectiveness and frequent recurrence. Qi Yin San Liang San Decoction (QYSLS) shows promise in relieving gefitinib-induced diarrhea, but its mechanisms are unclear.</p><p><strong>Objective: </strong>This study aims to explore the pathological mechanisms underlying gefitinib-induced diarrhea and to elucidate the molecular pathways through which QYSLS mediates its therapeutic effects.</p><p><strong>Methods: </strong>RNA-seq identified differentially expressed genes (DEGs) in colon samples from control and gefitinib-induced diarrhea rats. Network pharmacology was employed to predict the bioactive components and potential targets of QYSLS. A protein-protein interaction (PPI) network was utilized to explore the interactions among these targets, while GO, KEGG, and GSEA enrichment analyses were conducted to reveal the signaling pathways associated with these targets. RNA-seq was used to detect DEGs in QYSLS-mediated relieving of gefitinib-induced diarrhea; the intersection with potential targets was further analyzed to identify key genes. The expression of hub genes was validated through immunohistochemistry and RT-qPCR.</p><p><strong>Results: </strong>RNA-seq and network pharmacology identified 103 bioactive components of QYSLS, with 84 potential targets in QYSLS relieving gefitinib-induced diarrhea. The DEGs in QYSLS relieving gefitinib-induced diarrhea and 84 potential targets were intersected, resulting in the identification of 26 key genes. Further analysis highlighted three central hub genes (CCL20, CCL25, NOS2), which were enriched in pathways related to innate immune response. Furthermore, immunohistochemistry and RT-qPCR confirmed that the expression of CCL25 was reduced by QYSLS in gefitinib-induced diarrhea rats.</p><p><strong>Conclusion: </strong>These results indicate that QYSLS may exert its therapeutic effect on gefitinibinduced diarrhea via the modulation of chemokines and innate immune responses.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316154","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":"The Green Synthesis of Cu Nanoparticles and Investigation of the Antibacterial Properties and Cytotoxicity on Multidrug-Resistant E. coli.","authors":"XiaoFeng Yuan, Yu Wang","doi":"10.2174/0115680266379834250605135159","DOIUrl":"https://doi.org/10.2174/0115680266379834250605135159","url":null,"abstract":"<p><strong>Introduction: </strong>Although E. coli is considered a normal human microbiota, it may cause life-threatening infections such as septicemia, urinary tract infections, and enteric infections. Moreover, multidrug-resistant strains are a serious challenge in the clinic due to high mortality rates and the limited number of therapeutic options. Hence, the current study aimed to benefit from pink rose petals as a source of green synthesis of copper nanoparticles (Cu-NPs), to investigate the antibacterial features against multidrug-resistant E. coli, and to measure the cytotoxicity of Cu-NPs.</p><p><strong>Methods: </strong>Pink rose petals were used as a reducing agent for Cu-NP synthesis, and then XRD, zeta potential, UV-Vis, FTIR, SEM, and DLS analyses were performed to characterize the synthesized NPs. Moreover, the MIC and zone of inhibition values of Cu-NPs were measured and compared to common antibiotics. Additionally, the MTT assay was performed to assess the cytotoxicity.</p><p><strong>Results: </strong>The green synthesized Cu-NPs were spherical and uniform with a size of ~200 nm. The MIC of Cu-NPs was 1024 μg/ml on the MDR strain of E. coli, representing the antibacterial activity comparable to levofloxacin (p-value>0.05) but less than imipenem and trimethoprim (pvalue< 0.001). Moreover, the CC50 of synthesized Cu-NPs was 731.2 μg/ml and significantly lower than the studied antibiotics (p-value<0.001).</p><p><strong>Conclusion: </strong>The findings may suggest Cu-NPs as a promising antibacterial strategy against MDR strains of E. coli, however, further studies are encouraged to clarify the safety of optimized doses.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316158","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 Review of Research from 2012 to 2024 on Pyrazole-based Anticancer Agents with SAR Study.","authors":"Deepali Wanode, Deweshri Nandurkar, Megha Ambatkar, Nilesh Rarokar, Pramod Khedekar","doi":"10.2174/0115680266370083250530180225","DOIUrl":"https://doi.org/10.2174/0115680266370083250530180225","url":null,"abstract":"<p><p>The field of cancer research has witnessed a surge in the exploration of novel therapeutic agents, with pyrazole derivatives emerging as promising candidates in the quest for effective anticancer treatments. This comprehensive review provides an in-depth analysis of the research landscape surrounding pyrazole derivatives as potential anticancer agents over the period from 2012 to 2024. Many synthetic pyrazole derivatives have been approved by the FDA and used as chemotherapeutic medicines, and some are under clinical trials, also reported in this article. The review aims to serve as a valuable resource for researchers, guiding future investigations and fostering the development of innovative pyrazole-based anticancer therapeutics.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282768","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":"Traditional Medicinal Food for Stress and Cancer Intervention.","authors":"Vijay Rani Rajpal, Renu Wadhwa, Sunil Kaul","doi":"10.2174/0115680266413093250604073402","DOIUrl":"https://doi.org/10.2174/0115680266413093250604073402","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282769","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":"Cancer-associated Fibroblasts (CAFs)-derived Exosomes Regulating Chemoresistance.","authors":"Gyas Khan, Md Sadique Hussain","doi":"10.2174/0115680266384380250603112353","DOIUrl":"https://doi.org/10.2174/0115680266384380250603112353","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257554","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}